Wound Masterclass - March 2024

Volume 3: Issue 8 - March 2024

woundmasterclass.com Open Access | Peer Reviewed | International | Quarterly ISSN 2753-6963

Paradigm Shift in Wound Care: Exploring the Bioactive Option

How can a Biodegradable Matrix Offer Limb-Saving Option for Chronic Ischemia?

Can Bioactive Glass Wound Matrix be Used to Facilitate Pain Reduction and Healing?

Complex Refractory Wounds: How to Overcome Treatment Recalcitrance Dermal Repair Powder: A New Option to Manage Irregular Wounds How to Optimise Healing of Hard-to-Heal Ulcers in Geriatric patients

Masterclass GUIDES

Bioactive Glass Wound Matrix

M.O.I.S.T. Concept

Wound Irrigation and Gel

Hydradenitis Suppuritiva

Mode of Action Electrical Stimulation

Official Journal of the Association for the Advancement of Wound Care®

Editorial Board

United Kingdom & Europe Dr Negin Shamsian

Prof Dimitri Beeckman

Dr Przemysław Lipiński

Prof Dr C. Can Cedidi

Dr Guido Ciprandi

Consultant Plastic & Reconstructive Surgeon (Locum)

Professor of Nursing Science, Ghent University (Belgium) and Vice-Head of the School of Health Sciences, Örebro University (Sweden)

Wound Surgeon, National Representative of Poland in D-Foot International

Clinic Director for Plastic, Reconstructive & Aesthetic Surgery

Professor of Wound Care at the Universities of Rome, Pavia, Turin, Trieste and Pisa

Łódź, Poland

Bremen, Germany

Specialist in thoracic surgery and pediatric surgery

Chief Editor of Wound Masterclass

Ghent, Belgium

London, United Kingdom

Rome, Italy

Dr Paul Chadwick

Mr Harm Jaap Smit

Ms Lian Stoeldraaijers

Prof Declan Patton

Dr Kirsi Isoherranen

National Clinical Director, Royal College of Podiatry

Wound Biologist, Erasmus MC Academy Rotterdam

President, Dutch Association of Diabetes Podiatrists

Rotterdam, Netherlands

Valkenswaard, Netherlands

Specialist in Dermatology, HUS Helsinki Wound Healing Centre

Manchester, United Kingdom

Director of Nursing and Midwifery Research and Deputy Director of SWaT Research Center, RCSI University of Medicine and Health Sciences Dublin, Ireland

Prof Jan Kottner

Prof Dr Luca Dalla Paola

Dr Sebastian Probst

Prof Dr Marco Romanelli

Professor of Nursing Science, Charité - Berlin University of Medicine

Specialist in Endocrinology, Metabolic Diseases and Diabetology

EWMA President

Berlin, Germany

Expert in medical and surgical treatment of Diabetic Foot

Full Professor and Chairman, Division of Dermatology, Department of Clinical and Experimental Medicine, University of Pisa

Ferrara, Italy

Professor of Tissue Viability and Wound Care at the School of Health Sciences, University of Applied Sciences and Arts Western Switzerland, Geneva

Pisa, Italy

Genf, Switzerland

North America Mr Frank Aviles

Dr M. Mark Melin

Dr Leo Nherera

Dr Brandon Bosque

Wound Care Clinical Coordinator, Natchitoches Regional Medical Center

Medical Director of the M Health Wound Healing Institute

Director, Global Head of Health Economics & Outcomes Research

Foot and Ankle Surgeon

Natchitoches LA, United States

Adjunct Associate Professor, University of Minnesota Surgical Department

Fort Worth TX, United States

Philadelphia PA, United States

Mineapolis MN, United States

Dr Mitch Sanders

Prof David Armstrong

Dr Aliza Lee

Dr Alton R. Johnson

CSO and EVP Alira Health.

CEO of WoundForce Inc. and Firefly Innovations LLC.

Professor of Surgery and Director, Southwestern Academic Limb Salvage Alliance (SALSA), Keck School of Medicine of USC

Clinical Research Investigator, Department of Veterans Affairs

Podiatric Surgeon

Salem VA, United States

Ann Arbor MI, United States

Boston MA, United States

Los Angeles CA, United States

Dr Jonathan Johnson

Dr David Alper

Dr Ruth Bryant

Surgical Director, Comprehensive Wound Care Services

Trustee - Board of Trustees, American Podiatric Medical Association

Nurse Scientist and WOC nurse, Abbott Northwestern Hospital

Board Member - American Diabetes Association (New England)

Washington DC, United States

Surgical staff (Emeritas) - Mount Auburn Hospital Cambridge, MA, United States

Minneapolis MN, United States

Boston MA, United States

Ms Kara Couch

Dr Kenneth Burhop

Mr Tobe Madu

President-Elect, Association for the Advancement of Wound Care

Life Sciences Advisor and Consultant

Data Scientist, Net Health

Associate Research Professor of Surgery, School of Medicine and Health Studies George Washington University

San Diego CA, United States

Atlanta GA, United States

Director, Wound Care Services, The George Washington University Hospital

Arlington VA, United States

East Asia

Australia

South & Central America

Dr Joon Pio Hong

Dr Ross D Farhadieh

Professor of Plastic and Reconstructive Surgery at the University of Ulsan College of Medicine and Asan Medical Center

Cosmetic Plastic & Reconstructive Surgeon Sydney, Australia

Prof Dr Harikrishna K. R. Nair President Elect, WUWHS - World Union of Wound Healing Societies

Ms Terry Swanson

Dr Eduardo Camacho

Vice Chair, International Wound Infection Institute

Plastic and Reconstructive Surgeon

Victoria, Australia

Mexico City, Mexico

President, Asia Pacific Association of Diabetic Limb Problems Kuala Lumpur, Malaysia

Dr Honda Hsu Plastic Surgeon and Associate Professor, Tzu Chi General Hospital Hualien, Taiwan

Middle East Sr Trish Idensohn

Prof Amit Gefen

Wound Nurse Specialist, Consultant and Educator

Professor of Biomedical Engineering, Tel Aviv University

Durban, South Africa

Head and Neck Surgeon, Associate Professor Instituto Universitario Hospital Italiano Buenos Aires, Argentina

Seoul, South Korea

Africa

Dr Luis Alejandro Boccalatte

Tel Aviv, Israel

Wound Care Physician

President of EWMA Helsinki, Finland

March 2024

Chief Editor Miss Negin Shamsian Commercial Director Mr Alec Wright Contact Editor editor@woundmasterclass.com

Commercial Inquiries commercial@woundmasterclass.com

Article Submissions submissions@woundmasterclass.com

Published by Clarus Communications Ltd., Oxford, United Kingdom No part of this issue is to be copied or reproduced without permission of the publisher © Clarus Communications Ltd.

This publication is intended for online distribution and this issue is not suitable for print in this form To inquire about obtaining a printable version of this issue or any article therein, please contact the editor

Harnessing the Power of Bioactive Wound Care: Unlocking the Potential for Accelerated Healing | Dr Negin Shamsian Advancing Regional Efforts Against Antimicrobial Resistance in the Americas: The Imperative for Collaborative Action | Dr Negin Shamsian Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds | Dr Donald W. Buck II, Dr Steven Jung How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Ischemia? | Ms Victoria Bristow Complex Refractory Wounds: How to Overcome Treatment Recalcitrance and Restore the Healing Trajectory Using Innovative Bioactive Glass | Dr Elvis Castillo Garcia, Dr Phuong Thuy Nguyen Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing for Patients with Pyoderma Gangerosum Ulcers? | Dr Luis A. Laurentin-Perez, Dr Donald W. Buck II, Mr Dagoberto Rivera Dermal Repair Powder: A New Option to Manage Irregular Wounds | Prof Dr Luca Dalla Paola How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers in Geriatric Patients with Multiple Comorbidities? | Dr Martin L. Johnson, Ms Erianthe Ortega, Prof David G. Armstrong How to Reduce Treatment Costs for Hard-to-Heal Wounds: The Bioactive Glass Wound Matrix Option| Dr P Rathinasamy, Dr JC Beckford MasterSeries 60 Minutes Interactive: DFU Masterclass MasterSeries 60 Minutes Interactive Convexity Masterclass Bioelectric Stimulation, Electric Fields and the Current of Injury: Have We Been Overlooking One of the Most Important Coordinators of the Wound Healing Process? | Dr Robin Martin

Cover image:

Masterclass GUIDES

MOIST Concept Bioactive Glass Wound Matrix Hydradenitis Suppuritiva

Licenced from Adobe Stock Credit: pinkeyes

Mode of Action: Electrical Wound Stimulation

0-0 0-0 0-0 0-0

Randomised self-controlled trial published in the International Wound Journal

The geko™ device reduces pain1 and doubles the rate of healing in venous leg ulcers versus compression alone2 VLUs affect one in 500 adults in the UK 3, costing the national healthcare system around £2 billion annually3

The study compared standard of care with and without the geko™ device in patients with hard-to-heal VLUs2

Reduces pain1 Accelerates healing2 Improves concordance5 Now available on prescription

VLUs, venous leg ulcers.

1. Jones N et al. Br J Nurs 2018; 27(20): S16-S21. 2. Bull, RH, Clements, D, Collarte, AJ, Harding, KG. The impact of a new intervention for venous leg ulcers: A withinpatient controlled trial. Int Wound J. 2023; 1- 9. doi:10.1111/iwj.14107. 3. Phillips, CJ, Humphreys, I, Thayer, D, et al. Cost of managing patients with venous leg ulcers. Int Wound J. 2020; 17: 1074– 1082. https://doi.org/10.1111/iwj.13366. 4. Das S et al. Int Wound J 2021; 18(2): 187-93. 5. Harris et al. Evaluation of a muscle pump-activating device for non-healing venous leg ulcers 2017. Medicalhelplines.com Inc and John Wiley & Sons Ltd doi: 10.1111/iwj.12784.

www.gekodevices.com MADWND0700v3

The geko™ device, a neuromuscular electrostimulator, increases venous, arterial and microcirculatory blood flow1, transporting oxygenated blood to the wound bed accelerating wound healing4

Harnessing the Power of Bioactive Wound Care: Unlocking the Potential for Accelerated Healing Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum. voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.

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Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.

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© Copyright. Wound Masterclass. 2024

qui officia deserunt mollit anim id est laborum.

Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.

Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.

Ut enim ad minim veniam, quis nostrud Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum. Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Ut enim ad minim veniam, quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat. Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur. Excepteur sint occaecat cupidatat non proident, sunt in culpa qui officia deserunt mollit anim id est laborum.

Dr Negin Shamsian Consultant Plastic & Reconstructive Surgeon (Locum) Chief Editor of Wound Masterclass London, United Kingdom

Wound Masterclass - Vol 3 - March 2024

3

Advancing Regional Efforts Against Antimicrobial Resistance in the Americas: The Imperative for Collaborative Action Editorial Summary Antimicrobial Resistance (AMR) is a formidable challenge that transcends national borders.

This editorial explores the current state of AMR surveillance in the Americas, shedding light on regional initiatives, policy responses, and the broader implications for global health.

Introduction

I

n the realm of contemporary global health concerns, few issues rival the gravity of antimicrobial resistance (AMR). With the potential to claim a staggering 10 million lives annually by 2050, according to the Review on Antimicrobial Resistance, AMR stands as a formidable challenge that transcends national borders. While initial skepticism surrounded these alarming predictions, recent studies, including a global burden of AMR research, have validated these concerns. Moreover, the establishment of data-backed strategies has become essential to address the impending catastrophe. The focus of this editorial is to delve into the current state of AMR surveillance in the Americas, shedding light on regional initiatives, policy responses, and the broader implications for global health.

Historical Footprint of AMR Surveillance

Dr Negin Shamsian Consultant Plastic & Reconstructive Surgeon (Locum) Chief Editor of Wound Masterclass

1

Steering through the annals of time, we find that the roots of AMR surveillance in the Americas run deep. Over 3 decades ago, the region embarked on the surveillance of sexually transmitted infections, which subsequently paved the way for broader participation in programs like the Gonococcal Antimicrobial Stewardship Programme and the establishment of the Regional System for Vaccines (SIREVA). The latter initiative, under the Pan-American Health Organization's leadership, aimed to monitor the antibiotic susceptibility of key bacterial strains for vaccine development. This legacy of vigilance was further cemented by the Latin American Antimicrobial Resistance Surveillance Network

Wound Masterclass - Vol 3 - March 2024

(ReLAVRA) in response to a cholera outbreak in 1996. It has been instrumental in supporting national reference laboratories and compiling data on AMR. Additionally, most countries in the region have contributed to the Global Antimicrobial Resistance and Use Surveillance System since 2015, showcasing their commitment to international collaboration.

Stalwarts of AMR Surveillance: USA and Canada The United States has assumed a proactive role in AMR surveillance with the establishment of the National Antimicrobial Resistance Monitoring System in 1996. This program, a collaborative effort among public health departments, universities, federal agencies, and more, reflects a concerted approach to address the crisis. Furthermore, the last decade has witnessed the release of 2 national action plans for combating AMR, the formation of a Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, and the launch of the CDC’s AMR Challenge to galvanize global organizations. Canada, too, has navigated

STOCK IMAGE

© Copyright. Wound Masterclass. 2024

Advancing Regional Efforts Against Antimicrobial Resistance in the Americas: The Imperative for Collaborative Action

“The study employed a methodological framework that extends prior research, enabling a granular examination of AMR's burden.”

STOCK IMAGE

contours in the Americas. This study's overarching objective is to comprehend AMR's ramifications on health in the region through meticulous data analysis, yielding both regional and country-specific insights. The study employed a methodological framework that extends prior research, enabling a granular examination of AMR's burden. Notably, the comprehensive approach encompassed empirical data, statistical modeling, and rigorous estimation techniques, underscoring the methodological rigor that informs its findings.

Quantifying the Toll of AMR the intricate landscape of AMR with the issuance of a comprehensive policy document in 2017, outlining a Pan-Canadian Framework for Action. This framework underscores the significance of collaborative action in curbing AMR's tide.

An Emerging Nexus: Integrating Surveillance Efforts Intriguingly, the historical underpinnings of AMR surveillance in the Americas have predominantly manifested as independent endeavors. Only in recent times have the tendrils of microbial surveillance, resistance analysis, and clinical insights begun to intertwine. However, this integration remains a nascent development. The dearth of studies presenting a holistic analysis, incorporating routine microbial surveillance, resistance patterns, and clinical outcomes, has impeded a comprehensive understanding of AMR's impact. This paucity hinders efforts to elucidate health losses attributed to AMR, the constraints of available data, and effective strategies to address this multifaceted quandary.

The Path Forward: Bridging Knowledge Gaps To bridge this gap, a pivotal study has emerged, illuminating the AMR landscape's

© Copyright. Wound Masterclass. 2024

The study's findings are sobering. In 2019, bacterial infections exacted a significant toll, resulting in an estimated 920,000 deaths and 23,347,000 disability-adjusted life years (DALYs) in the WHO Region of the Americas.

Alarmingly, over 40% of all infection-related deaths were linked to AMR. The spectrum of infectious syndromes implicated in this crisis includes bacterial lower respiratory infections, bloodstream infections, intra-abdominal infections, and urinary tract infections. These diseases collectively accounted for a substantial proportion of bacterial deaths associated with AMR.

Conclusion and Future Prospects As the study highlights the daunting burden of AMR in the Americas, its implications reverberate across global health agendas.

The message is clear: AMR is not just a concern for local health systems but demands a collaborative, cross-border response.

Comprehensive surveillance, evidencedriven policymaking, and multidisciplinary engagement are crucial components of this response. The study's insights serve as a clarion call for concerted action, emphasizing the need to align surveillance efforts, facilitate knowledge exchange, and foster collective strategies that transcend regional boundaries.

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds Editorial Summary This systematic review and economic evaluation assesses the health economics of a novel Bioactive Glass Wound Matrix (BGWM) in the management of chronic wounds. The primary objective is to evaluate the cost-effectiveness of BGWM compared to other treatment modalities, such as the standard of care (SOC), and identify areas where BGWM improves healthcare resource utilization and economic outcomes. The analysis included data from a randomized controlled trial on diabetic foot ulcers (DFUs) comparing BGWM to SOC, as well as multiple case series examining refractory wounds from various etiologies, including venous leg ulcers, pyoderma gangrenosum, radiation therapy, and chronic surgical wounds. The total cost of care associated with BGWM was compared to the costs of SOC and other therapies. The investigation revealed several statistically significant economic improvements, including reduced total cost of care across multiple study cohorts, decreased patient visit times, and lower secondary dressing costs.

Introduction

C Dr Steven Jung Chief Technology Officer, Engineered Tissue Solutions Rolla MO, United States

Dr Donald W. Buck II Plastic Surgeon, Specialist in Aesthetic and Reconstructive Surgery of the Face, Breast, Bbody, and Lipedema St Louis MO, United States

4

hronic, non-healing wounds represent a major health burden and contribute substantial costs to healthcare systems.

It is estimated that 2% of populations will develop a chronic wound during their lifetime, with 6.5 million Americans affected and costs in the billions per year in the United States alone.1 As such, wound care remains an area of high unmet need with opportunities for improved products and treatment approaches.

Advanced wound care strategies have explored the use of biologic products, including extracellular matrices derived from animal and human sources, as well as synthetically manufactured alternatives.2-4 However, many of these products are limited by the incorporation of unmatched allogeneic cells or harsh processing methods necessary for decellularization and pathogen inactivation, which can detrimentally impact the structural integrity and biological activity of the graft material.2 Clinical studies evaluating the efficacy of tissue-based products such as human amnion and chorion allografts, porcine urinary bladder matrices, porcine purified reconstituted bilayer matrices, fetal bovine collagen, and collagen hydrogels in the management of wounds have yielded variable outcomes.3,4 Time to apply product and storage conditions should also be considered. A common challenge across many of these trials is the lack of a well-defined, clinically relevant comparator group. For the subset of wounds refractory to conventional standard of care, bioactive glass wound matrices have emerged as a promising advanced wound care modality.5-9

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Early evidence indicates these bioactive matrices may improve healing rates and reduce time to wound closure compared to standard dressings.5-8 Novel bioactive glass wound matrix (BGWM) (Mirragen®, Engineered Tissue Solutions) has been successfully utilized in a variety of clinical situations where other advanced wound care products have failed to achieve desired outcomes.5-9 Unlike certain other biologic products, bioactive glass matrices do not contain allogeneic cellular components and avoid harsh processing methods, potentially offering a more consistent and effective solution for recalcitrant wounds.8 As reimbursement and adoption of new wound care products depends heavily on demonstrated economic value10-12, Health Economics Outcomes Research (HEOR) provides a crucial framework for evaluating the clinical and economic outcomes of BGWM.13

Overview of HEOR in Wound Care Costs of Standard of Care In the United States, the conservative annual cost of wound care is $28 billion, with the majority of these costs occurring in the outpatient setting.1 The average cost of treating a venous leg ulcer is estimated to be $4,000 to $5,000 per month.10 The mean cost per patient for diabetic foot ulcer treatment ranges from $10,000 to $20,000.11

Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“Comprehensive HEOR studies are vital to guide evidence-based decision making and ensure equitable access to advanced wound care modalities that meaningfully improve patient outcomes while providing economic value to the healthcare system.”

The average cost of treating a single fullthickness pressure ulcer is estimated to be $70,000.12 Approximately 15% of Medicare beneficiaries require treatment for at least one type of chronic wound or infection.1 These costs and statistics highlight the need for advanced wound care strategies to improve patient outcomes and reduce healthcare costs.

Factors Affecting Costs of Standard of Care 1.

2.

3.

4.

Rates and speed of wound closure Reductions in adverse events Impact on quality of life Both direct and indirect costs across the continuum of care

Comparative effectiveness studies incorporating appropriate Standard Of Care (SOC) controls are necessary to quantify the incremental clinical and economic benefits of BGWM. Wound care Health Economics and Outcomes Research (HEOR) must also consider the specific patient populations and care settings most likely to benefit from advanced matrix products.

Factors that may significantly outcomes and costs include: 1.

2.

3.

4.

5.

Wound etiology Size Duration Comorbidities Provider experience

influence

Ultimately, the success of innovative wound care products like bioactive glass matrices will depend on: • •

Demonstrating superior clinical outcomes Reasonable cost-effectiveness compared to current standards of care

Comprehensive HEOR studies are vital to guide evidence-based decision making and ensure equitable access to advanced wound care modalities that meaningfully improve patient outcomes while providing economic value to the healthcare system.

What Do We Know about Bioactive Glass Matrix So Far? Evidence Overview Methods A number of data sources were considered to provide a comprehensive economic analysis of BGWM. Table 1: Summary of the Referenced Clinical Work.

Study

Study Type

Wound Type(s)

Number of Wounds

Citation

1

RCT

DFU

40

8

2

Case Series

VLU

6

6

3

Case Series

PG

8

7

4

Case Series

Refractory Wounds

3

5

5

Case Series

3 DFU, 1 PU

4

13

6

Case Series

3 DFU, 1VLU

4

14

7

Time Study

Mixed

20

Present Work

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“The studies reviewed implemented a borate- based bioactive glass wound matrix BGWM for a range of chronic wound types, tailoring specific treatment protocols to individual patient groups. This approach ensured consistent application and monitoring, optimizing therapeutic outcomes across diverse clinical scenarios.”

Study 1: BGWM 40 patient Randomized Controlled Trial (RCT): A 40 patient RCT comparing the clinical and economic outcomes of BGWM versus SOC in Wagner 1 DFUs.8

Economic Outcomes

Study 2: Case Series of six Chronic Venous Leg Ulcers (VLUs) treated with BGWM.6

1.

Study 3: Case Series of eight Pyoderma Gangrenosum (PG) treated with BGWM.7

The following types of economic outcomes were evaluated:

2.

3.

4.

Study 4: Case series of three refractory wounds treated including longstanding surgical and radiation wounds treated with BGWM.5 Study 5: Case series of four chronic wounds with mixed etiologies including a pressure wound on the elbow and three DFUs treated with BGWM.13 Study 6: Health Economics Study: A study comparing the historical patient wound management costs with those after the implementation of BGWM in four DFUs.14 Study 7: Time study: A 20 patient study comparing the average patient visit time and potential for increased patient capacity and reimbursement when using BGWM versus SOC in a hospital outpatient department (HOPD) setting.

Existing published data cost estimates: Published studies reporting the average costs of treating venous leg ulcers, diabetic foot ulcers, and pressure ulcers and Standard-of-Care.10-12

5.

Total cost of care (TCOC) per healed patient Average treatment cost per patient Dressing costs and frequency of dressing changes Patient visit time and potential for increased patient capacity and reimbursement Comparison of costs to published data for treating different types of chronic wounds

Statistical Analysis Statistical significance was assessed using twotailed t-tests for continuous variables, with a p-value < 0.05 considered significant.

Study Analysis Design and Compliance The studies reviewed implemented a boratebased bioactive glass wound matrix BGWM for a range of chronic wound types, tailoring specific treatment protocols to individual patient groups.

This approach ensured consistent application and monitoring, optimizing therapeutic outcomes across diverse clinical scenarios.

An economic model was designed to evaluate the total cost of care (TCOC) over a 40-week period. This model took into account various cost inputs including the prices of products, fees for nursing and physician visits, costs associated with offloading boots, and additional expenses for treating wounds that remained unhealed after 12 weeks.8 Recruitment and Randomization Phases Study 1 was an RCT with strict enrollment criteria which included Wagner 1 DFU wounds of a certain size range, wounds that had existed

6

Wound Masterclass - Vol 3 - March 2024

Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“For each study, wounds were cleansed with sterile normal saline solution and debrided once prior to initial BGWM application. BGWM was shaped to fit the size of the wound bed and pressed directly in contact with the wound, covering the entire wound area. A cover dressing was applied over BGWM to fixate the matrix to the wound surface, and a secondary dressing was then applied to assit with exudate management.”

for a minimum number of weeks in a chronic state, and a variety of other factors including exclusion of smokers or those with infections.

During the run-in period, wounds that resolved more than 20% were excluded from the study.

Randomization was blinded between the SOC and BGWM groups.

Study 2 was a case series of chronic VLU wounds that had been present for an average of 15 weeks and in a non-healing state. Patients had previously received a vascular assessment and three of the five patients required venous ablation procedures to improve venous insufficiency.

Study 3 was a case series of eight refractory PG wounds from three patients ranging from months to years in age. Each wound had failed several previous treatment plans including SOC, and a variety of advanced skin substitute products.

Study 4 was a case series of three patients with refractory wounds from surgical procedures and radiation therapy. These wounds were selected due to there refractory state.

Study 5 was a case series of four chronic wounds including three DFUs and a pressure wound located on patient’s elbow. Each wound was selected for this case series due to multiple failed therapies including SOC, surgery, NPWT and advanced skin substitutes. .

treatment. Patients selected for this study had refractory wounds with at least one year in a wound care center prior to introduction of the BGWM. Study 7 was a study evaluating the patient visit times comparing SOC therapy vs. BGWM. A total of 20 patient visits, 10 consecutive visits to each therapy group, were timed in an HOPD setting to look at overall patient visit efficiency.

Treatment Phase For each study, wounds were cleansed with sterile normal saline solution and debrided once prior to initial BGWM application.

BGWM was shaped to fit the size of the wound bed and pressed directly in contact with the wound, covering the entire wound area. A cover dressing was applied over BGWM to fixate the matrix to the wound surface, and a secondary dressing was then applied to assit with exudate management. Where indicated clinically, a two-layer compression dressing, or off-loading device, was utilized and changed per the provider’s preferred protocols.5-8 The BGWM was reapplied approximately weekly, based on clinical assessment, without further debridement or product removal.

In Study 1 the treatment phase considered the comprehensive costs associated with nursing and physician care, the products used, and the treatments applied to unhealed wounds up to 40 weeks post-enrollment.8

Study 6 was a case series of three DFUs and one VLU that also assessed the cost differential from historical treatment before BGWM, and the patient costs incurred during BGWM

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“These findings suggest positive outcomes for using BGWM in treating chronic wounds, particularly DFUs, potentially improving healing rates and reducing healthcare costs.8 Total dressing costs with BGWM compared to SOC were also statistically less (p < 0.05).”

Study 6 meticulously recorded the costs associated with previous treatments and compared them to the costs incurred during BGWM therapy. The cost analysis included dressings and debridement but excluded skin grafts, cellular and tissue-based product costs, hospitalization, antibiotics, or pain medication costs.14 Validation of Healing Healing validation as implicitly based on clinical outcomes observed during treatment, with a focus on wound closure and wound closure rates.

group (37%, SD: 66). Moreover, individuals undergoing BGWM treatment had odds of healing that were over 11 times greater than those solely receiving SOC. Consequently, the finding that the difference in healing rates between treatment groups in this study (45%) is noteworthy. This finding is especially significant considering the effectiveness of bioactive glasses in similar populations and the severity of diabetic foot ulcer (DFU) wounds, as reported in various randomized controlled trials (RCTs) exploring different advanced wound care treatments.6 The BGWM demonstrated a 2.8x faster closure rate and a reduced time to heal compared to SOC (p < 0.001) which was statistically significant.

Study 1: Randomized Controlled Trial on Diabetic Foot Ulcers

These findings suggest positive outcomes for using BGWM in treating chronic wounds, particularly DFUs, potentially improving healing rates and reducing healthcare costs.8 Total dressing costs with BGWM compared to SOC were also statistically less (p < 0.05).

Results

2.

1.

No adverse events (AEs) related to infection of the index ulcer were reported in the BGWM group, while five such infections occurred in the SOC group.

Clinical Efficacy of Bioactive Glass Wound Matrix

Faster Healing Times and Reduced Costs

A randomized trial of 40 patients receiving SOC or BGWM for up to 12 weeks, the initial healing was assessed by complete epithelialization without drainage, with final healing evaluated by a panel of three blinded plastic surgeon wound experts. After 12 weeks, 70% of wounds in the BGWM group were healed compared to 25% in the SOC group, with the percent area reduction at 6 weeks (PAR) being significantly higher in the BGWM group (79%, SD: 48) compared to the SOC

3.

No Infections

Neuropathy Improvement

BGWM treatment led to a significant reduction in Semmes-Weinstein score compared to SOC alone (P = .008). In 40% of BGWM subjects a positive increase in sensation around the wound was noted.

4.

Healing times

The study’s findings underscore the efficacy of BGWM in facilitating wound healing compared to SOC. The data suggest that

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“In summary, while BGWM’s initial costs may appear higher than the SOC, its clinical effectiveness and resource efficiency results in a reduction in long- term care costs.

This analysis underscores the importance of considering both the direct costs and the clinical outcomes when assessing the economic impact of new medical treatments.”

BGWM not only enhances the rate of wound closure but also significantly reduces the healing time for patients. This is a critical factor in the management of DFUs, as prolonged wound openness increases the risk of infections and other complications, leading to a higher burden on patients and healthcare systems alike.

5.

Comparison to Published Costs of Standard of Care

Utilizing the RCT data, an established economic model was employed to evaluate the total cost of care (TCOC) during the study period for the Standard of Care (SOC) and BGWM. The TCOC provides a comprehensive look at the financial impact of each treatment method, incorporating all costs associated with patient care over the study period. For the SOC, the total cost of care for the study period was $102,864, which, when broken down to a per-patient basis, reveals a cost of $5,143. This figure encapsulates the aggregate of both healed and unhealed patient costs divided by the total number of patients. In contrast, BGWM total cost of care was higher, at $138,502 for the study period, with an individual patient cost averaging $6,925. Although there is a higher initial cost compared to SOC, long term costs are lower. 8 Delving deeper into the cost-effectiveness of the treatments, the TCOC was analyzed for patients who healed during the study.

The cost for a healed patient under SOC was $20,572. BGWM, however, presented a more favorable outcome, with the cost for a healed patient being substantially lower at $9,233.

This notable difference indicates that while BGWM’s upfront costs may seem higher, the treatment is more cost-effective in the long run, particularly when it leads to successful healing.

Importantly, the BGWM Total Cost of Care (TCOC) per healed patient (US$ 9,233) is lower than the previously published costs for treating diabetic foot ulcers ($10,000 to $20,000).8

A critical aspect to consider with HEOR in wound care is the cost associated when wounds do not heal. When evaluating the cost of unhealed wounds in the RCT, the unhealed wounds in the SOC cohort cost of $88,169, which is greater than the BGWM cost of unhealed wounds in this series ($63,924). This difference is pivotal in the overall cost savings achieved with BGWM, which were highlighted as significantly lower TCOC (p=0.001) and an average savings of $8,377 per patient over the period.

In summary, while BGWM’s initial costs may appear higher than the SOC, its clinical effectiveness and resource efficiency results in a reduction in long- term care costs. This analysis underscores the importance of considering both the direct costs and the clinical outcomes when assessing the economic impact of new medical treatments.

Study 2: Patient Case Series on Venus Leg Ulcers Study 2 focuses on venous leg ulcers in geriatric patients, featuring five patients with an average age of 80.3 years (ranging from 68 to 87), representing an elderly cohort with significant comorbidities affecting wound healing.

1.

Ulcer Size and Severity

The mean initial ulcer size was 13.5 cm2, indicating that many wounds were large.

BGWM facilitated healing even for the largest ulcer (56 cm2), suggesting effectiveness across a range of sizes and severity.6 An example of a VLU from this case series before and after treatment with BGWM in shown in Figure 1.

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“The ease of BGWM application and ability to use until full closure without frequent dressing changes, alongside the lack of need for systemic antibiotic therapy from the real world data trials, supports clinical efficacy.”

2.

Healing Time

A median healing time of 10 weeks compares favorably to expected healing times with standard of care.6

Study 3: Patient Case Series on Pyoderma Gangerosum 1.

Patient Profile

Significant pain reduction was reported by patients within just 2-3 dressing changes, from a mean of 5.8/10 to 0/10. An improved patient quality of life and treatment compliance was also noted.

Study 3 covers three patients with a total of eight PG ulcers, which were complex and challenging wounds associated with an inflammatory skin disease.5 Each of these patients failed to respond from conventional therapies over an extended period of time. An example of one of the PG wounds before and during the healing progression with BGWM is shown in Figure 2.

4.

2.

3.

Pain Reduction

Clinical Workflow

The ease of BGWM application and ability to use until full closure without frequent dressing changes, alongside the lack of need for systemic antibiotic therapy from the real world data trials, supports clinical efficacy.

Healing Time

The application of BGWM in this study resulted in healing trajectories for all previously non-healing wounds in patients with pyoderma gangerosum ulcers. The absence of systemic antibiotics during the continuum of care was noted.7

Figure 1: Example of a VLU treated with Bioactive Glass Wound Matrix (BGWM).

3.

Figure 1a: Patient with large, non healing medial leg wound, resistant to other treatment modalities.

All patients reported significant reductions in the pain levels associated with the PG ulcers.

1a

Figure 1b: Patient showing anterior view of nearly healed medial leg wound after BGWM.

1b

4.

Pain Reduction

Adverse Events

No adverse events were reported during the BGWM therapy.

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Figure 2: Healing Progression of a PG wound treated with Bioactive Glass Wound Matrix (BGWM).

Figure 2a: This patient had refractory Pyoderma Gangrenosum, which had not responded to treatment.

2a

Figure 2b: Post-application, day 1.

Wound shows signs of product integration.

Figure 2c: Post-application, 3 weeks.

The defect on close monitoring has decreased in size.

2c

2b

Study 4: Patient Case Series on Refractory Wounds 1.

Study 5: Patient Case Series Comparing Previous Treatment Costs to Costs Associated with BGWM 1.

Healing Time

On average, these wounds had remained open for 13.2 months before the intervention with BGWM. All wounds experienced healing within an average duration of 8.1 weeks following the application of BGWM. 3.

2d

Patient Profile

Study 4 explores treating three complex refractory wounds comprising two surgical and one radiation-induced wound in a patient group averaging 72 years of age (ranging from 56 to 84) with BGWM. The wounds resulted from varied medical interventions and conditions, indicating a mature demographic facing severe healing challenges.5 These wounds were notably challenging, having not responded to numerous advanced and expensive treatments and surgeries previously.

2.

Figure 2d: Post-application, 4 weeks.

The wound has fully healed.

BGWM Therapy

Results in these cases included full wound closure, rapid pain relief, avoidance of systemic antibiotics, and streamlined dressing changes.5

Patient Profiles

Patient 1 presented with a chronic left elbow wound following two operative incision and drainage procedures for an infected olecranon bursa with osteomyelitis and exposed bone.

The wound had persisted for 212 days prior to initiating BGWM treatment. Due to the chronicity and severity of the wound, the patient had significant tissue loss and bone exposure. Additionally, the patient had multiple comorbidities, including poorly controlled diabetes, chronic hemodialysis dependence, a pacemaker, upper extremity arterio-venous graft, multiple sclerosis, and a seizure disorder.

Patient 2 had a chronic left diabetic foot ulcer that had persisted for 420 days prior to BGWM treatment initiation. The patient presented with poorly controlled diabetes and peripheral vascular disease, contributing to the chronicity and severity of the wound. Previous treatments included two failed operations for surgical closure, as well as prior use of Integra and MicroMatrix. The wound exhibited significant tissue loss and necrotic debris.

Patient 3 presented with a chronic diabetic ulcer on her left leg that had been present for 540 days prior to initiation of BGWM therapy.

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“During the course of treatment with the BGWM, no adverse events were reported in any of the four patients. None of the patients in the case series experienced ulcer recurrence during the follow-up period after complete wound closure.”

The wound was complicated by bone exposure and osteomyelitis, and the patient had a history of a prior below-the-knee amputation of her right leg due to peripheral vascular disease.

Previous treatments included prolonged use of various wound care products, negativepressure wound therapy, hyperbaric oxygen, and multiple courses of antibiotics. The wound exhibited extensive tissue loss, necrotic debris, and signs of infection.

Patient 4 had a chronic foot wound following a left-sided transmetatarsal amputation. The wound had persisted for longer than 6 months and was complicated by osteomyelitis. The patient had poorly controlled diabetes and peripheral vascular disease. Previous treatments included multiple failed operations for surgical closure, as well as prior use of advanced modalities. The wound exhibited tissue loss, exposed bone, and signs of infection.13 2.

Wound Closure and Area Reduction Rates

Following initiation of BGWM treatment, Patient 1’s wound achieved complete closure 56 days after the first application of BGWM. The wound closure process was monitored closely during outpatient follow-up visits, with reapplication of the BGWM matrix as needed based on wound appearance and healing progress. Throughout the treatment period, the wound demonstrated a consistent reduction in size, eventually leading to full closure. The area reduction rate was calculated as [initial wound area - final wound area] / initial wound area * 100%.

Patient 2 healed completely 42 days after the initial application of BGWM. The wound closure process was rapid, indicating a positive response to BGWM treatment. Throughout the treatment period, the wound exhibited progressive reduction in size, with a notable decrease in wound area observed during follow-up visits.

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Patient 3, the chronic diabetic ulcer on the left leg achieved complete closure 66 days after initiation of BGWM treatment. Despite the complexity of the wound, including bone exposure and osteomyelitis, BGWM therapy facilitated significant wound healing progress.

Throughout the treatment course, the wound area decreased steadily, indicating ongoing tissue regeneration and closure. The area reduction rate was calculated to evaluate the rate of wound healing and assess the effectiveness of BGWM in facilitating tissue regeneration.

Patient 4’s chronic foot wound healed completely 56 days after the initiation of BGWM treatment. Despite the presence of osteomyelitis and tissue loss, BGWM therapy led to substantial wound closure within a relatively short time-frame. Throughout the treatment period, the wound area decreased progressively, reflecting ongoing tissue regeneration and wound healing. The area reduction rate was calculated to monitor the rate of wound closure and evaluate the efficacy of BGWM in facilitating tissue repair.

3.

Adverse Events and Ulcer Recurrence

During the course of treatment with the BGWM, no adverse events were reported in any of the four patients. None of the patients in the case series experienced ulcer recurrence during the follow-up period after complete wound closure.13 4.

Economic Impact

Prior to initiating the BGWM treatment, the average estimated cost of prior wound interventions was approximately $87,750 per patient. However, with the application of BGWM treatment, the

Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“When comparing the estimated costs of prior treatments to the cost of closure using BGWM, a hypothetical reduction in treatment costs of $84,186 per patient was observed compared to SOC (p < 0.001).13 Additionally, the average reduction in wound duration was approximately 336 days per patient.”

average cost of wound closure reduced significantly to $3,564 per patient.13 Furthermore, when comparing the estimated costs of prior treatments to the cost of closure using BGWM, a hypothetical reduction in treatment costs of $84,186 per patient was observed compared to SOC (p < 0.001).13 Additionally, the average reduction in wound duration was approximately 336 days per patient.

Study 6: Patient Case Series Reducing Treatment Costs in Hard-To-Heal Wounds with BGWM 1.

Patient 3 was a 39 year-old female with a 1 year old (~365 days) recalcitrant VLU which had been refractory to other advanced modalities.

2.

Healing Progression

Patient 1 saw her first ulcer healed after 9 applications of BGWM over a period of 15 weeks. The second ulcer healed following 13 applications of BGWM over 20 weeks. Patient 2 saw his ulcer respond positively to the BGWM treatment, closing after 7 applications within a seven-week timeframe. Patient 3 saw their wound close after four applications over an 11 week time period.14

Patient Profiles 3.

Patient 1 was a 60-year-old female who presented with two DFUs that she had endured for eight years (~2900 days). A progression of the healing from before BGWM treatment through complete closure is shown in Figure 3.

Patient 2 was a 68-year-old male who had a DFU that had been present for 1.5 years (~550 days).

Economic Impact

Patient 1 TCOC with BGWM therapy (total for both wounds) was $18,113, an 80% decrease from the $89,568 TCOC prior to BGWM. Patient 2 TCOC with BGWM therapy was $9,506, a 50% decrease from the $19,080 TCOC prior to BGWM. Patient 3 TCOC with BGWM therapy was $5,432, a 50% decrease from the $10,816 TCOC prior to BGWM.14

Figure 3: 60-year-old female with two DFUs on the plantar aspect of her left foot, present for 8 years. Progress before, after and during BGWM shown.

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

“The time study revealed that BGWM could save 19 minutes per patient visit (26 minutes vs. 45 minutes)."

Study 7: Time Savings and Increased Patient Capacity The time study revealed that BGWM could save 19 minutes per patient visit (26 minutes vs. 45 minutes) compared to SOC (p < 0.001) at HOPD Wound Clinic. Extrapolating this time savings over the course of an outpatient clinic day, this could equate to an extra 8 patients to be treated per room per day, (18.4 patients with BGWM vs. 10.6 patients). In a busy clinic with 3-6 rooms, the potential additional reimbursement, if a skin substitute is applied, could range from $42,000 to $84,000 per day.

In a real-world scenario, where approximately 10-15% of wounds use skin substitutes, the potential additional reimbursement related to increased office throughput and patient volume could result in $4,200 to $8,400 per day. These findings suggest that using BGWM in HOPD settings could result in increased reimbursement and cost savings, improved outcomes, presenting a positive economic story for the product.

14

Studies 2-6: The strengths in these case studies are that the cases are real-world complex and refractory wounds of multiple etiologies including PG. While there was no control arm in these studies, all of these wounds previously failed a combination of SOC and or advanced wound therapies including skin substitutes and skin grafts. The weaknesses to these case series include that fact that they include are relatively small numbers of wounds and no control group.

The investigators were not blinded to the therapy which could introduce bias and there was no randomization to a comparator group.

Promising pilot results that support further investigation in larger controlled trials.

Study 7: The strength of this study is that it recorded data from 10 consecutive patient visits of both the BGWM and SOC. The randomness of the patient variables such as patient mobility, wound location, and normal daily occurrences in an HOPD were consistent for both groups.

The investigators were not blinded to the therapy, so this could have introduced bias.

Strengths and Weaknesses of the Studies

Conclusions

Study 1: The strengths lie in its robust trial design, ensuring reliability in the findings, supported by adequate statistical power.

Additionally, the standardized approach to standard of care (SOC) and adherence to CONSORT guidelines for reporting enhance the study’s credibility. However, weaknesses include the absence of investigator blinding, which could introduce bias. The trial’s results indicate a significant enhancement in wound healing for Wagner 1 diabetic foot ulcers (DFUs) upon the addition of BGWM to standard of care. This improvement bears positive implications for both infection prevention and neuropathy management. Nonetheless, further investigations are suggested to support these findings further, particularly in more complex wound scenarios where the efficacy of BGWM might vary.

Chronic, non-healing wounds are a substantial financial burden, and treatments that can reduce this burden while promoting healing represent a significant advancement in wound care. The utilization of BGWM therapy in the treatment of chronic and refractory wounds is a significant advancement in the field of wound care. These therapies, grounded in the physiologic properties of BGWM at the wound

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Enhancing the Health Economics of Wound Care: A Review of Economic Impact Studies Utilizing Bioactive Glass Wound Matrix in Chronic Wounds

interface, have demonstrated the capacity to accelerate healing while concurrently minimizing the costs associated with patient care such as reducing average visit times, reducing the average treatment costs per patient, and improving patient outcomes. In addition, the resource efficiencies associated with BGWM usage could allow for higher daily patient volumes, which would allow more patients to be treated.

The significant difference in TCOC between BGWM and SOC, particularly for healed patients, is noteworthy. The BGWM model of care, requiring fewer applications and less intensive nursing visits, not only aligns with the clinical benefits of accelerated healing but also with economic efficiencies. These findings are crucial for payers, providers, and patients, demonstrating that the BGWM upfront costs are offset by its overall cost-effectiveness, particularly in a healthcare environment increasingly focused on value-based care.

Declarations Dr Donald W. Buck II; Director of Plastic Surgery Mercy South (St. Louis, MO), Plastic Surgeon, Specialist in Aesthetic and Reconstructive Surgery of the Face, Breast, Body, and Lipedema, Chief Medical Officer of ETS LLC Dr Steven B. Jung PhD; Inventor of BGWM Technology and Chief Technology Officer of ETS LLC

Leveraging state-of-the-art technologies like BGWMs represents a powerful strategy to facilitate wound closure and reduce morbidity.

While further work remains to establish definitive evidence-based guidelines, BGWMs are emerging as an exciting solution to reframe the paradigm of chronic and refractory wound care for the 21st century.

References 1. Nussbaum, S. R., Carter, M. J., Fife, C. E., DaVanzo, J., Haught, R., Nusgart, M., & Cartwright, D. (2018). An economic evaluation of the impact, cost, and medicare policy implications of chronic nonhealing wounds. Value in Health, 21(1), 27-32. https://doi.org/10.1016/j. jval.2017.07.007 2. Chattha, A., Naeger, T., Whyte, W., Bonias, P., Huddleston, E., Wu, L. C., & Eberlin, C. T. (2020). Decellularized human placenta-derived extracellular matrix: an update on its use in regenerative medicine. International Wound Journal, 17(3), 600-610. https://doi.org/10.1111/iwj.13322 3. Vowden, P., & Vowden, K. (2017). Wound dressings: principles and practice.

Surgery, 35(9), 489-494. https://doi. org/10.1016/j.mpsur.2017.06.005 4. Cazzell, S. M. (2017). Challenging Clinical Scenarios: Evaluating the Safety and Efficacy of Available Biologic Products for Venous Leg Ulcers. International Wound Journal, 14(S3), 23-31. https://doi.org/10.1111/ iwj.12767 5. Castillo-Garcia E, Thuy Nguyen P. Complex Refractory Wounds: How to Overcome Treatment Recalcitrance and Restore the Healing Trajectory Using Innovative Bioactive Glass. Wound Masterclass. Volume 3. March 2024.

6 Johnson ML, Armstrong DG, Ortega W. How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers in Geriatric Patients with Multiple Comorbidities? Wound Masterclass. Volume 3. March 2024.

7 Laurentin LA, Buck DW, Rivera D. Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing for Patients with Pyoderma Gangerosum Ulcers? Wound Masterclass. Volume 3. March 2024.

8 Armstrong DG, Orgill DP, Galiano RD, et al. A multi- centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. Int Wound J. 2021;1-11. doi:10.1111/iwj.13675

9. Jung S, Schultz G, Mafiz AI, Bevels E, Jaskula K, Brownell K, Lantz E, Strickland A. Antimicrobial effects of a borate-based bioactive glass wound matrix on wound- relevant pathogens. J Wound Care. 2023 Dec 7;32(12):763. https://doi.org/10.12968/jowc.2023.32.12.763 10. Ma, H., O’Donnell, T. F., Jr, Rosen, N. A., & Iafrati, M. D. (2014). The real cost of treating venous ulcers in a contemporary vascular practice. Journal of Vascular Surgery: Venous and Lymphatic Disorders, 2(4), 355-361. https://doi. org/10.1016/j.jvsv.2014.04.006 11. Mutluoglu, M., Sivrioglu, A. K., Eroglu, M., Uzun, G., Turhan, V., Ay, H., & Lipsky, B. A. (2013). The implications of the presence of osteomyelitis on outcomes of infected diabetic foot wounds. Scandinavian Journal of Infectious Diseases, 45(7), 497-503. https://doi.org/10.3109/00365548.2013.765589) 12. Brem, H., Maggi, J., Nierman, D., Rolnitzky, L., Bell, D., Rennert, R., Golinko, M., Yan, A., Lyder, C., & Vladeck, B. (2010). High cost of stage IV pressure ulcers. American Journal of Surgery, 200(4), 473-477. https://doi. org/10.1016/j. amjsurg.2009.12.021) 13. Buck, D.W., II, MD, FACS. Innovative Bioactive Glass Fiber Technology Accelerates Wound Healing and Minimizes Costs: A Case Series. Adv Skin Wound Care. 2020;33(3):1-6.

14. Rathinasamy P, Beckford J.C., How to Reduce Treatment Costs for Hard-toHeal Wounds: The Bioactive Glass Wound Matrix. Wound Masterclass. Volume 3.March 2024 15. Jung S., Day T., Boone T., Buziak B., Amin O., (2019). Anti-biofilm Activity of Two Novel, Borate Based, Bioactive Glass Wound Dressings. Biomedical Glasses, 5(1) 67-75. https://doi.org/10.1515/bglass-2019-0006

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Bioactive glass: Clinically Shown to Support Wound Closure

1

79.4% vs. 36.5%

In a randomized controlled trial, Mirragen doubled the wound area reduction as 12 weeks (79.4% vs. 36.5%) as compared to the standard of care (collagen alginate dressing).

1

2.8x

Mirragen increased healing rate 2.8x vs. SOC in the 12 week trial.

1

To learn more please visit our website at www.ets123.com.

0 infections

SOC had 5 patients withdrew due to infection; Mirragen had 0 infections during the 12 week trial.

1.Armstrong DG,Orgill DP, Galiano RD, et al. A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. Int Wound J. 2021;1-11. doi:10.1111/iwj.13675. This study was funded by a research grant from ETS to the Professional Education and Research Institution

©2024 ETS Wound Care, LLC. Mirragen is a registered trademark of ETS Wound Care, LLC. All rights reserved

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How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Limb Threatening Ischaemia?

Editorial Summary Chronic limb-threatening ischaemia, marked by severely reduced blood flow, poses a major wound healing challenge and threat of amputation.1-3 Emerging biotechnology however brings new promise through biodegradable matrices. These innovative extracellular matrix products aim to stimulate angiogenesis and revascularization in limbs previously deemed unsalvageable.4 Findings suggest biodegradable temporising matrices (BTM), properly integrated with standard of care, can achieve significant wound closure and limb salvage.

Introduction

F

or wound specialists, chronic limb ischaemia is among our most recalcitrant diagnoses - often resistant even to goldstandard revascularization techniques. These limb-threatening conditions result from severe arterial blockages depriving tissues of sufficient perfusion for cell viability and healing. Critical limb ischaemia (CLI), also known as chronic limb-threatening ischaemia (CLTI), represents the most advanced state of peripheral arterial disease (PAD) and manifests as rest pain, nonhealing ulcers, and/or gangrene. Ulceration, infection, and necrosis abound as oxygen saturations plunge perilously below the 3050mmHg required for remodeling. More than 10% of patients with PAD may develop CLTI, and 55% of patients hospitalised with CLTI are readmitted within one year. It is vital that these patients are identified early in our clinical practice. 1-4

It is reported 10% of PAD patients may progress to develop CLTI, the most severe form of PAD. PAD itself is very common, affecting over 200 million people worldwide, so this translates to a large number of patients at risk for CLI. 2

Readmission Rates The one-year readmission rate for patients hospitalized with CLTI is 55%, which indicates the chronic and complex nature of this condition. Readmissions are often due to recurrent pain, non-healing wounds, infections, or other complications.3

Importance of Early Identification: Identifying PAD patients who are progressing toward CLTI is crucial for preventing amputations, disability, and death. Earlier diagnosis allows for more aggressive risk factor modification (e.g. smoking cessation, glycaemic control in diabetes) and treatment (e.g. revascularization procedures).

Table 1: Features of Critical Limb Ischaemia.

Ms Victoria Bristow Vascular Specialist Nurse, Cambridge University Hospitals

Rest pain Numbness Skin changes: shiny, smooth or dry skin Thickening of toenails Absent/diminished pulses legs/feet Non-healing ulcers Gangrene

Cambridge, United Kingdom

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All clinicians should assess for PAD signs/ symptoms like claudication, non-healing ulcers, absent pulses, and incorporate tools like the ankle-brachial index, or the use of toe pressures.

In summary, CLTI has a high prevalence and identifying these high-risk patients early is essential for improving outcomes and reducing the very high rates of readmission and complications. Increasing awareness of CLI among clinicians across specialties who care for patients with vascular disease is an important priority. 1-3

How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Ischaemia?

“Achieving adequate wound coverage and promoting healing in complex wounds remains a significant challenge in surgical practice. Biodegradable Temporising Matrix (BTM) is a synthetic dermal scaffold that has gained increasing attention in recent years due to its unique properties and potential benefits in wound management. Evidence has been well established to support studies on the applications and outcomes of BTM in various clinical settings, including burns, trauma, and chronic wounds."

The Reconstructive Challenge: What is the evidence for BTM? Achieving adequate wound coverage and promoting healing in complex wounds remains a significant challenge in surgical practice.

NovoSorb® Biodegradable Temporising Matrix (BTM) (PolyNovo Biomaterials Pty Ltd., Port Melbourne, VIC, Australia) is a synthetic dermal scaffold that has gained increasing attention in recent years by clinicians due to its unique properties and potential benefits in wound management. Evidence has been well established to support studies on the applications and outcomes of BTM in various clinical settings, including burns, trauma, and chronic wounds. 4-18 BTM is composed of a biodegradable polyurethane foam with a outer sealing membrane, designed to provide a temporary wound coverage while allowing for the development of a neodermis. 4,18

Mechanism of Action: BTM acts as a temporary dermal scaffold, providing a protective barrier and a supportive matrix for the ingrowth of host cells and neovascularization. The porous structure of the BTM allows for the migration of fibroblasts and endothelial cells, promoting the formation of a neodermis.15 As the wound heals, the BTM gradually biodegrades, leaving behind a wellvascularized bed suitable for skin grafting or secondary wound closure. 4,18

Applications in Burns: The use of BTM in the management of burn injuries has been extensively studied. In a retrospective case review by Greenwood et al., BTM was used in the reconstruction of fullthickness burns wounds. 15 The

authors

reported

successful

closure and favorable long-term outcomes, with minimal complications and good cosmetic results. BTM has been studied reasonably extensively in patients with burns, necrotising fasciitis and, more recently, in diabetic foot disease.

In a comparative study by Selig et al., BTM was compared to split-thickness skin grafting (STSG) in the treatment of deep partial and fullthickness burns.19 The authors found that BTM was associated with reduced pain, improved scar quality, and better patient satisfaction compared to STSG. These findings suggest that BTM may offer advantages over traditional burn management techniques in select patient populations. 19

Applications in Reconstructive Surgery: BTM has also been utilized in the management of and in reconstructive surgical procedures. In a retrospective review by Wagstaff et al., BTM was used in the reconstruction of free flap donor sites in a variety of surgical procedures, including head and neck reconstruction, breast reconstruction, and extremity reconstruction.

The authors found that BTM was associated with reduced donor site morbidity, improved healing times, and better cosmetic outcomes compared to traditional donor site management techniques. 17

Applications in Chronic Wounds: The use of BTM in the management of chronic wounds, such as diabetic foot ulcers and venous leg ulcers, has emerging evidence suggesting that BTM may offer benefits in this patient population.

wound

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How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Ischaemia?

“This dermal matrix can cover important structures to maintain structural function such as vessels, joint capsules, bone and tendons. This is important in vascular patients to enable them to continue to be mobile avoiding major limb amputation which could then lead to a longer hospital admission and for some, loss of independent living. The matrix is initially placed over the defect to create a neodermis.”

Review of Clinical Case BTM is a dermal matrix that is commonly used in extensive and hard to heal wounds. Dermal matrices can cover important structures to maintain structural function such as vessels, joint capsules, bone and tendons. These are important in vascular patients to enable them to continue to be mobile avoiding major limb amputation which could then lead to a longer hospital admission and for some, loss of independent living. The matrix is initially placed over the defect to create a neodermis.

A 62-year-old male presented to the emergency department (ED) with extensive tissue necrosis involving the dorsum of the foot, multiple toes, and the calf as shown in Figure 1. Consent was gained from the patient to share photos in this case review. Physical examination revealed a palpable femoral pulse on the right leg, with no distal pulses palpable. The patient and his daughter reported three prior missed diagnoses at a local district hospital. The patient was admitted to the vascular ward for further evaluation and management. Revascularization was achieved through iliac angioplasty and a femoral-to-femoral crossover graft using polytetrafluoroethylene (PTFE).

Given the extensive tissue loss, the team deliberated on the salvageability of the limb.

The patient was discharged home to allow for further demarcation, with regular follow up as an outpatient.

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Having recently attended a presentation on the use of Biodegradable Temporising Matrix (BTM) in burn patients, a consultant colleague and I proposed this novel approach. The patient was counseled on the innovative nature of this treatment and the potential for limb salvage, with the understanding that a belowknee amputation would be the alternative. The patient expressed a strong desire to attempt limb preservation. During outpatient follow-up, sharp debridement was performed, revealing the eschar's role in protecting vital structures such as tendons, bone, and blood vessels. The patient was scheduled for BTM application under general anesthesia in a sterile operating theatre setting.

Figure 1: Right Lower Leg showing extensive necrosis.

How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Ischaemia?

“The matrix was applied in the operating theatre under general anaesthesia in full sterile conditions. With the BTM the wound needs to be able to bleed in a controlled manner through the matrix to encourage angiogenesis and create a neodermis.”

The necrosis continued to demarcate as shown in Figure 2 and the patient underwent amputation of some toes. Intraoperatively, the BTM was applied to the dorsum of the foot and calf, allowing for controlled bleeding through the matrix to promote angiogenesis and neodermis formation as shown in Figure 3. The matrix was secured with staples, and negative pressure wound therapy (NPWT) was employed for protection and exudate management.

Weekly dressing changes were conducted for seven weeks, with wound photography and NPWT replacement on the forefoot and posterior calf. Visible wound contraction was noted. At week seven, the BTM was delaminated by removing the staples and peeling back the sealing membrane. Upon removal, some slough Figure 2: Overview of the necrosis demarcation.

tissue and islands of epithelialization were present. Simple dressings were then applied with silver as the primary dressing as per the instruction for use from the manufacturers.

This was carried out by district nurses until week 24 at which the wound had fully healed.

The patient continued to be monitored closely in the outpatient setting until fully healed.

This patient highlights the potential for BTM to facilitate limb salvage in CLTI patients with extensive tissue loss, alongside traditional revascularization methods. Careful patient selection, multidisciplinary collaboration, and close post-operative monitoring are essential for the successful implementation of this innovative approach.

Figure 4: Overview of healing progression.

Figure 3: Fixation of BTM with staples after wound debridement.

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How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Ischaemia?

“Conventional treatments, such as endovascular angioplasty and bypass surgery, often fail to adequately restore distal perfusion, necessitating innovative solutions to promote wound healing and prevent limb loss. Biodegradable temporising matrix (BTM) has emerged as a promising adjunct therapy for limb salvage in CLTI patients with extensive tissue loss."

Discussion CLTI, the most advanced stage of PAD, presents a significant challenge for wound care professionals. Characterized by the triad of rest pain, non-healing ulcers, and gangrene, CLTI results from severe arterial obstruction, leading to critically reduced tissue perfusion.

This clinical scenario also has an added higher risk of amputation and mortality, and high rehospitalization rates, .1-3 Conventional treatments, such as endovascular angioplasty and bypass surgery, often fail to adequately restore distal perfusion, necessitating innovative solutions to promote wound healing and prevent limb loss.

Biodegradable temporising matrix (BTM) has emerged as a promising adjunct therapy for limb salvage in CLTI patients with extensive tissue loss.4

Reconstructive Methods in CLTI The management of CLTI involves a multidisciplinary approach, with the primary goal of restoring adequate perfusion to the affected limb and promoting wound healing.

Revascularization techniques, such as endovascular angioplasty and bypass surgery, are the mainstay of treatment for CLTI. However, these interventions may not always be successful in restoring distal perfusion, particularly in patients with extensive tissue loss and poor distal runoff.17

Additional Include:

Reconstructive

Methods

Split-thickness skin grafting (STSG): STSG involves harvesting a thin layer of skin from a donor site and applying it to the wound bed.

While STSG can be effective in promoting

wound closure, it requires a well-vascularized wound bed and may result in donor site morbidity and suboptimal cosmetic outcomes.

Local flaps: Local flaps involve mobilizing adjacent tissue to cover the wound defect.

This technique can provide better cosmetic results and maintain sensation in the affected area. However, local flaps may not be feasible in patients with extensive tissue loss or compromised vascularity in the surrounding tissue. 16 Free flaps: Free flaps involve harvesting tissue from a distant site and transferring it to the wound defect using microvascular techniques.

This method can provide well-vascularized tissue coverage but requires specialized surgical expertise and may be associated with longer operative times and higher complication rates. 18 Dermal substitutes: Dermal substitutes, such as acellular dermal matrices (ADMs) and BTM, provide a temporary scaffold for neodermis formation and promote wound healing. These products can be used in combination with STSG or as standalone treatments, depending on the wound characteristics and patient factors. 1-18

BTM in CLTI Reconstruction Novosorb® BTM is a synthetic dermal scaffold designed to provide temporary wound coverage while facilitating the development of a neodermis.4 The porous structure of BTM allows for cellular migration and neovascularization, promoting the formation of a well-vascularized wound bed suitable for skin grafting or closure.4 Several studies have demonstrated the effectiveness of BTM in various clinical settings, including burns, trauma, and chronic wounds. 1-18 BTM may reduce the risk of amputation and improve patient outcomes in CLTI. 21

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How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Ischaemia?

“In the context of CLTI, BTM may offer several advantages over traditional reconstructive methods. Firstly, BTM can be applied directly to the wound bed, even in the presence of exposed tendons, bones, or hardware, providing a suitable environment for wound healing. Secondly, BTM does not require a separate flap donor site, reducing the risk of donor site morbidity and improving patient comfort.”

In the context of CLTI, BTM may offer several advantages over traditional reconstructive methods. Firstly, BTM can be applied directly to the wound bed, even in the presence of exposed tendons, or bones, providing a suitable environment for wound healing.4 Secondly, BTM does not require a separate free flap donor site, reducing the risk of donor site morbidity and improving patient comfort.4 Thirdly, BTM can be used in combination with other reconstructive methods, such as STSG, to improve wound healing outcomes and reduce the need for additional surgical interventions. 4 This patient presented demonstrates the successful application of BTM in a patient with CLTI and extensive tissue loss. Following revascularization and debridement, BTM was applied to the wound bed, allowing for bleeding through the matrix to encourage angiogenesis and neodermis formation. Negative pressure NPWT was used for protection and exudate control. After seven weeks, the graft was delaminated, revealing granulation tissue with islands of epithelialization. Complete wound healing was achieved at 24 weeks.

This case highlights the potential of BTM to aid wound healing in revascularized CLTI patients with extensive tissue loss, particularly when exposed tendons and bones are present by providing a suitable environment for wound healing and promoting neovascularization,

Challenges and Future Directions Despite the promising results of BTM in various clinical settings, its widespread adoption in managing CLTI wounds remains challenging.

Robust randomized controlled trials clarifying optimal patient selection, timing of application, and product choice are required . Furthermore, the integration of BTM into standard wound care protocols requires a multidisciplinary approach, with close collaboration between vascular surgeons, wound care specialists, and

other healthcare professionals.

BTM represents a promising solution for limb salvage in CLTI patients with extensive tissue loss, offering a viable option when conventional revascularization techniques have failed. By providing a temporary scaffold for neodermis formation and promoting neovascularization, BTM can aid in wound healing and may avoid amputation. The case presented highlights the potential to improve patient outcomes, reduce amputation rates, shorter hospital stays, and improve quality of life for patients.

As the field of regenerative medicine advances, BTM is very likely to play an increasingly important role in the management of complex wounds and the prevention of limb loss in CLTI patients. However, further research is needed to establish the optimal use of BTM in CLTI management and to address the challenges of integrating this innovative therapy into standard wound care protocols. By expanding our understanding of BTM and its role in CLTI reconstruction, we can improve patient outcomes and reduce the burden of this debilitating condition on patients and healthcare systems alike.

Innovations in regenerative medicine using biodegradable matrices to deliver progenitor cells/proteins restoring the microcirculation offer glimmers of new hope but meaningful real-world integration remains challenging.

Robust randomised controlled trials clarifying optimal patient selection, timing of application and product choice are sparse. Thoughtful, multidisciplinary consideration balancing matrix benefits/risks and health economics are sure to follow.

To conclude, we have found that BTM provides a useful adjunct to aid wound healing in revascularised CLTI patients with extensive tissue loss, especially when exposed tendons and bones are present.

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How Can A Biodegradable Matrix Offer Limb-Saving Options for Chronic Ischaemia?

“BTM provides a useful adjunct to aid wound healing in revascularised CLTI patients with extensive tissue loss, especially when exposed tendons and bones are present.”

References 1. Conte MS, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg. 2019 Jun;69(6S):3S-125S.e40. doi: 10.1016/j.jvs.2019.02.016. Erratum in: J Vasc Surg. 2019 Aug;70(2):662. PMID: 31159978.

2. Duff S, Mafilios MS, Bhounsule P, Hasegawa JT. The burden of critical limb ischemia: a review of recent literature. Vasc Health Risk Manag. 2019;15:187-208. doi: 10.2147/VHRM. S209241. PMID: 31417268.

3. Agarwal S, Sud K, Shishehbor MH. Nationwide trends of hospital admission and outcomes among critical limb ischemia patients: from 2003-2011. J Am Coll Cardiol. 2016;67(16):19011913. doi: 10.1016/j.jacc.2016.02.040. PMID: 27102506.

4. Lim P, Chong SJ, Goh J, Oon HH, Cheng A, Tay SC, Tan BK. Novosorb® Biodegradable Temporising Matrix (BTM) and its Applications. Surg Technol Int. 2023;42:27-36. PMID: 37053370.

5. Betar N, Li W, Gawaziuk JP, Logsetty S. Clinical outcomes and resource utilisation in patients with major burns treated with NovoSorb® BTM. Burns. 2023;49(4):961-969. PMID: 37344307.

6. Lo CH, Deleyiannis FWB, Dini M, Douglas HE, Biedermann T, Reichmann E, et al.

Long-term scarring outcomes and safety of patients treated with NovoSorb® Biodegradable Temporizing Matrix (BTM): An observational cohort study. JPRAS Open. 2023;35:224-233.

PMID: 37360978.

7. Schlottmann F, Held M, Medina D, Kerrigan CL. Treatment of Complex Wounds with NovoSorb® Biodegradable Temporising Matrix (BTM)-A Retrospective Analysis of Clinical Outcomes. J Pers Med. 2022;12(12):2020. PMID: 36556223.

8. Harvey NM, Farroha A, Womack D, Ead JK. Artificial dermal templates: A comparative study of NovoSorb™ Biodegradable Temporising Matrix (BTM) and Integra® Dermal Regeneration Template (DRT). Burns. 2022;48(6):1412-1419. PMID: 35462204.

9. Li H, Tan A, Lim P, Lee SSJ, Leow MQH, Chong SJ. Experience with NovoSorb® Biodegradable Temporising Matrix in reconstruction of complex wounds. ANZ J Surg. 2021;91(12):2651-2655.

PMID: 34085755 Free PMC article.

10. Farroha A, Frew Q, El-Muttardi N, Philp B, Dziewulski P. Treatment of Necrotizing Fasciitis with NovoSorb® Biodegradable Temporizing Matrix™ and RECELL® Autologous Skin Cell Suspension: A Case Series. Wounds. 2021;33(2):48-54. PMID: 33449542 11. Austin CL, Hanson SE, Travis TE. Treatment of Necrotizing Fasciitis with NovoSorb® Biodegradable Temporizing Matrix™ and RECELL® Autologous Skin Cell Suspension: A Case Series. J Burn Care Res. 2023;44(2):269-273. PMID: 38085950

12. Wu SS, Friedrich JB, Friedrich PF, Moran SL, Haddock NT. Upper Extremity Wounds Treated with Biodegradable Temporizing Matrix versus Collagen-Chondroitin Silicone Bilayer. J Hand Microsurg. 2022;14(3):175-180. PMID: 38152680 Free PMC article.

13. Knightly N, Jones S, Soni M. NovoSorb Biodegradeable Temporizing Matrix for Reconstruction of Multiplanar Degloving Injury of the Upper Limb. Plast Reconstr Surg Glob Open.

2023;11(5):e4851. PMID: 37020984 Free PMC article.

14. Greenwood JE, Dearman BL. Split skin graft application over an integrating, biodegradable temporizing polymer matrix: immediate and delayed. J Burn Care Res. 2012;33(1):7-19. PMID: 21941194 15. Greenwood JE, Schmitt BJ, Wagstaff MJD. Experience with a synthetic bilayer Biodegradable Temporising Matrix in significant burn injury. Burns Open. 2018;2(1):17-34. doi: 10.1016/j. burnso.2017.11.002.

16. Wagstaff MJD, Schmitt BJ, Caplash Y, Greenwood JE. Biodegradable Temporising Matrix (BTM) for the reconstruction of defects following serial debridement for necrotising fasciitis: A case series. Burns Open. 2019; 3:12-30.

17. Wagstaff MJD, Schmitt BJ, Coghlan P, Finkemeyer JP, Caplash Y, Greenwood JE. A biodegradable polyurethane dermal matrix in reconstruction of free flap donor sites: a pilot study. ePlasty 2015; 15:102-18.

18. Masterclass Guide: Synthetic Dermal Matrix: Novosorb Biodegradeable Temporising Matrix (BTM). Wound Masterclass. Volume 1. No 1. June 2022.

19. Selig HF, Lumenta DB, Giretzlehner M, Jeschke MG, Upton D, Kamolz LP. The properties of an "ideal" burn wound dressing--what do we need in daily clinical practice? Results of a worldwide online survey among burn care specialists. Burns. 2012;38(7):960-966. doi: 10.1016/j. burns.2012.04.007.

20. Kinlay S. Management of Critical Limb Ischemia. Circ Cardiovasc Interv. 2016 Feb;9(2):e001946. doi: 10.1161/CIRCINTERVENTIONS.115.001946.

21. Guerriero FP, Clark RA, Miller M, Delaney CL. Overcoming barriers to wound healing in a neuropathic and neuro ischaemic diabetic foot cohort using a novel bilayer biodegradable synthetic matrix. Biomedicines. 2023;11(3):721.https://doi.org/10.3390/biomedicines11030721 22. Kuang B, Pena G, Cowled P, Fitridge R, Greenwood J, Wagstaff M, Dawson J. Use of Biodegradable Temporising Matrix (BTM) in the reconstruction of diabetic foot wounds: A pilot study. Scars Burn Heal. 2022;8:20595131221122272. doi: 10.1177/20595131221122272

Supported by

polynovo.com

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Biodegradable Temporising Matrix

For the reconstruction of diabetic foot wounds and venous leg ulcers.

BTM supports cellular migration and formation of neodermis.1,2 • It provides a porous framework that bioabsorbs, leaving a robust vascularized dermal layer.3 • A temporary sealing membrane protects the wound while the body heals.4 Indicated for full or deep partial thickness burns, traumatic wounds, complex vascular and surgical and reconstructive wounds.

Infected Diabetic Foot Ulcer

Wound prior to debridement

Delamination of BTM after week 4.5

Follow up at 4 months post grafting

Discover more at: polynovo.com

Discover more: polynovo.com Refer to the Instructions For Use for full device details. References: 1. Greenwood JE, Schmitt BJ, Wagstaff MJD. Experience with a synthetic bilayer Biodegradable Temporising Matrix in significant burn injury. Burns Open. 2018;2(1):17-34. 2. Wagstaff MJD, Salna IM, Caplash Y, Greenwood JE. Biodegradable Temporising Matrix (BTM) for the reconstruction of defects following serial debridement for necrotising fasciitis: A case series. Burns Open. 2019; 3:12–30. 6. Data on file. 3. Wagstaff MJD, Schmitt BJ, Coghlan P, Finkemeyer JP, Caplash Y, Greenwood JE. A biodegradable polyurethane dermal matrix in reconstruction of free flap donor sites: a pilot study. ePlasty 2015; 15:102–18.

4. Greenwood JE, Dearman BL. Split-skin graft application over an integrating, biodegradable temporising polymer matrix: immediate and delayed. J Burn Care Res 2012; 33(1):7– 19. ® PolyNovo and NovoSorb are registered trademarks of PolyNovo Biomaterials Pty Ltd.

Complex Refractory Wounds: How to Overcome Treatment Recalcitrance and Restore the Healing Trajectory Using Innovative Bioactive Glass Editorial Summary This case series evaluates the efficacy of a novel borate-based bioactive glass wound matrix (BGWM) for treating complex, refractory chronic wounds that failed to heal with multiple previous advanced therapies. Chronic non-healing wounds pose a significant health burden, and new treatment approaches are needed. BGWM is a biocompatible, water-soluble matrix designed to support wound healing. Patients with longstanding surgical and radiation wounds of mean 13.2 month duration were treated with serial BGWM applications per a standardized protocol. Despite previously proving recalcitrant to other costly advanced wound care modalities, all three wounds achieved complete closure after a mean of 8.1 weeks of BGWM use. The mean initial wound volume of 1.9 cm3 across this cohort highlights the severity of the wounds treated. This small case series provides promising preliminary evidence that the BGWM represents an effective new therapeutic option capable of facilitating healing in complex, chronic wounds refractory to other treatments.

Introduction

T Dr Elvis Castillo Garcia Infectious Diseases and Wound Care Physician, Florida Medical Clinic Wesley Chapel FL, United States

Dr Phuong Thuy Nguyen Infectious Diseases and Wound Care Physician, Florida Medical Clinic Wesley Chapel FL, United States

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he profound clinical and socioeconomic ramifications of chronic, non-healing wounds continue to escalate at an alarming rate, representing one of the most formidable challenges facing modern healthcare systems globally. It is estimated that chronic wound prevalence now afflicts over 6 million individuals in the United States alone, culminating in a heavy annual economic burden exceeding $50 billion in associated treatment costs.1,2 This fiscal strain is projected to intensify further as our population ages, with a concurrent rise in age-related comorbidities like diabetes mellitus, obesity, and cardiovascular disease that critically impair physiologic wound healing pathways.3 Implementing advanced, cost-effective wound care strategies that synergistically target the multifactorial impediments underlying each phase of chronic wound pathogenesis is therefore imperative to promote timely and durable healing while reducing downstream healthcare utilization and expenditures.

A novel borate-based bioactive glass wound matrix (BGWM) , (Mirragen® Engineered Tissue Solutions, MO) composed of watersoluble borate compounds has recently emerged as a promising potential solution, demonstrating notable capabilities to facilitate healing in complex chronic wounds based on initial clinical experiences.2 This novel biomaterial represents a distinctly engineered class of biocompatible, biodegradable wound dressings designed to temporarily integrate into the wound microenvironment and

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support native wound repair processes over a finite resorption period.5 Herein, we present our preliminary clinical experience evaluating the safety, tolerability, and therapeutic efficacy of BGWM in treating a series of complex, recalcitrant chronic wounds that had proven refractory to a multitude of other advanced wound care strategies and costly interventions over an extended period.

Chronic wounds are detrimental to patient quality of life and a significant strain on the healthcare economy.1 To reduce healthcare utilization, use of advanced wound care products that address essential components of the healing phases of chronic wounds is critical. A recently developed novel boratebased bioactive glass wound matrix (BGWM) has been shown to facilitate healing in complex chronic wounds.2 Borate-based bioactive glasses are biocompatible water-soluble materials that have been formulated to degrade in a wound over a period of days or weeks. These bioactive glasses have shown promise in wound

Complex Refractory Wounds: Innovative Bioactive Glass Wound Matrix

“Steroids have wide-ranging metabolic effects that hinder key phases of healing— inflammation, proliferation, and remodelling. Determining appropriate candidacy for steroidal therapy requires assessing individual disease state, risk factors, and benefitrisk profile.”

healing.3-5 We report our experience with application of BGWM in recalcitrant, nonhealing wounds previously treated with multiple advanced wound care modalities.

Radiation exposure can significantly impair and delay the normal healing process of tissues and organs.6 When ionizing radiation interacts with cells, it can directly damage DNA structure as well as produce free radicals that attack cell membranes and intracellular proteins and enzymes. This cellular damage triggers programmed cell death (apoptosis) and impairs cellular reproduction.7 Additionally, radiation prompts inflammatory responses that can persist chronically. These effects inhibit the major phases of healing—inflammation, proliferation, and remodelling.

During the inflammatory phase, radiation diminishes the immune cells crucial for debris removal and fighting infection.8 Key growth factors and cytokines for new tissue formation are reduced while inflammatory factors like TGF-beta are elevated. In the proliferative phase, cell reproduction is constrained, slowing replacement of dead cells with viable ones.9 Angiogenesis is also hampered, decreasing oxygen and nutrient supply. Cells may persist in a prolonged state of metabolic stress. In remodelling, radiation causes decreased production and disorganization of the extracellular matrix while increasing stimulators of fibrosis like fibrocytes.9 The result is scar tissue formation rather than healthy replacement tissue.

The healing impairments from radiation are dose-dependent—higher exposures progressively inhibit healing capacity. The timing of radiation delivery can also influence effects, with continual exposures being more damaging than fractionated. Different

tissues display varying radiation sensitivity, related to their baseline regeneration ability and proportion of radiosensitive stem cells.10 However, the mechanisms of radiation-delayed healing are consistent across tissues. Effective strategies to mitigate radiation-impaired healing include limiting radiation dose and avoiding repeat exposures where feasible. Growth factors, stem cell therapies, oxygen radical scavengers, and pharmacologic anti-inflammatories hold promise to help kick-start the recovery process.

Still the impact of radiation on healing should not be underestimated. Radiation protection principles and testing of regenerative biologics are key frontiers requiring further research and development. In healthcare, corticosteroids such as fluticasone, budesonide, hydrocortisone, and prednisone are commonly used for their anti-inflammatory and immunosuppressive properties. However, medicinal steroid use can significantly impair and delay the normal wound healing process.11 Steroids have wideranging metabolic effects that hinder key phases of healing—inflammation, proliferation, and remodelling. Determining appropriate candidacy for steroidal therapy requires assessing individual disease state, risk factors, and benefit-risk profile.

Inflammatory Bowel Diseases Steroids are a foundational treatment for acute phases of inflammatory bowel diseases like Crohn’s and ulcerative colitis. Oral steroids like prednisone offer rapid reprieve from flareup symptoms like abdominal pain, frequent loose stools, bleeding, and malnutrition. They induce remission in moderate or severely active IBD before transitioning patients to maintenance treatments. Caution is warranted in IBD patients with higher complication risks including osteoporosis, diabetes and glaucoma.12

Chronic Obstructive Pulmonary Disease Inhaled corticosteroids like fluticasone and

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Complex Refractory Wounds: Innovative Bioactive Glass Wound Matrix

“Even minor wounds can demonstrate notable failure to progress through the overlapping healing stages. Strategies to restore healing progression include steroid tapering, switching to less potent steroids, and wound environment modification through moisture balance and debridement.”

budesonide are central to managing COPD symptoms and reducing exacerbation frequency.

Oral steroids are deployed intermittently for COPD exacerbations to relieve acute respiratory distress without accentuating comorbidity risks associated with long-term oral steroid use. Contraindications include uncontrolled infections and avoidance in patients with significant untreated tuberculosis risk factors.13

be rebuilt.

The dose and duration of steroid exposure correlates with the severity of healing impairment—higher doses and longer usage most significantly delay healing capacity. The potency of the particular steroid also matters, as does administration route. Inhalational and topical steroids exert more localized effects on wounds than systemic treatment.

Collagen Vascular Diseases Autoimmune disorders like rheumatoid arthritis, systemic lupus erythematosus, granulomatosis with polyangiitis and polymyalgia rheumatica are all responsive to steroids. Intramuscular or intraarticular steroid injections can provide localized efficacy. However, ubiquitous comorbidities and immune status in this population necessitates prudent consideration before sustained high dose systemic steroid administration. First line treatments are often steroid-sparing alternatives like DMARDS or biologics when feasible to minimize exposure.

In the inflammatory phase, steroids blunt the acute immune response needed to clear debris and prevent infection. They reduce key innate immune cells like macrophages and neutrophils and inhibit new vessel permeability. Steroids also lower growth factor and cytokine levels critical to signaling tissue regeneration while raising immunosuppressive factors like IL-10 and lipocortin-1.

In the proliferative phase, cellular reproduction slows under steroid influence, constraining replacement of damaged tissue. Steroids make cells less responsive to growth stimuli and more susceptible to apoptosis. Reduced angiogenesis also limits blood and nutrient supply to heal the wound area. Remodeling is impacted through decreased collagen production and impaired crosslinking, leading to weaker scar tissue formation. Matrix metalloproteinases break down scaffolding proteins faster than they can

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Wounds with greater baseline severity may be most vulnerable to further steroid-induced delay. However, the mechanisms depressing healing are consistent across wound types.

Chronic ulcers and lacerations heal slowly anyway and are pushed to further stagnation.

Even minor wounds can demonstrate notable failure to progress through the overlapping healing stages. Strategies to restore healing progression include steroid tapering, switching to less potent steroids, and wound environment modification through moisture balance and debridement. Growth factors may also aid cellular proliferation as may supplemental nutrition. Still, the multilevel impacts of steroids on recovery pathways should not be underestimated. Further research into therapeutics to counteract steroid-mediated healing retardation remains vital.

In summary, steroids remain a potent weapon against inflammatory states across varieties of conditions and patient profiles. Determining appropriateness requires carefully weighing their immunosuppressive effects against their anti-inflammatory benefits for each patient’s situation. The therapeutic index demands judicious dispensing to maximize relief while minimizing adverse events.

Methods This prospective case series was conducted at our outpatient wound care center between January 2022 and August 2022. All patients

Complex Refractory Wounds: Innovative Bioactive Glass Wound Matrix provided informed consent, and the study was approved by the institutional review board. Patients were eligible if they had a chronic wound that failed to achieve >40% wound area reduction after >4 weeks of appropriate treatment with advanced wound care products. Exclusion criteria included uncontrolled diabetes (HbA1c >9%), untreated malignancy, end-stage renal disease, active immunosuppression, and wounds of vascular or arterial etiology.

Three patients with a total of 3 chronic wounds meeting inclusion criteria were treated with serial applications of BGWM over the study period. All patients underwent initial wound preparation involving sharp debridement of necrotic tissue and cleansing with sterile saline solution. BGWM* was comprised of bioactive borate glass fibers suspended in an aqueous gel matrix (95% type 45S5 bioactive glass).

To apply BGWM, the fibers were first spread evenly across the wound bed to fully contact and cover the entire wound area with a 3-4 mm overlap extending onto the peri-wound skin.

An occlusive secondary dressing was applied over the BGWM to immobilize the matrix and absorb wound exudate. Dressings were changed once weekly during follow-up visits when the wound and surrounding skin were reassessed and the BGWM reapplied as needed until complete wound closure. Systemic antibiotics were prescribed based on clinical criteria for evidence of wound infection.

Wound surface area and volume measurements were obtained using standardized wound imaging and analysis software at each dressing change. Pain levels were self-reported by patients on a 10-point scale. Healing was defined as full re-epithelialization of the wound surface.

Figure 1-3 : Patients in the study showing pre and post BGWM results.

1a

1b

2a

Results The mean age of the patients was 72 years (range 56-84 years). Two of the wounds were chronic, recalcitrant post-surgical wounds and one a chronic radiation wound. All three wounds in this series had failed healing despite multiple previous advanced wound care

2b

3a

3b

modalities including negative pressure wound therapy, bioengineered skin substitutes, and hyperbaric oxygen over a mean duration of 13.2 months (range 8-22 months). The mean initial wound size surface area and volume at the start of BGWM application were 12.7 cm2 (range 5.8-25.6 cm2) and 1.9 cm3 (range 0.8-4.1 cm3), respectively.

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Complex Refractory Wounds: Innovative Bioactive Glass Wound Matrix

“Restoring adequate perfusion and oxygenation is critical for preventing oxidative stress, facilitating inflammatory cell influx, and supporting metabolic demands of wound healing pathways.”

All three wounds achieved complete closure after a mean duration of 8.1 weeks (range 5-11 weeks) with serial BGWM applications as the primary wound treatment. Figures 1-3 illustrate the sequence of healing in each case.

Mean patient-reported pain scores decreased from 6.7/10 at baseline to 1.3/10 after two weeks of BGWM application. BGWM was well tolerated by all patients without any adverse events. Two wounds required a short course of oral antibiotics early in treatment for clinical signs of superficial infection prior to achieving closure.

Discussion The results of this case series demonstrate the promising potential of the borate-based bioactive glass wound matrix (BGWM) as an effective new therapeutic modality for complex, chronic wound pathologies that have proven recalcitrant to other advanced treatment approaches. Despite the inherent challenges to wound healing posed by the advanced age and significant comorbidities afflicting the patients in this cohort, complete wound closure was ultimately achieved in all three cases after a mean of just 8.1 weeks of treatment with serial BGWM applications. This noteworthy outcome is rendered even more remarkable given that these non-healing wounds had persisted for a mean duration of 13.2 months and remained stubbornly refractory to multiple previous advanced wound care therapies and surgical interventions at considerable healthcare expense.

While the small sample size and lack of a control arm preclude definitive conclusions, these preliminary findings align with the

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hypothesized wound healing capabilities ascribed to borate-based bioactive glass.

Complex Refractory Wounds: Innovative Bioactive Glass Wound Matrix Looking ahead, it is imperative that results from this promising initial case series catalyze larger, rigorously-designed randomized controlled trials to definitively establish the clinical efficacy of BGWM compared to current standards of care and other advanced wound care products. Systematic cost-effectiveness and quality of life analyses will also be essential to evaluate the full socioeconomic impact and patient-centered outcomes associated with implementing this novel therapy into chronic wound management protocols. Only through judicious evidence-based validation can the full clinical potential of borate-based bioactive glass wound matrices be realized.

Considerable opportunities remain for continued innovation to further optimize composition, structural properties, and therapeutic delivery of bioactive glass wound matrices. For instance, rational design of hybrid biomaterial composites can impart complementary wound healing capabilities like soft tissue filler or guided tissue regenerative functions. Controlled-release drug delivery systems could be engineered into the resorbable glass matrix for localized administration of

organic compounds like antimicrobials or biomolecules like growth factors and stem cells. As our understanding of chronic wound pathophysiology and the mechanisms by which bioactive glasses interact with wound environments grows, these next-generation wound dressings can be fine-tuned to present a personalized, diseased tailored therapy based on the distinctive wound characteristics and patient risk profile.

In conclusion, this preliminary case series provides compelling initial insights into the promising capacity of a borate-based bioactive glass wound matrix (BGWM) to overcome barriers to healing in complex, chronic wound pathologies that have remained refractory to other advanced treatment modalities. While inherent limitations preclude definitive conclusions, the ability to achieve full wound closure relatively rapidly in this cohort despite formidable challenges posed by patient age, comorbidities, and recalcitrance to previous therapies suggests BGWM may represent a powerful new tool in the wound care armamentarium. Larger, rigorously designed clinical trials are urgently warranted to comprehensively delineate the full therapeutic potential, patient outcomes, health economic impacts, and appropriate clinical utilization of this innovative biomaterial wound matrix therapy.

References 1. Sen CK. Human Wound and Its Burden: Updated 2020 Compendium of Estimates. Adv Wound Care (New Rochelle). 2021;10(5):281-292.

2. Armstrong DG, Orgill DP, Galiano RD, et al. A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. Int Wound J. 2022 May;19(4):791-801.

3. Jung S, Day T, Boone T, et al. Anti-biofilm activity of two novel, borate based, bioactive glass wound dressings. Biomed. Glasses 2019; 5:67–75.

4. Rahaman MN, Day DE, Bal BS, et al. Bioactive glass in tissue engineering. Acta Biomater.

2011; 7(6): 2355–2373.

5. Mehrabi T, Mesgar AS, Mohammadi Z. Bioactive Glasses: A Promising Therapeutic Ion Release Strategy for Enhancing Wound Healing. ACS Biomater Sci Eng. 2020;6(10):53995430.

6. Haubner, Frank, et al. “Wound Healing after Radiation Therapy: Review of the Literature.”

Radiation Oncology, vol. 7, no. 1, 24 Sept. 2012, https://doi.org/10.1186/1748-717x-7-162.

7. Orlita-Kozar, Angelika, et al. “Biological Adaptations of Three-Cells to Radiation Therapy.”

Frontiers in Oncology, vol. 11, 24 Nov. 2021, https://doi.org/10.3389/fonc.2021.718636.

8. Wunderlich, Roland, et al. “Ionizing Radiation Reduces the Capacity of Activated Macrophages to Induce T-Cell Proliferation, but Does Not Trigger Dendritic Cell-Mediated Non-Targeted Effects.” International Journal of Radiation Biology, vol. 95, no. 1, 21 Aug. 2018, pp. 33-43, https://doi.org/10.1080/09553002.2018.1490037.

9. Dormand, Emma-Louise, et al. “Radiotherapy and Wound Healing.” International Wound Journal, vol. 2, no. 2, June 2005, pp. 112–127, https://doi.org/10.1111/j.1742-4801.2005.00079.x 10. Ottomeyer, M., Mohammadkah, A., Day, D., & Westenberg, D. J. (2016). Broad-spectrum antibacterial characteristics of four novel borate-based bioactive glasses, Advances in

11. Wray, P. (2011). “Cotton candy” that heals? Borate glass nanofibers look promising.

American Ceramic Society Bulletin, 90(4), 25-29.

12. Hu, S., Chang, J., Liu, M., & Ning, C. (2009). Study on antibacterial effect of 45S5 Bioglass®. Journal of Materials Science: Materials in Medicine, 20(1), 281-286. https://doi. org/10.1007/s10856-008-3564-5 13. Romano, C. L., Logoluso, N., Meani, E., Romanò, D., De Vecchi, E., Vassena, C., & Drago, L. (2014). A comparative study of the use of bioactive glass S53P4 and antibioticloaded calcium-based bone substitutes in the treatment of chronic osteomyelitis: a retrospective comparative study. The Bone & Joint Journal, 96-B(6), 845-850. https://doi. org/10.1302/0301-620X.96B6.33360 14. Lin, Y., Brown, R. F., Jung, S. B., & Day, D. E. (2014). Angiogenic effects of borate glass microfibers in a rodent model. Journal of Biomedical Materials Research Part A, 102(12), 44914499. https://doi.org/10.1002/jbm.a.35120 15. Zhao, S., Li, L., Wang, H., Zhang, Y., Cheng, X., Zhou, N., Rahaman, M. N., Liu, Z., Huang, W., & Zhang, C. (2015). Wound dressings composed of copper-doped borate bioactive glass microfibers stimulate angiogenesis and heal full-thickness skin defects in a rodent model. Biomaterials, 53, 379-391. https://doi.org/10.1016/j.biomaterials.2015.02.112 16. Jia, T. B., Fu, T., & Liu, J. (2019). The effects of copper-doped borosilicate bioactive glass on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. Journal of Biomaterials Applications, 33(7), 1005-1018. https://doi. org/10.1177/0885328218815770

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Wound Masterclass Video

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Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing for Patients with Pyoderma Gangerosum Ulcers?

Editorial Summary This prospective study evaluates the efficacy of a novel borate-based bioactive glass wound matrix (BGWM) in the treatment of chronic, non-healing pyoderma gangrenosum (PG) ulcers. The primary objective is to assess the impact of BGWM on wound healing trajectories, pain management, and overall clinical outcomes in patients with refractory PG ulcers who have failed numerous prior treatments. By enrolling patients with longstanding, treatment-resistant PG lesions, the study aims to determine whether BGWM can overcome the challenges associated with this debilitating condition. This investigation holds promise for identifying an effective therapeutic approach for a notoriously challenging disease process, with implications for improving quality of life for patients suffering from chronic, non-healing PG ulcers.

Introduction

P

yoderma gangrenosum (PG) is a rare inflammatory skin disease, commonly associated with severe pain with significant morbidity for patients’ lives. PG is characterized by this specific, severe pain, tenderness, and the formation of necrolytic ulcers, significantly impacting patients’ quality of life. This condition poses a significant challenge in management, necessitating a delicate balance between addressing the underlying inflammation and pain while providing optimal wound care. Conventional therapies often target a broad spectrum of immunologic mediators and inflammatory cells implicated in the pathogenesis of PG, including cytokines, neutrophils, and lymphocytes.1 Despite advancements in our understanding of PG, many cases unfortunately still remain refractory to standard treatments, prompting the exploration of novel therapeutic approaches. Treatment is challenging and involves management of inflammation and pain, balanced with optimising wound care.

Therapies typically target a broad spectrum of immunologic mediators and inflammatory cells shown to be involved in PG, including cytokines, neutrophils, and lymphocytes.1 A novel borate-based bioactive glass wound matrix (BGWM) (Mirragen® Engineered Tissue Solutions, MO) has been shown to facilitate healing in complex chronic wounds.2-7 Bioactive glasses are biocompatible water-soluble materials, formulated to quickly degrade in a wound.8-9 Recent studies have highlighted the potential of a borate-based bioactive glass wound matrix (BGWM) in facilitating healing in complex chronic wounds.2-7

Dr Luis A. Laurentin-Perez Hand and Upper Extremity Surgeon, Hand Care Specialists of Wesley Chapel, LLC Wesley Chapel FL, United States

Dr Donald W. Buck II

Mr Dagoberto Rivera

Plastic Surgeon, Specialist in Aesthetic and Reconstructive Surgery of the Face, Breast, Body, and Lipedema

Family Nurse Practitioner at Hyper Healing, LLC Tampa FL, United States

St Louis MO, United States

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Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing?

Signs and Symptoms of Pyoderma Gangrenosum: 1 • • • • • • •

Painful, necrolytic skin ulcers Rapidly enlarging pustules or nodules Lesions can develop at sites of trauma/injury Fever, malaise, and other systemic symptoms Ulcers most commonly on the legs Severe pain and tenderness out of proportion to ulcer size Surrounding erythema and edema

Pyoderma Gangrenosum (PG): The Relentless Challenge of Wound Reconstruction Pyoderma gangrenosum (PG) is characterized by the rapid onset of painful, necrolytic ulcers. These ulcers possess a distinct clinical presentation, with a characteristic pathophysiological features of an undermined border and a violaceous hue. However, the underlying pathophysiology of PG remains enigmatic, further compounding the challenges associated with its management and wound reconstruction. PG is often a diagnosis of exclusion and is often reached at the end of the clinical differential diagnosis list.

The Multifaceted Etiology of PG While the exact etiology of PG remains elusive, it is believed to be a manifestation of dysregulated immune function, driven by a complex interplay of genetic, environmental, and immunological factors. PG is frequently associated with underlying systemic diseases, such as inflammatory bowel diseases (IBD), rheumatoid arthritis, and hematological malignancies, further complicating the clinical picture and treatment approaches. 10

The Vicious Cycle of Inflammation and Tissue Destruction PG is characterized by a self-perpetuating cycle of inflammation and tissue destruction, fueled by the infiltration of neutrophils and other inflammatory cells into the affected areas. This relentless inflammatory response leads to the progressive breakdown of skin and subcutaneous tissues, resulting in the formation of deep, undermined ulcers that are notoriously resistant to healing.

The Challenges of Wound Reconstruction Wound reconstruction in PG presents a formidable challenge for clinicians and patients alike. The aggressive nature of the disease, coupled with the potential for pathergy (the phenomenon where trauma or injury can induce the formation of new lesions), often renders conventional wound management strategies ineffective.

Conventional Therapies: A Balancing Act The mainstay of PG treatment involves a multidisciplinary approach, combining systemic immunomodulatory therapies, such as corticosteroids, cyclosporine, and biologic agents, with meticulous wound care. However, this delicate balance between suppressing the underlying inflammation and promoting wound healing is often precarious, as excessive immunosuppression can impede the body’s natural healing processes. 11

Adjunctive Wound Care Strategies To combat the challenges of wound reconstruction in PG, clinicians have explored various adjunctive wound care strategies, including negative pressure wound therapy (NPWT), hyperbaric oxygen therapy, and the use of advanced wound dressings and skin substitutes. While these approaches may facilitate wound healing in some cases, their efficacy remains variable, and their long-term success is often hampered by the recalcitrant nature of PG. 11 Given the immune-mediated nature of this condition, bioactive glass matrices should be considered as a viable treatment option.

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Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing?

Key Diagnostic Features: 1 • • • • • • •

Rapidly enlarging, painful ulcer with violaceous border Pathergy phenomenon Cribriform or “wrinkled paper” peripheral pattern Exclusion of other causes like infection, malignancy, vascular disease Serosanguinous or purulent drainage Deeper ulcers may involve muscle, fascia, or even bone Associated with underlying systemic diseases

The Promise Approaches

of

Novel

Therapeutic

Recent years have witnessed a surge in research exploring novel therapeutic approaches for PG, driven by the urgent need for more effective and targeted interventions. These include the investigation of targeted biologic agents, stem cell therapies, and the use of innovative biomaterials engineered to modulate the wound healing environment.12

One such promising avenue is the exploration of bioactive glass-based wound matrices, which have demonstrated the ability to provide a conducive environment for healing. 2-7

Figure 1: Borate-based bioactive glass matrix versatility properties.

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“The bioactive glass skin substitute matrix represents a remarkable advancement in the field of tissue regeneration, drawing upon decades of research and clinical application.

Originally developed in the late 1960s by pioneering scientists, this bioactive glass material was engineered to facilitate bone-to-bone bonding and support healing processes, a revolutionary concept at the time.”

Study Aims and Objectives The primary aim of this pioneering study was to evaluate the efficacy of BGWM in the management of chronic, treatment-resistant PG ulcers.

Specifically, we sought to assess the impact of BGWM on: • • • •

Wound healing trajectories Monitoring wound size reduction Monitoring wound depth Monitoring the emergence of granulation tissue

Additionally, we aimed to evaluate the potential of BGWM in alleviating the severe, debilitating pain associated with PG ulcers, which can profoundly impact patients’ quality of life.

Furthermore, this study sought to explore the potential mechanisms through which BGWM may exert its therapeutic effects in the context of PG. We hypothesized that the unique properties of BGWM could modulate the dysregulated inflammatory response characteristic of PG, thereby facilitating wound healing. Moreover, we aimed to observe the potential of BGWM to promote angiogenesis and stimulate tissue regeneration, processes critical for the successful resolution of chronic, non-healing wounds.

profile with no reported adverse events.

Building upon this solid foundation, further investigative efforts have expanded the frontiers of bioactive glass technology, unlocking its potential for soft tissue repair and regeneration across a wide array of clinical domains. Notably, the MIRRAGEN® formulation has emerged as a promising solution for acute and chronic wound management, harnessing the material’s inherent properties to modulate the complex wound healing environment. Moreover, ongoing research continues to explore the use of bioactive glasses in nerve regeneration, dental materials, antimicrobial surfaces, bone grafting, and hemostatic devices, underscoring the vast therapeutic potential of this versatile class of biomaterials.6 Bioactive Glass Wound Matrix.

The bioactive glass skin substitute matrix represents a remarkable advancement in the field of tissue regeneration, drawing upon decades of research and clinical application.

Originally developed in the late 1960s by pioneering scientists, this unique material was engineered to facilitate bone-to-bone bonding and support healing processes, a revolutionary concept at the time.

Over the past five decades, its orthopedic applications have been rigorously tested and refined, establishing an exceptional safety

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Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing?

“As we delve deeper into the intricacies of tissue repair and regenerative medicine, the bioactive glass skin substitute matrix stands as a testament to the synergy between scientific innovation and clinical translation, offering new avenues for enhancing patient outcomes and revolutionizing wound care practices.” 7

Methods

Patient Selection

Study Design

This study enrolled three patients presenting with a total of eight chronic PG ulcers that had proven refractory to numerous prior treatments over an extended duration. Patients were carefully screened to ensure they met the diagnostic criteria for PG 13 and had a failed course of conventional treatment modalities without achieving satisfactory outcomes. Three patients with eight different PG ulcers were treated.

This was a prospective, pilot study designed to evaluate the efficacy and safety of a novel borate-based bioactive glass wound matrix (BGWM) in the management of hard-to-heal pyoderma gangrenosum (PG) ulcers. Stringent inclusion criteria were applied to ensure participants met the diagnostic criteria for PG as outlined by the International Pyoderma Gangrenosum Network. 13 Step A: The wound underwent debridement, and BGWM was placed against the wound bed, bolstered and covered with appropriate dressing to manage moisture.

Step C: BGWM acts as a degradable scaffold for the soft tissue.​It can be applied more than once, and it is fully resorbed in a few weeks.

Additionally, all patients had failed to achieve satisfactory outcomes despite exhausting multiple conventional treatment modalities, including systemic immunosuppressive agents, biologic therapies, and advanced wound care strategies over an extended duration.

Wound Preparation and BGWM Application

Step B: Porous fiber matrix allows for cells and fluids to enter. ​

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Prior to BGWM application, the wounds were meticulously cleansed using a sterile wound cleansing solution to remove any debris, exudate, or necrotic tissue that could impede healing. The BGWM was then carefully shaped and contoured to fit the precise dimensions of each individual ulcer, ensuring adherence and contact with the entire wound surface. To secure the BGWM in place and manage exudate, a non-adherent dressing in combination with an alginate or a super-absorbent foam dressing with gauze was applied as a secondary dressing. The BGWM was reapplied on a weekly basis, with ongoing monitoring and assessment of wound progression, pain levels, and any potential adverse events.

Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing?

“The application of BGWM yielded promising results in this cohort of patients with longstanding, treatment-refractory PG ulcers. Notably, all previously non-healing wounds in this series were returned to a healing trajectory following the introduction of BGWM therapy. The matrix was easy to apply and was used until complete wound closure was achieved for all ulcers.”

Results The application of BGWM yielded promising results in this cohort of patients with longstanding, treatment-refractory PG ulcers.

Notably, all previously non-healing wounds in this series were returned to a healing trajectory following the introduction of BGWM therapy.

The matrix was easy to apply and was used until complete wound closure was achieved for all ulcers. Patients tolerated the BGWM well, with no reported adverse events or complications.

Remarkably, all patients reported significant reductions in pain levels associated with their PG ulcers, a testament to the potential analgesic properties of BGWM. Furthermore, no systemic antibiotic therapy was required during the course of treatment.

in this prospective pilot study demonstrated promising results for the management of chronic, treatment-resistant pyoderma gangrenosum (PG) ulcers. The study enrolled three patients with a total of eight PG ulcers that had failed to respond to multiple conventional therapies over an extended period.

The encouraging outcomes observed in this study suggest that BGWM may offer a promising therapeutic approach for managing chronic, treatment-refractory PG ulcers.

The progression of severe wounds after BGWM application was documented through this mini case series of images (Figures 2-4). One patient’s lower leg and foot wounds showed a marked improvement over a 4-week period, initially presenting as a painful, refractory PG that did not respond to treatment (Figure 2a). The wound showed signs of product integration (Figure 2b-c) before decreasing in size at 3 weeks (Figure 2c) and fully healing at 4 weeks (Figure 2d). Another patient with a partial necrolytic skin ulcer refractory to treatment (Figure 3a) demonstrated progressive healing at 1 week (3b) and 16 weeks (3c) postapplication. Additional patient cases showcased the effectiveness of BGWM in treating rapidly enlarging ulcers (Figure 4a-b), painful ulcers with deeper central defects (Figure 4c-d), interdigital PG extending from the dorsal wound space to the dorsum of the foot (Figure 4e-f), and lateral malleolar PG causing localized scarring, pain, and induration before and after treatment with BGWM is shown (Figure 4g-h).

The results of the application of the boratebased bioactive glass wound matrix (BGWM)

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Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing?

Figure 2a: Patient 1 This patient had refractory Pyoderma Gangrenosum which had not responded to treatment

2a

Figure 2b: Post-application day 1 Wound shows signs of product integration

Figure 2c: Post-application 3 weeks The defect on close monitoring has decreased in size

2c

2b

Figure 3a: Patient 2 Patient has a painful, necrolytic, skin ulcer refractory to treatment.

Figure 2d: Post-application 4 weeks The wound has fully healed

2d

Figure 3b,c: Patient reviewed at standard post-application weekly intervals with appearances at 8 weeks (3b) and 16 weeks (3c) placeholder

3a

3b

3c

Figure 4a,b: Patient 3 Rapidly enlarging ulcer over lateral border of foot, induration present. Before and after treatment with BGWM

Figure 4c,d: Large painful ulcer extending over medial malleolar area, with a deeper central defect and features of chronicity.

Before and after treatment with BGWM

Figure 4e, f: Interdigital PG extending from 1st dorsal wound space to dorsum of the foot affecting toes Before and after treatment with BGWM

Figure 4: Lateral malleolar PG, causing localised scarring, pain and induration.

Before and after treatment with BGWM

4a

4c

4e

4g

4b

4d

4f

4h

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“The application of BGWM yielded resulted in the successful healing of all previously non-healing wounds, with patients experiencing significant pain reduction and no adverse events. The matrix’s ease of application and its ability to facilitate wound clsoure without the need for systemic antibiotics highlight its potential as an adjunctive therapy in the complex management of PG.”

Conclusion Pyoderma gangrenosum remains a formidable challenge in the realm of wound reconstruction and healing, necessitating a multidisciplinary approach that combines targeted immunomodulation with innovative wound care strategies. This prospective pilot study demonstrates the potential of a novel boratebased bioactive glass wound matrix (BGWM) in the management of chronic, treatment-resistant PG ulcers.

The application of BGWM resulted in the successful healing of all previously non-healing wounds, with patients experiencing significant pain reduction and no adverse events. The matrix’s ease of application and its ability to promote wound closure without the need for systemic antibiotics highlight its potential as an adjunctive therapy in the complex management of PG. While these findings are encouraging, further research is needed to fully elucidate the mechanisms underlying the therapeutic effects of BGWM in PG. Future studies should aim to investigate the matrix’s impact on the dysregulated inflammatory response, angiogenesis, and tissue regeneration processes characteristic of PG. Additionally, larger, randomized controlled trials are warranted to validate these initial findings and assess the long-term efficacy and safety of BGWM in the management of PG ulcers.

As we continue to explore novel biomaterials and emerging technologies, the quest for more effective therapeutic interventions for PG remains a priority. The promising results of this study underscore the potential of BGWM as a valuable tool in the armamentarium of wound care specialists, offering new hope for patients suffering from this debilitating condition.

The relentless nature of the disease, coupled with the complex interplay of inflammatory processes and tissue destruction, necessitates a multidisciplinary approach that combines targeted immunomodulation with innovative wound care strategies. While progress has been made, the quest for more effective therapeutic interventions continues, fueled by the promise of novel biomaterials and emerging technologies that may unlock new avenues for managing this debilitating condition. We report our outcomes with use of BGWM in chronic PG ulcers that had failed numerous prior treatments over a prolonged duration.

References 1. Alavi A, French LE, Davis MD, Brassard A, Kirsner RS. Pyoderma gangrenosum: An update on pathophysiology, diagnosis and treatment. Am J Clin Dermatol. 2017 Jun;18(3):355372. doi: 10.1007/s40257-017-0251-7. PMID: 28224502.

2. Castillo-Garcia E, Thuy Nguyen P. Complex Refractory Wounds: How to Overcome Treatment Recalcitrance and Restore the Healing Trajectory Using Innovative Bioactive Glass. Wound Masterclass. Volume 3. March 2024.

3. Johnson ML, Armstrong DG, Ortega W. How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers in Geriatric Patients with Multiple Comorbidities?

Wound Masterclass. Volume 3. March 2024.

4. Laurentin LA, Buck DW, Rivera D. Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing for Patients with Pyoderma Gangerosum Ulcers? Wound Masterclass.

Volume 3. March 2024.

5. Armstrong DG, Orgill DP, Galiano RD, et al. A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. IntWound J. 2021;1-11. doi:10.1111/iwj.13675 6. Jung S, Schultz G, Mafiz AI, Bevels E, Jaskula K, Brownell K, Lantz E, Strickland A. Antimicrobial effects of a borate-based bioactive glass wound matrix on wound-relevant pathogens. J Wound Care. 2023 Dec 7;32(12):763. https://doi.org/10.12968/jowc.2023.32.12.763 old 1. Milne J, Searle R, Styche T. The characteristics and impact of hard-to-heal wounds: results of a standardized survey. J Wound Care 2020;29:282-288.

7. Jung S, Day T, Boone T, et al. Anti-biofilm activity of two novel, borate based, bioactive glass wound dressings. Biomed. Glasses 2019; 5:67–75.

8. Rahaman MN, Day DE, Bal BS, et al. Bioactive glass in tissue engineering. Acta Biomater.

2011; 7(6): 2355–2373.

9. Mehrabi T, Mesgar AS, Mohammadi Z. Bioactive Glasses: A Promising Therapeutic Ion Release Strategy for Enhancing Wound Healing. ACS Biomater Sci Eng. 2020;6(10):53995430.

10. Braswell SF, Kostopoulos TC, Ortega-Loayza AG. Pathophysiology of pyoderma gangrenosum (PG): an updated review. J Am Acad Dermatol. 2015 Oct;73(4):691-8. doi: 10.1016/j.jaad.2015.06.021. Epub 2015 Jul 10. PMID: 26253362.

11. Patel F, Fitzmaurice S, Duong C, He Y, Fergus J, Raychaudhuri SP, Garcia MS, Maverakis E. Effective strategies for the management of pyoderma gangrenosum: a comprehensive review. Acta Derm Venereol. 2015 Jul;95(5):525-31. doi: 10.2340/00015555-2008. PMID: 25387526.

12. Cañedo-Dorantes L, Cañedo-Ayala M, Coto-Preciado S, Beltrán-Rodríguez U, SeguraPeña R, García-Peña A, Hernández-Morales M, Serrano-Trasviña E, Ancer-Arellano J, RamosGaribay A. The Role of Stem Cells and Regenerative Medicine in the Treatment of Pyoderma Gangrenosum. Int J Mol Sci. 2021 May 24;22(11):5545. doi: 10.3390/ijms22115545. PMID: 34070460; PMCID: PMC8197129.

This publication was financially supported by ETS. Mirragen Advanced Wound Matrix is intended fo This publication was financially supported by ETS. Mirragen Advanced Wound Matrix is intended for use in the management of wounds, including pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds,surgical wounds, trauma wounds and draining wounds. ETS does not intend to make clinical or performance claims about Mirragen that exceeds its cleared intended use. For complete instructions for use, please visit www.ets123.com, which includes important safety information. r use in the management of wounds, including pressure ulcers, venous ulcers, diabetic ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds and draining wounds. ETS does not intend to make clinical or performance claims about Mirragen that exceeds its cleared intended use. For complete instructions for use, please visit www. ets123.com, which includes important safety information.

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Micromatrix Dermal Repair Powder: A New Option to Manage Irregular Wounds Editorial Summary Surgical management of infected wounds and tissue destruction in diabetic foot cases often involves aggressive debridement and possible amputations. However, this approach can leave wounds with inadequate tissue coverage, requiring further amputations and resulting in unstable foot stumps.

To address these challenges, acellular and cellular skin substitutes have been developed to support tissue repair. Effective surgical management is crucial for diabetic foot treatment and prevention of recurrent ulcers, requiring multiple procedures for limb salvage. Embracing these advancements can significantly improve surgical care and outcomes for diabetic foot patients.

Introduction

in a foot stump that is shorter and hence more unstable.

T

he management of infected wounds with progressive tissue destruction normally consists of surgical debridement and removal of both the soft tissues and the bone portions affected. In many instances, this aggressive approach leads to a minor amputation.

Acellular and cellular skin substitutes have been developed to facilitate and improve the treatment of complex wounds, especially in the presence of extensive tissue loss. They are designed to create a framework for the tissue repair process to build upon.10

Extensive and aggressive surgical debridement may leave wounds with insufficient soft tissue to cover the exposed bone structures. This condition may require, for primary intention closure, a more proximal amputation, resulting

While indications and techniques continue to evolve, effective surgical management of diabetic foot remains an integral component of care as well as for the prevention of recurrent ulceration (Table 1).1

Table 1: Key changes in the knowledge and management of diabetic foot infections in the last 30 years; summary of the authors views.2 Research field

1985

2015

Pathogens

Methicillin-susceptible Staphylococcus aureus, streptococci, Enterobacteriaceae

More multidrug-resistant organisms (MRSA, ESBLs) Predominance of Gram-negative pathogens in (sub)tropical climates

Microbiological diagnosis

Standard cultures, usually of swab specimens

Aerobic and anaerobic cultures of tissue specimens (soft tissue and bone) Molecular microbiology (e.g., PCR) Metagenomics

Imaging

Plain X-rays: scintigraphy (bone, leukocyte scans)

MRI; SPECT/CT; PET/CT

Antibiotic agents

Pencillins; 1st to 3rd generation cephalosporins; some 2nd generation fluoroquinolones

4th/5th generation cephalosporins; carbapenems; 3rd/4th generation fluoroquinolones; linezolid; daptomycin

Route of administration and site of treatment

Initial (sometimes prolonged) intravenous administration, usually in hospital

Mostly oral (sometimes after a brief intravenous course), even in the presence of vascular disease or osteomyelitis; some topical; outpatient except for severe infections or complex treatments

Spectrum of antibiotic therapy

Relatively broad (directed at Gram-positive and Gram-negative pathogens)

Very broad empiric therapy for severe infections; more targeted for mild/ moderate infections and for definitive therapy

Duration of antibiotic therapy

Many weeks for soft tissue infections: ≥6-12 weeks for bone

1-2 weeks for soft tissue infections; 4-6 weeks for osteomyelitis

Surgical approach

Aggressive (ablative) therapeutic surgery; inpatient treatment

More conservative (tissue sparing) therapeutic (even for osteomyelitis) and preventive surgery; corrective surgery; often in outpatient facilities and specialized diabetic foot centres

Revascularization

Open vascular surgery

More percutaneous angioplasty and distal bypasses, including infragenicular

Specialist in Endocrinology, Metabolic Diseases and Diabetology

Management guidelines

Mostly individual, empirical approaches Individual recommendations and practices on the hospital level

Clinical guidelines based on systematic reviews; multidisciplinary teams, especially including podiatry; clinical pathways; some behavioural sciences National guidelines; validation of guidelines

Expert in medical and surgical treatment of Diabetic Foot

Adjunctive treatments

Stimulation with growth factors; platelet-rich products; larval biotherapy (maggots)

Hyperbaric oxygen therapy; granulocyte-stimulating factors; research in stem cell and bacteriophase therapies; microbiomes concepts

Dressing

Simple dressings, with seperate use of disinfection agents

More hydrofibre and silver-containing dressings; studies with topical antibiotics embedded in dressings

Scientific publications

Mostly case series

More prospective randomized trials, multicenter studies, and evidence-based (Cochrane) meta-analyses

Prof Dr Luca Dalla Paola

Ferrara, Italy

ESBL: extended-spectrum beta-lactamase; MRI: magnetic resonance imaging; MRSA: methicillin-resistant Staphylococcus aureus; PET/CT: positron emission tomography/ computed tomography; SPECT/CT: single photon emission computed tomography/ computed tomography

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Micromatrix Dermal Repair Powder: A New Option to Manage Irregular Wounds

“These wounds pose unique challenges and necessitate innovative solutions to promote effective healing and enhance surgical outcomes.”

Diabetic foot surgery is a complex treatment process that often requires multiple procedures (more than 2 or 3) to achieve limb salvage and preserve the affected limb (Figures 1 - 3). One key factor driving the utilization of this product is the presence of undermined or irregular wounds commonly observed in diabetic foot cases. These wounds pose unique challenges and necessitate innovative solutions to promote effective healing and enhance surgical outcomes.

Figure 1: Diabetic Foot Surgery Classification.3

Diabetic Foot Surgery Class

Description

Class IV: Emergent

Procedure performed to limit progression of acute infection

Class III: Curative

Procedure performed to assist in healing open wound

Class II: Prophylactic

Materials and Methods A cohort of diabetic patients was recruited between July 2013 and October 2014 for a study. The inclusion criteria for the study were as follows: patients with active lesions below the ankle level graded as IIIA TUC (Texas University Classification) after undergoing surgical debridement and infection control, and with TcPO2 (transcutaneous oxygen pressure) levels above 30 mmHg.

Class I: Elective

Figure 2:

Potential Risk for High Level Amput

High

Moderate

Procedure performed to reduce risk of ulceration or reulceration in person with loss of protective sensation but without open wound

Low

Procedure performed to alleviate pain or limitation of motion in a person without loss of protective sensation

Very Low

Figure 3:

On the other hand, the exclusion criteria included patients with critical limb ischemia (CLI) who had no options for revascularization, patients with TcPO2 levels below 30 mmHg, those with acute infections, individuals with chronic osteomyelitis but without any surgical treatment, and patients with indications for primary intention closure involving a shorter stump. These criteria were established to ensure the selection of appropriate patients for the study and to focus on specific cases where the intervention could be most beneficial.

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Key Points for Avoiding Amputations

New Tools

Several key components are involved in the comprehensive management of diabetic foot conditions. These include:

Advancements in the field of diabetic foot management have introduced new tools and techniques to improve treatment outcomes.

Some notable additions include:

•

Relief of plantar pressure to alleviate neuropathic plantar ulcers

•

•

Revascularization procedures to improve blood flow to the affected area

New antiseptic agents: The development of novel antiseptic agents provides more effective means of preventing and treating infections in diabetic foot wounds (Figure 4a)

•

Prompt and effective treatment of infected diabetic foot cases

•

•

Surgical interventions for chronic diabetic foot conditions, particularly osteomyelitis

Hydro knives: Hydro knives are specialized surgical instruments that use a high-pressure water stream for precise and controlled debridement of wounds, facilitating better tissue removal (Figure 4e)

•

Surgical management of instability and deformity in neuropathic or Charcot foot

•

•

Utilization of advanced local therapies such as negative pressure wound therapy (NPWT), bioengineered tissues, and external fixation

New offloading devices: Innovations in offloading devices, such as specialized footwear or orthotic devices, help reduce pressure on the foot and protect vulnerable areas from excessive stress, promoting healing and preventing ulcers

•

NPWT with instillation: Negative pressure wound therapy (NPWT) combined with wound instillation involves the application of a vacuum-assisted dressing to the wound, along with the delivery of specialized solutions or medications to promote wound healing and combat infection (Figure 4d)

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Bioengineered tissues: The use of bioengineered tissues, such as artificial skin substitutes or cell-based therapies, offers potential for accelerating wound healing and improving tissue regeneration in diabetic foot ulcers (Figure 4f)

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MicroMatrix® Repair Powder (Integra LifeSciences, Princeton, NJ, United States) is a new product designed to support wound healing by providing a scaffold and growth factors to enhance tissue repair and regeneration (Figures 4g, 4h)

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Patient education and promoting compliance with treatment plans

•

Monitoring and controlling diabetes to maintain optimal blood glucose levels

•

Managing cardiovascular risk factors that may exacerbate diabetic foot complications

•

These aspects form a comprehensive approach to diabetic foot care, addressing various aspects of the condition to optimize treatment outcomes and prevent further complications

Figure 4: 4a: New antiseptic agents.

4b: New offloading devices.

4c: New offloading devices.

4d: NPWT with installation.

4e: Hydro knives.

4f: Bioengineered tissues.

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4g: MicroMatrix Repair Powder.

4h: MicroMatrix Repair Powder.

• •

4a

4b

4c

4d

4e

4f

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These new tools and techniques demonstrate ongoing advancements in diabetic foot management, aiming to enhance treatment options and improve outcomes for individuals with this condition.

Micromatrix Dermal Repair Powder: A New Option to Manage Irregular Wounds Figure 5: Preserving length: the role of advanced therapy. Bio-engineered tissues are useful in improving conservative outcomes in the treatment of the diabetic foot.

5a

5b

5c

5d

5e

5f

5g

5h

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Furthermore, durability is crucial to ensure long-term effectiveness. Lastly, it should be easy to apply and securely adhere to the wound for optimal functionality. These features collectively contribute to an ideal skin substitute that can effectively aid in wound healing and provide optimal patient outcomes.

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Additionally, it should possess properties that resist infection, prevent water loss, and withstand shear forces, thereby minimizing the risk of complications. Cost-effectiveness, wide availability, and a long shelf life are also desirable attributes. The skin substitute should not provoke an immune response (nonantigenic), be flexible in terms of thickness, and capable of conforming to irregular wound surfaces (Figure 6).

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An ideal skin substitute should possess certain key characteristics to effectively promote wound healing. Firstly, it should offer immediate replacement of both the lost dermis and epidermis, ensuring prompt and complete wound coverage.

Figure 6: Integra Collagen: history. More than 10 Million procedures performed with Integra collagen.

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Skin Substitutes

Figure 7: Treatment Protocol.

CLEAN WOUND (after surgical debridement and/ or revascularization

COMPLETE HEALING OR SKIN GRAFT (IF NECESSARY)

NPWT OR NON OCCLUSIVE DRESSING

INTEGRA FLOWABLE

COVERAGE WITH • IDRT • NON OCCLUSIVE DRESSING • SKIN GRAFT

Treatment Protocol The treatment protocol for the management of wounds includes several steps. Initially, surgical debridement is performed, targeting any osteomyelitic foci identified through X-ray and MRI techniques (Figure 7).

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Micromatrix Dermal Repair Powder: A New Option to Manage Irregular Wounds Patient 1:

Patient 2:

Patient 3:

Male 47 yrs

Patient 2: Male 80yrs

Male 80 yrs

Type 1 Diabetes Mellitus

Type 2 DM

Kidney failure stage 5 (peritoneal dialysis)

Kidney transplantation

CLI BTK and PTA of posterior tibial/plantar anterior tibial/dorsalis pedis

CLI no option BTK

CLI with occlusion of ATA and PTA treated with endovascular recanalization of ATA and dorsalis pedis

MRSA

Pseudomonas aeruginosa MDR

Staph Aureus MS

Patient 4:

Patient 5:

Patient 6:

Male 58 yrs

Patient 6: Male 60 yrs

Type 2 DM

Type 2 DM

Dehiscence of third toe with metatarsal osteomyelitis

Staph Epidermidis MR

CLI (total occlusion of SFA Pop and BTK vessels): revascolarization DEB SFA/POP ant PTA Ant TA/Post TA

Osteomyelitis 5^MTPJ and plantar progression

Proteus Mirabilis

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Micromatrix Dermal Repair Powder: A New Option to Manage Irregular Wounds Revascularization is then carried out through percutaneous procedures or bypass to improve blood flow to the affected area. Medical therapy involving antibiotic therapy is administered to combat infection. Offloading, which reduces pressure on the wound, is also implemented.

Next, Negative Pressure Wound Therapy (NPWT) is applied for an average duration of 7 ± 8 days. NPWT helps promote wound healing by creating a vacuum environment that enhances blood circulation and removes excess fluid. Additionally, MicroMatrix® particles are utilized to manage various types of wounds, including partial- and full-thickness wounds, pressure ulcers, venous ulcers, diabetic ulcers, surgical wounds, trauma wounds, and draining wounds. These particles are designed for onetime use.

Finally, if necessary, the wound may undergo application of IDRT (Dermal Regeneration Template, Integra LifeSciences, Princeton, NJ, United States) or a skin graft, either in a onestep or delayed manner, to facilitate the healing process.

wounds, MicroMatrix® is an accessible dermal repair powder that effectively manages such wound types. It provides an easy-to-use solution for wound management.

Biologically derived, non-crosslinked, extracellular matrix (ECM) derived from the lamina propria and epithelial basement membrane (EBM) of the porcine urinary bladder. The Integra UBM™ technology is non-synthetic, minimally processed, and derived products are not associated with an inflammatory response (Figure 8).

UBM (Urinary Bladder Matrix) consists of a three-dimensional structure composed of various collagens and proteins. These components include Collagen Types I, III, IV, and VII, which provide structural support.

UBM also contains Glycosaminoglycans and Proteoglycans, which contribute to its unique composition. Additionally, Laminin, a protein involved in cell adhesion and migration, is present in UBM. These elements collectively contribute to the properties and functionality of UBM in tissue repair and regeneration (Figure 9).

Results Figure 8:

Out of the total cases evaluated (71), a significant percentage (76.6%) successfully healed. Among these cases, a portion (28.8%) achieved healing without the need for surgical coverage. Onestep skin grafting was performed in 35.2% of cases, contributing to their successful healing.

In a smaller subset of cases (12.6%), delayed skin grafting was required for effective wound closure. Additionally, a minor percentage (7.0%) showed improvement in their condition.

A remaining group of cases (16.9%) remained unchanged (N.C.) throughout the evaluation period.

What Is the Scope of Use of Powder Dermal Substitute?

In the evaluated cases, tunneling wounds were not observed. However, deep surgical dehiscence and open amputation wounds were identified and managed accordingly. For Type III A TUC wounds (traumatic, contaminated wounds), skin grafting was employed, which proved beneficial in promoting healing and closure. Additionally, open exostectomy was performed. Overall, the wound healing rate was 87%. To address irregular and undermining

USB Devices Contain: • • • • • •

Clycosaminoglycans Collagen Type I Collagen Type III Collagen Type IV Collagen Type VII Laminin

Epithelial Basement Membrane •

Contains a specialized protein composition, including anchoring-type collagens IV and VII

•

Thin, dense collagen structure ideal for cell attachment and proliferation

Lamina Propria •

Rough and porous surface ideal for cellular infiltration and neovascularization

Figure 9:

Lamina Propria Open and porous surface that allows for cellular infiltration and capillary ingrowth Epithelial Basement Membrane Thin dense collagen structure that may contribute to cell attachment

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Micromatrix Dermal Repair Powder: A New Option to Manage Irregular Wounds UBM devices preserve the epithelial basement membrane, which serves various purposes. It potentially contributes to the body’s regulation of cell growth and immune response patterns.

The presence of collagen VII in the membrane may aid in re-epithelialization, promoting the growth of new epithelial tissue. Additionally, UBM devices have demonstrated the ability to facilitate constructive remodeling processes.

Figure 10: Distinct Host Response to the use of UBM in a Clinical Setting Purpose: Prospective case-control clinical study looking at the macrophage phenotype related M1 and M2 score in the wounds of diabetic subjects compared to that observed in non-diabetic patients when their wounds were managed with Integra UBM wound devices.

TUC grade-II/III Wounds 21%

Patients in the study had a range of wound types including: DFUs, VLUs and Surgical Wounds.

Open amputation 35%

Results:

Surgical wound dehiscence 14%

Diabetic patients in this study exhibited a significantly higher M1:M2 score pre-treatment compared to post-treatment.

The M1:M2 score was reduced to similar levels in both diabetic and non-diabetic patients following UBM wound management.

Statistically significant wound size reduction in both diabetic and non-diabetic patients (35% and 43%, respectively (p<0.05 for both groups).

Open sequestrectomy 30%

Author(s): Frykberg RG et al. Journal of Wound Care. 2016.

Design:

Figure 11: 2nd grade TUC

3rd grade TUC

21.13%

78.87% Peripheral arteriopathy and revascularization 53.52%

8.45%

45.07%

Figure 12:

Prospective, randomized, multi-center, clinical trial interim analysis in the management of neuropathic DFUs. 95 patients at 13 sites entered the study, from which the evaluable data of 56 patients at 8 study facilities were analyzed. Patients were randomized between the MicroMatrix and Cytal Wound Matrix and Dermagraft groups. 27 MMX&CWM and 29 Dermagraft subjects had complete evaluable data at this interim analysis.

The study evaluated the incidence of complete ulcer closure, rate of ulcer healing, wound characteristics, patient QOL, cost effectiveness, and reoccurrence.

No statistically significant differences between patient populations incl. gender, age, race, ethnicity, size of ulcer, ulcer location, diabetes type, and University of Texas Wound Classification System grade.

Regimen: Weekly applications (concomitant use of MMX & CWM 1-Layer) for up to eight 8 weeks or until complete wound closure. A 2-week period of SoC followed the treatment phase, and wound closure was assessed at the end of that period.

Any wounds that completely healed were evaluated at 6 months after initial treatment for evaluation of reoccurrence.

Results/Conclusion (at the planned interim analysis): No statistical difference in incidence of complete closure or the rate of wound closure between the 2 groups.

However, due to the small data set, direct clinical comparisons of safety and efficacy between the 2 groups could not be established. The MMX & CWM group showed statistically significant improvements in QoL measurements, although there was no correlation to any specific clinical variable, when compared to the Dermagraft group.

Finally, the MMX & CWM group showed a statistically lower device cost per subject as compared to the Dermagraft group (see Table 3).

Table 2:

Table 3:

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Micromatrix Dermal Repair Powder: A New Option to Manage Irregular Wounds

Conclusion In conclusion, utilizing UBM technology offers a minimally processed approach that preserves the structural integrity and extracellular matrix (ECM) components. This minimal processing ensures the retention of an intact epithelial basement membrane, which plays a crucial role in supporting cellular infiltration and capillary ingrowth. UBM devices aid the body in facilitating constructive tissue remodeling,

making them potentially beneficial in the treatment of non-infected diabetic foot ulcers (DFUs). By promoting wound healing, UBM technology may help avoid the need for more aggressive and proximal amputations, preserving as much of the affected limb as possible. However, it is essential to emphasize that the utilization of UBM should be part of a comprehensive multidisciplinary treatment program that includes infection control and revascularization.

References 1. Frykberg RG, Wukich DK, Kavarthapu V, Zgonis T, Dalla Paola L. Surgery for the diabetic foot: A key component of care. Diabetes/Metabolism Research and Reviews. 2019 Dec 10;36(S1).

2. Uçkay I, Aragón-Sánchez J, Lew D, Lipsky BA. Diabetic foot infections: what have we learned in the last 30 years? International Journal of Infectious Diseases. 2015 Nov;40:81–91 3. Armstrong, Frykberg, Diabetic Medicine, 2003 4. Dalla Paola L. Confronting a Dramatic Situation. The International Journal of Lower Extremity Wounds. 2014 Aug 14;13(4):247–62.

5. Dalla Paola L, Faglia E. Bentham Science Publisher BSP. Treatment of Diabetic Foot Ulcer: An Overview Strategies for Clinical Approach. Current Diabetes Reviews. 2006 Nov 1;2(4):431–47.

6. Clerici G, Caminiti M, Curci V, Quarantiello A, Faglia E. The Use of a Dermal Substitute (Integra) to Preserve Maximal Foot Length in a Diabetic Foot Wound With Bone and Tendon Exposure Following Urgent Surgical Debridement for an Acute Infection. The International Journal of Lower Extremity Wounds. 2009 Nov 24;8(4):209–12.

7. Ramanujam CL, Zgonis T. Surgical soft tissue closure of severe diabetic foot infections: a combination of biologics, negative pressure wound therapy, and skin grafting. Clinics in Podiatric Medicine and Surgery [Internet]. 2012 Jan 1 [cited 2021 Jul 10];29(1):143–6. Available from: https://pubmed.ncbi.nlm.nih.gov/22243576 8. Dalla Paola L, Cimaglia P, Carone A, Boscarino G, Scavone G. Use of Integra Dermal Regeneration Template for Limb Salvage in Diabetic Patients With No-Option Critical Limb Ischemia. The International Journal of Lower Extremity Wounds. 2020 Feb 14;153473462090574.

9. Fraccalvieri M, G Pristerà, Zingarelli E, Ruka E, Bruschi S. Treatment of chronic heel osteomyelitis in vasculopathic patients. Can the combined use of Integra®, skin graft and negative pressure wound therapy be considered a valid therapeutic approach after partial tangential calcanectomy? 2012 Apr 1;9(2):214–20.

10. Dalla Paola L, Carone A, Vasilache L, Baglioni M, Scaletta V, Pattavina M. Use of a new gel-like dermal matrix for the treatment of diabetic foot ulcers: efficacy study in a population of diabetic patients affected by complicated lower limb lesions

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How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers in Geriatric Patients with Multiple Comorbidities?

Editorial Summary In this retrospective case series, the efficacy of a novel borate-based bioactive glass wound matrix (BGWM) in treating hard-to-heal venous leg ulcers in geriatric patients with multiple comorbidities was evaluated. Patients were selected who had undergone both arterial and venous duplex procedures, with some receiving venous ablation treatments. Prior to BGWM application, wounds were debrided once and cleansed with hypochlorous acid solution. The BGWM was then contoured, tailored and applied directly to the wound bed. The BGWM was secured with a contact layer and skin strips. A super-absorbent fiber dressing was used to manage exudate, and compression dressings were changed twice per week. This retrospective pilot study included patients with an average age of 80.3 years, each presenting with one or more venous leg ulcers and a range of comorbidities. The wounds, present for an average of 15.1 weeks before BGWM application, varied in size from 1.2 to 56.0 cm². Results indicated a significant improvement in wound healing, with all wounds healing within an average of 10 weeks. Pain levels, initially averaged at 5.8/10, were reduced to 0.0/10 after an average of 2.6 dressing changes. The study concluded that BGWM facilitated wound closure, was well tolerated by patients, significantly reduced pain, and did not result in any adverse events or require antibiotics, underscoring its potential as an effective treatment for venous leg ulcers in elderly patients with complex health profiles.

W

ound healing impairment represent a significant clinical challenge in geriatric patients. Age-related physiologic changes predispose the elderly to chronic non-healing wounds. Dermal and epidermal thinning along with decreased elasticity of aged skin increases susceptibility to injury and impairs structural integrity.1 Elderly patients also have decreased mobility, circulation, and sensation, which can delay wound healing. Comorbidities prevalent in this population, including restricted mobility, peripheral vascular disease, neuropathy, and immunosenescence further compromise wound healing potential.2 This paper explores the use of a novel borate-based bioactive glass wound matrix (BGWM) , (Mirragen® Engineered Tissue Solutions, MO) which shows promising results in this patient demographic.

Dr Martin L. Johnson Plastic Surgeon, Wound Care Specialist

Geriatric Patients Face Unique Challenges in Wound Care:

Pomona CA, United States

•

Poor Circulation Age-related arteriosclerosis and vascular stiffening lead to diminished peripheral perfusion and tissue oxygenation. The resultant hypoxic state and impaired delivery of circulating nutrients critically disrupt the physiological milieu required for optimal wound healing processes.3 Chronic diseases that affect circulation like peripheral vascular disease or diabetes compound the problem. Strategies like compression stockings can have an impact to blood flow to wound sites.4

•

Ms Erianthe Ortega

Prof David G. Armstrong

Research Nurse, RN-PHN, BSN

Professor of Surgery and Director, Southwestern Academic Limb Salvage Alliance (SALSA), Keck School of Medicine of USC

Pomona CA, United States

Los Angeles CA, United States

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Thin Fragile Skin The elderly exhibit delayed and disordered repair across all phases of wound healing. Impairments in the inflammatory phase include decreased neutrophil chemotaxis, phagocytosis, and oxidative kill in response to bacterial contamination.3 The proliferative phase is hindered by age-related declines in fibroblast migration, proliferation, and expression of growth factors necessary for angiogenesis and extracellular matrix deposition.4 Finally, re-epithelialization deficits interfere with keratinocyte activation and migration required for re-

How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers

“The complex barriers to healing posed by age necessitate a multifaceted, patient-centered approach. BGWM is a is a bioabsorbable wound matrix composed of borate-based glass fibers. Its composition and structural properties have been intentionally engineered to exhibit biocompatibility and facilitate the body’s innate wound healing cascades. Preclinical and clinical evaluations have demonstrated this matrix to be a safe, effective and efficient therapeutic modality for the management of both acute traumatic wounds as well as complex chronic wound etiologies.”

epithelialization.5 •

Impaired Immunity Chronic wounds in the geriatric population are often complicated by multiple intrinsic and extrinsic factors. Venous stasis ulcers and diabetic foot ulcers are among the most common etiologies.6 These nonhealing wounds significantly impact quality of life, increase risk of infection, amputation, and consume substantial healthcare resources.7 Optimizing local wound care and addressing systemic factors like malnutrition, glycemic control, and vascular insufficiency are crucial to facilitate healing in this challenging patient subset. Older adults are also at increased risk of wound infections, which can quickly become systemic.7 Meticulous wound care technique and early treatment with oral antibiotics combat infections.

•

offloading maneuvers and regular dressing changes for existing wounds. Failure to periodically redistribute pressure and alleviate persistent compression leads to the development of additional pressure injuries. Involvement of skilled nursing personnel to provide comprehensive wound care, including adherence to rigid repositioning schedules, is paramount in preventing further cutaneous deterioration and preserving the integrity of tissues overlying bony prominences in this highrisk cohort.8 The complex barriers to healing posed by age necessitate a multifaceted, patient-centered approach. Individualized nutritional support, infection control, advanced dressings, and pressure redistribution are key elements in effective geriatric wound management. With proper treatment, even chronic wounds can be healed, dramatically improving seniors’ quality of life.

Nutritional Deficits Sufficient protein intake and adequate levels of micronutrients such as vitamins A, C, and zinc are essential requirements for appropriate tissue repair and regenerative processes. Nutritional deficiencies, often seen in the geriatric population due to poor dietary intake or malabsorptive states, can significantly impair wound healing capabilities. Targeted nutritional supplementation with high-calorie, highprotein oral formulations enriched with zinc and vitamin complexes may help restore the metabolic derangements that compromise the body’s reparative mechanisms in this vulnerable patient subset.

Early intervention to return hard-to-heal wounds to a healing trajectory is crucial in improving wound care efficiency.9 Once the patient’s underlying conditions are addressed, there is enhanced benefit for use of advanced products that target specific wound problems.

Use of a recently developed novel boratebased bioactive glass wound matrix* (BGWM) has demonstrated promise in wound healing.10 Bioactive glass materials are biocompatible water-soluble materials that release their ions when submerged in body fluids. We report our experience with application of BGWM in venous leg ulcers of patients with multiple comorbidities.

Arterial and Venous Duplex Procedures •

Reduced Mobility Duplex ultrasonography is an essential vascular Mobility limitations prevalent in the geriatric population critically impede their ability to perform necessary

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How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers study for older adults with compromised circulation. This non-invasive test uses Doppler ultrasonography to visualize blood flow in arteries and veins.

For arterial exams, duplex imaging assesses blood flow volume and velocity to identify blockages or narrowing. Testing of lower extremity arteries helps diagnose peripheral artery disease, a common contributor to poor wound healing in the elderly. However, preexisting wounds may preclude compression which is necessary for valid testing.

Consequently, stricter temperature parameters and temporal limitations must be implemented during endovenous heat delivery in elderly patients undergoing these procedures.

Establishing more conservative maximum temperature thresholds and curtailing the duration of thermal exposure are prudent measures to mitigate the heightened vulnerability to cutaneous burns and deeper soft tissue thermal necrosis in this specific patient subset with compromised anatomic insulation.

•

Venous duplex scans evaluate blood flow, valve competency, and potential clots in leg veins. Chronic venous insufficiency impedes venous return, causing edema and venous leg ulcers.14 Ultrasound mapping locates faulty valves needing repair. But for accurate results, wounds must be completely dry with dressings removed, which risks contamination or trauma to fragile surrounding tissues.

While vascular duplex provides key data to guide treatment, wound issues like infection or fragility may restrict proper scanning.

Clinicians must carefully weigh the risks and benefits of testing, and take precautions to avoid aggravating wounds. With thoughtful preparation and technique, duplex can successfully inform vascular interventions to improve tissue perfusion and healing in the vulnerable elderly population.

Coexisting medical conditions highly prevalent in the geriatric population, such as diabetes mellitus, peripheral vascular disease, and chronic edematous states, further compound the risk profile for potential wound complications associated with endovenous thermal ablation procedures. To mitigate these heightened risks, a more judicious approach to selecting more favorable venous targets and implementing conservative limitations on the extent and magnitude of delivered ablative energy is warranted in elderly patients with these comorbidities.

•

Age-related Dermal Atrophy and Thermal Injury Risk During Endovenous Ablation

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Pharmacological Considerations This patient subset also exhibits an exaggerated sensitivity to sedative and analgesic medications frequently employed during these procedures. Appropriate downward dosage adjustments are therefore requisite to avoid excessive central nervous system depression. Maintaining a relatively lighter plane of sedation allows for continuous monitoring of the patient’s pain perception and facilitates early detection of potential iatrogenic thermal injury during the ablation.

Venous ablation is a minimally invasive technique that uses thermal energy to seal faulty veins causing venous insufficiency.15 While an effective option for younger patients, several factors make venous ablation more complex in the elderly.

The geriatric population exhibits dermal and subcutaneous tissue atrophy, resulting in decreased adipose insulation surrounding superficial leg veins targeted for endovenous thermal ablation procedures. This attenuation of the protective soft tissue layer overlying the venous structures increases the risk of iatrogenic thermal injury to surrounding skin and subcutaneous tissues during the application of tumescent anesthesia and heat-based ablative energies.

Impact of Comorbidities on Procedural Risks

•

Cognitive and Mobility Factors Cognitive deficits associated with neurodegenerative disorders may impair some elderly patients’ capacity to comprehend and comply with critical procedural instructions, such as maintaining immobility during the application of ablative energy. Finally, age-related decrements in mobility and

How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers dexterity commonly afflict the geriatric population, potentially hampering their ability to properly apply and maintain therapeutic compression stockings during the post-procedural period. Transitioning to alternative compression modalities, such as adhesive multi-layer compression bandages or adjustable circumferential compression devices, may enhance selfcare capabilities and improve compliance with this critical aspect of post-ablation management.

Other causative theories include the ‘white cell trapping’ theory, suggesting that white cells, following an episode of deep vein thrombosis or phlebitis, become trapped in the leg’s capillaries. These cells then release toxic substances like oxygen free radicals, causing tissue death. Such underlying issues become evident when any subsequent minor injury to the lower leg area can rapidly lead to ulceration.

Venous leg ulcerations (VLU) most commonly occur around the gaiter area, where the ulcers tend to be shallow.16

With thoughtful precautions including lower energy settings, mild sedation, compression alternatives, and careful monitoring, ablation can still successfully treat venous reflux in elderly patients. However, risks versus benefits must be weighed carefully for each individual.

Improved collaboration with geriatrics teams helps optimize outcomes.

When examining wounds in elderly patients, it is important to move slowly and communicate clearly. Elderly skin is thinner and more fragile, so handle the surrounding area gently. Assess the wound for signs of infection like redness, swelling, drainage, odor, and pain. Consider factors that may delay healing such as poor circulation, nutrition, and mobility. The elderly are at higher risk for skin tears so check carefully for flap tears if tape or bandages are removed.

Evaluate the wound bed for necrosis or eschar formation. Check sensation around the wound for neuropathy which can increase risk. Assess medical history including medications that may interfere with healing. Explain what you are checking for at each step to help ease anxiety.

Keep in mind recovery may be slower so set realistic goals, and follow up more frequently on progress. With patience and care, you can properly examine and treat wounds in the elderly population.

In health, the venous system of the lower leg pumps blood back towards the heart. This action, performed against gravity, is facilitated by three categories of veins: deep, superficial, and communicating (perforator) veins. The superficial veins, including the long and short saphenous veins, pump blood under low pressure into the deep venous system through perforators. The deep veins, surrounded by calf muscles, assist in pumping blood up the leg during walking, aided by the calf muscle pump and full ankle movement, which engages the Achilles tendon.

Methods Damage to the venous system can arise from various conditions, such as deep vein thrombosis and varicose veins, which damage the perforators and make them incompetent.

Additionally, immobility and arthritic changes in the ankle joint can impede venous return.

Failure of the calf muscle pump leads to blood backflow and pooling, resulting in venous hypertension. This condition causes edema in the lower leg and pigmentation in the ‘gaiter’ area due to hemoglobin released from overstretched blood capillaries, depositing haemosiderin. The increased ambulatory pressure may also increase the permeability of the capillary bed, allowing fibrinogen to escape into the interstitial fluid, forming insoluble fibrin complexes that hinder oxygen diffusion to tissues, a condition described by the ‘fibrin cuff theory.’

Patient Selection and Pretreatment Evaluation All patients enrolled in this study underwent comprehensive vascular assessment with arterial and venous duplex ultrasound examinations prior to initiation of treatment. In addition, 3 of the 5 patients had previously undergone venous ablation procedures to treat associated venous insufficiency.

Wound Preparation At baseline, all wound beds were sharply debrided to remove devitalized tissue and create an appropriate environment for wound healing. No patients received systemic antibiotic therapy during the study period.

Wound cleansing prior to each bioengineered glass application consisted of irrigation with a hypochlorous acid solution to reduce bacterial burden.

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How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers

Bioactive Matrix Application The Bioactive Wound Matrix (BGWM) was prepared by trimming to the dimensions required to fully cover the wound area, ensuring a 3-4 mm overlap onto the peri-wound skin. The customized BGWM was then placed in direct contact with the wound bed and immobilized using an adhesive contact layer reinforced with skin strips. A super-absorbent fiber dressing was applied as an outer layer to manage wound exudate. Compression wraps consisting of two layers were applied over the dressings and changed twice weekly at each study visit along with inspection and reinforcement of the underlying BGWM application as needed.

This structured wound care protocol following Figure 1a: Patient with large, right medial, non-healing lower leg defect shown

1a

Figure 3a: Patient with left medial leg non healing wound

3a

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Figure 1b: Patient showing healed, right medial lower leg defect after BGWM application

1b

Figure 3b: Patient with almost complete closure after BGWM application

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established clinical practice guidelines was implemented consistently across all patients to ensure standardization of the bioactive glass application technique.

Results Five patients with six venous leg ulcers were treated. Average patient age was 80.3 (range: 6887) and all patients had multiple comorbidities.

Wounds were present an average of 15.1 weeks prior to initial BGWM application and mean wound size at start of BGWM was 13.5 cm2 (range: 1.2-56.0 cm2). All wounds healed after an average of 10.0 weeks (range: 3-27 weeks) during use of BGWM. Pain on a self-reporting scale was reduced from an average of 5.8/10 to 0.0/10 within an average of 2.6 dressing changes.

Figure 2a: Patient with large, non healing medial leg wound, resistant to other treatment modalities

2a

Figure 4a: Patient with non healing, arm wound

4a

Figure 2b: Patient showing anterior view of nearly healed medial leg wound after BGWM

2b

Figure 4b: Patient with healed wound after BGWM application

4b

How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers Figure 5a-d Treatment progression with BGWM showing venous ulceration responding to this bioactive matrix

5b

5a

5c

5d

Discussion

given concerns over antimicrobial resistance.

The results of this case series demonstrate the potential efficacy of using a bioactive glass wound matrix (BGWM) for treating chronic venous leg ulcers in an elderly patient population with multiple comorbidities. The ability to achieve complete wound closure in all 6 ulcers after an average of 10 weeks of BGWM application is noteworthy, especially considering the ulcers had been present for an average of 15.1 weeks prior to starting BGWM and were previously non-healing.

Mechanistically, the bioactive glass matrix likely provided the well-vascularized wound bed with a scaffold to facilitate cell migration, attachment, and proliferation of key cell types like fibroblasts and keratinocytes. BGWMs are designed to be gradually remodeled and resorbed as the patient’s own extracellular matrix is deposited.

The mean initial ulcer size of 13.5 cm2 indicates that many of the wounds were quite large, yet the BGWM facilitated healing even for the largest 56 cm2 ulcer. This suggests BGWM may be effective for a range of wound sizes and severity.

Additionally, the short median healing time of 10 weeks compares favorably to expected healing times with standard wound care.

The rapid and significant pain reduction reported by patients is another clinically relevant benefit observed with BGWM use.

Decreasing pain from a mean of 5.8/10 down to 0/10 within just 2-3 dressing changes likely improved patient quality of life and willingness to continue treatment. Chronic wound pain can be challenging to manage.

From a clinical workflow perspective, the ease of BGWM application and ability to use it until full closure without requiring frequent dressing changes is advantageous. The lack of need for systemic antibiotic therapy is also noteworthy

Limitations of this study include the small sample size, lack of a control group, and possible selection bias towards patients felt to be good candidates for BGWM. However, these promising pilot results support further investigation of BGWM in a larger, controlled trial, potentially comparing it to other advanced wound care products. Cost-effectiveness analysis would also be valuable given the expenses associated with chronic wound care.

In conclusion, this case series provides early evidence that a bioactive glass wound matrix may represent an effective tool for treating recalcitrant venous leg ulcers in a complex patient population. The ability to achieve full wound closure, provide rapid pain relief, avoid systemic antibiotics, and streamline dressing changes are all clinically relevant advantages observed. Larger, controlled studies are still needed to better evaluate the safety and efficacy profile of BGWM compared to standard treatments and other advanced wound matrices. But these initial results are promising for this novel wound care approach.

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How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers BGWM is a bioabsorbable wound matrix composed of borate-based glass fibers. Its composition and structural properties have been intentionally engineered to exhibit biocompatibility and facilitate the body’s innate wound healing cascades. Preclinical and clinical evaluations have demonstrated this matrix to be a safe, effective and efficient therapeutic modality for the management of both acute traumatic wounds as well as complex chronic wound etiologies.

The borate-based glass fiber construct provides a conducive three-dimensional scaffold to support the coordinated phases of wound repair. It allows for optimal cellular infiltration, migration, and proliferation of key cell types like fibroblasts, keratinocytes, and endothelial

cells. Concomitantly, the gradual resorption and remodeling of the bioabsorbable matrix facilitates deposition and integration of the patient’s own extracellular matrix proteins.

This biomaterial maintains a physiologically moisture-balanced wound environment conducive to healing. Its inherent flexibility and conformability enable excellent adhesion to the wound bed and periwound area. When applied with appropriate wound bed preparation, the borate glass matrix provides an advanced wound care solution that supports the body’s reparative mechanisms for a diversity of wound presentations across the entire continuum of acute to chronic wound chronicity.

References 1. wcw-admin-support. “What Slows Wound Healing in Older Patients: Effects of Age.” West Coast Wound & Skin Care, 31 July 2022, westcoastwound.com/what-slows-wound-healing-in-older-patients/ 2. Anderson, Kristin, and Rose L. Hamm. “Factors That Impair Wound Healing.” Journal of the American College of Clinical Wound Specialists, vol. 4, no. 4, Dec. 2012, pp. 84–91, https://doi.org/10.1016/j.jccw.2014.03.001.

3. Zemaitis, Michael R, et al. “Peripheral Arterial Disease.” Nih.gov, StatPearls Publishing, 23 May 2023, www.ncbi.nlm.nih.gov/books/NBK430745/ 4. Shi, Chunhu, et al. “Compression Bandages or Stockings versus No Compression for Treating Venous Leg Ulcers.” Cochrane Database of Systematic Reviews, vol. 2021, no. 7, 26 July 2021, https://doi.org/10.1002/14651858.cd013397.pub2 5. National Clinical Guideline Centre (UK). “Barrier Creams.” Nih.gov, National Institute for Health and Care Excellence (UK), Apr. 2014, www.ncbi.nlm.nih.gov/books/NBK333167/ 6. Weyand, Cornelia M., and Jörg J. Goronzy. “Aging of the Immune System. Mechanisms and Therapeutic Targets.” Annals of the American Thoracic Society, vol. 13, no. Supplement_5, Dec. 2016, pp. S422–S428, https://doi.org/10.1513/annalsats.201602-095aw 7. Gould, Lisa, et al. “Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research.” Journal of the American Geriatrics Society, vol. 63, no. 3, Mar. 2015, pp.

427–438, https://doi.org/10.1111/jgs.13332 8. Pickham, David, et al. “Evaluating Optimal Patient-Turning Procedures for Reducing Hospital-Acquired Pressure Ulcers (LS-HAPU): Study Protocol for a Randomized Controlled Trial.” Trials, vol. 17, no. 1, 6 Apr. 2016, https://doi.org/10.1186/s13063-016-1313-5

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9. Milne J, Searle R, Styche T. The characteristics and impact of hard-to-heal wounds: results of a standardized survey. J Wound Care 2020;29:282-288.

10. Armstrong DG, Orgill DP, Galiano RD, et al. A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. Int Wound J. 2022 May;19(4):791-801.

11. Jung S, Day T, Boone T, et al. Anti-biofilm activity of two novel, borate based, bioactive glass wound dressings. Biomed. Glasses 2019; 5:67–75.

12. Rahaman MN, Day DE, Bal BS, et al. Bioactive glass in tissue engineering. Acta Biomater.

2011; 7(6): 2355–2373.

13. Mehrabi T, Mesgar AS, Mohammadi Z. Bioactive Glasses: A Promising Therapeutic Ion Release Strategy for Enhancing Wound Healing. ACS Biomater Sci Eng. 2020;6(10):53995430.

14. Oľga Križanová, et al. “Chronic Venous Insufficiency and Venous Leg Ulcers: Aetiology, on the Pathophysiology‐Based Treatment.” International Wound Journal, 19 Oct. 2023, https:// doi.org/10.1111/iwj.14405.

15. Octavian Andercou, et al. “Radiofrequency Thermal Ablation for the Treatment of Chronic Insufficiency of the Saphenous Vein—a Comparative Retrospective Study.”

International Journal of Environmental Research and Public Health, vol. 20, no. 4, 14 Feb. 2023, pp. 3308–3308, https://doi.org/10.3390/ijerph20043308.

16. Probst, Sebastian. Wound Care Nursing : A Person-Centred Approach. 3rd ed., Amsterdam, Elsevier, 2020.

How to Reduce Treatment Costs for Hardto-Heal Wounds: The Bioactive Glass Wound Matrix Option Editorial Summary Chronic wounds pose significant treatment challenges and financial burdens. Bioactive Glass Wound Matrices (BGWM) have shown promising wound management properties in preclinical and early clinical studies. In this case series, we evaluate the potential cost savings of using BGWM as a treatment for hardto-heal DFUs and VLUs compared to prior failed treatment modalities. The patients with long-standing wounds (3 DFUs, 1 VLU) were treated with BGWM after at least one year of other unsuccessful treatments at a tertiary wound care center. Treatment costs before and during BBBGM therapy were compared. Across the four wounds, the average treatment cost decreased by 60% with the use of BGWM compared to prior advanced modalities. All wounds achieved closure with 4-13 BGWM applications over 7-20 weeks.

C Dr Janale Charlotte Beckford DPM Foot and Podiatric Surgeon Tampa, Florida, United States of America

Dr Palanisamy Rathinasamy MD General Surgeon, Undersea and Hyperbaric Medicine Tampa, Florida United States of America

hronic wounds affect 6.5 million people in the United States, with estimated treatment costs exceeding $25 billion annually.1 Diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) account for a significant portion of this immense clinical and economic burden. About 25% of people with diabetes will develop a foot ulcer in their lifetime, 2 and up to 2% of the adult population suffers from VLUs. 3 These wounds are notoriously challenging to heal, often persisting for months or years despite standard treatments. The associated morbidity, mortality, and treatment costs dramatically impact patient quality of life and rapidly increase healthcare costs. Bioactive Glass Wound Matrix (BGWM) has emerged as a promising therapeutic option for complex wounds. 3-16 BGWM has shown encouraging results in the treatment of DFUs.3 In a prospective, randomized controlled trial, BGWM demonstrated a significantly greater mean wound size reduction compared to standard care in Wagner grade 1 DFUs.3 Given the substantial costs associated with hard-to-heal wounds, there is a pressing need for effective therapies that can reduce the treatment duration and expense. The purpose of this case series is to evaluate the potential cost savings associated with the use of a BGWM in the treatment of chronic DFUs and VLUs that were previously unresponsive to conventional modalities. By comparing the estimated costs before and during therapy, we aim to provide preliminary insights into the economic benefits that this novel matrix may offer in managing these challenging wounds.

Methods Three patients with a total of four chronic

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wounds were treated. The wound types included diabetic foot ulcers (DFUs) (n=3) and a venous leg ulcer (VLU) (n=1). All patients had received standard wound care for at least one year in a tertiary wound care center prior to presentation, with multiple failed treatment modalities. Upon presentation to the wound clinic, the patients were started on a regimen including BGWM. Informed consent was obtained from all participants. Costs prior to BGWM were estimated and compared to costs during BGWM therapy. Estimates were based on top tier pricing for a large integrated delivery network. Costs prior to BGWM comprised of dressings and debridement costs, and not skin graft or cellular and tissue-based product costs, even if those used prior to BGWM. Dressing types included in the estimate were silver alginate and gelling fiber, absorbent dressings, and collagen. Costs during BGWM therapy comprised the matrix and absorbent dressing, plus collagen dressings used between final BGWM application and wound closure. Wound debridement was performed as needed prior to BGWM use, but not after BGWM was initiated; therefore, debridement was not included in BGWM cost estimates. Estimates did not consider hospitalization, antibiotics, or pain medication costs, or reimbursement rates.

Results Patient 1 Clinical Presentation This was a 60-year-old female with two DFUs on the plantar aspect of her left foot present for 8 years without successful closure using numerous advanced therapies shown in Figure 1.

How to Reduce Treatment Costs for Hard-to-Heal Wounds: The Bioactive Glass Wound Matrix Option

“Bioactive Glass Wound Matrix (BGWM) has emerged as a promising therapeutic option for complex wounds." 3-16

Costs

treatment modalities.

The costs calcualted prior to BGWM therapy was $89,568. The costs during BGWM therapy were $18,113, which was an 80% decrease from the cost prior to BGWM.

Results Patient 3 Clinical Presentation

Time to Healing The first DFU closed after 9 BGWM applications over 15 weeks; the second closed after 13 BGWM applications over 20 weeks.

Healing Progression At baseline, the first DFU measured 5.4 cm2 and the second measured 2.7 cm2. After 15 weeks and 9 BGWM applications, the first DFU achieved complete closure. The second DFU closed after 20 weeks with 13 BGWM applications. The estimated pre-BGWM treatment costs were $89,568 over 8 years. The total costs during BGWM therapy were $18,113, representing an 80% cost reduction.

Results Patient 2 Clinical Presentation This patient was a 68-year-old male with a

This patient was a 39-year-old female with a 1-year history of a recalcitrant VLU on her left medial malleolus which had been refractory to other advanced modalities.

Costs The costs prior to BGWM was $10,816. The costs during BGWM therapy was $5,432, a 50% decrease.

Time to Healing The VLU closed after 4 BGWM applications over 11 weeks.

Healing Progression The wound size at baseline was 6.8 cm2.

Following 11 weeks of treatment with 4 BGWM applications, the VLU closed completely.

1.5-year-old DFU on his right heel which was refractory to other treatment modalities shown in Figure 2.

Costs The costs prior to BGWM were $19,080. The costs during BGWM therapy were $9,506, a 50% decrease. After 7 weeks of BGWM therapy with 7 applications, the ulcer achieved complete reepithelialization. The estimated pre-BGWM costs were $19,080, while the BGWM treatment costs totaled $9,506, a 50% decrease.

Time to Healing The DFU closed after 7 BGWM applications over 7 weeks.

Healing Progression The wound measured 4.1 cm2 upon presentation and had failed to close despite multiple

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How to Reduce Treatment Costs for Hard-to-Heal Wounds: The Bioactive Glass Wound Matrix Option

“Given the substantial costs associated with hard-to-heal wounds, there is a pressing need for effective therapies that can reduce the treatment duration and expense. The purpose of this case series is to evaluate the potential cost savings associated with the use of a BGWM in the treatment of chronic DFUs and VLUs that were previously unresponsive to conventional modalities.”

Figure 1: Patient 1 60-year-old female with two DFUs on the plantar aspect of her left foot present for 8 years.

Progress before, after and during BGWM shown.

Figure 2: Patient 2 showing a 68 year old male with a recalcitrant DFU of the right heel present for 1.5 years showing progress before, during and after treatment with BGWM.

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How to Reduce Treatment Costs for Hard-to-Heal Wounds: The Bioactive Glass Wound Matrix Option

“By facilitating healing of hard-to-heal wounds, BGWM reduced costs compared to prior treatment modalities. Patients reported reduced pain and improved quality of life during BGWM therapy. This case series demonstrates the potential for substantial cost savings when using a borate-based bioactive glass matrix in the treatment of hard-to-heal DFUs and VLUs.”

Table 1:

In aggregate, the average cost savings across the four wounds treated with BGWM was 60% compared to prior failed treatment modalities. The mean time to closure was 13.3 +/- 5.4 weeks, with an average of 8.3 +/3.9 BGWM applications required. Patients reported decreased pain and enhanced quality of life during the course of BGWM therapy. No adverse events or complications were noted.

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How to Reduce Treatment Costs for Hard-to-Heal Wounds: The Bioactive Glass Wound Matrix Option

“The exclusion of cellular tissue products and skin grafts from the cost analysis may underestimate the true expense of prior failed treatments. Despite these limitations, the substantial cost reductions and positive clinical outcomes observed across multiple wound types suggest that the BGWM merits further investigation as a cost-effective treatment for refractory DFUs and VLUs.”

Discussion By facilitating healing of hard-to-heal wounds, BGWM reduced costs compared to prior treatment modalities as shown in Table 1.

Patients reported reduced pain and improved quality of life during BGWM therapy. This case series demonstrates the potential for substantial cost savings when using a borate-based bioactive glass matrix in the treatment of hardto-heal DFUs and VLUs. The BGWM resulted in a mean cost reduction of 60% compared to prior unsuccessful treatment modalities. The ability of this novel matrix to facilitate healing in wounds that had persisted for several months to years despite standard care is particularly noteworthy.

By providing a comprehensive wound healing solution, the BGWM may decrease the need for multiple adjunctive therapies and prolonged treatment courses.

Furthermore, the elimination of debridement procedures during BGWM therapy contributes to cost savings. This reduction in debridement frequency not only decreases procedural costs but also minimizes patient discomfort and the risk of debridement-related complications.

The positive impact of the BGWM on patient quality of life should not be overlooked.

Chronic wounds are associated with significant pain, mobility limitations, and psychosocial distress. 12 By facilitating wound closure, the BGWM may alleviate these burdens and improve patient well-being. The reported decrease in pain and enhanced quality of life during BGWM treatment in this case series underscores the potential holistic benefits of this therapy. In this case series, the use of a borate-based bioactive glass matrix resulted in a 60% average cost reduction compared to prior failed therapies in the treatment of hard-to-heal DFUs and VLUs. The BGWM facilitated wound closure, reduced the need for debridement, and improved patient-reported outcomes. These findings highlight the potential economic and clinical benefits of this

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novel matrix for managing challenging chronic wounds. Future controlled studies with larger patient populations are necessary to validate these preliminary results and to further define the role of BGWM in cost-effective wound care algorithms.

Conclusion The limitations of this study include its retrospective nature, small sample size, and lack of a randomized control group. The cost estimates were based on maximum allowable reimbursement rates within a specific healthcare system and may not be generalizable to all settings. Additionally, the exclusion of cellular tissue products and skin grafts from the cost analysis may underestimate the true expense of prior failed treatments. Despite these limitations, the substantial cost reductions and positive clinical outcomes observed across multiple wound types suggest that the BGWM merits further investigation as a cost-effective treatment for refractory DFUs and VLUs..

How to Reduce Treatment Costs for Hard-to-Heal Wounds: The Bioactive Glass Wound Matrix Option

“By providing a comprehensive wound healing solution, BGWM may decrease the need for multiple adjunctive therapies and prolonged treatment courses.”

References 1. Nussbaum SR, Carter MJ, Fife CE, DaVanzo J, Haught M, and Cartwright D. An Economic evaluation of the impact, cost, and medicare policy implications of chronic non-healing wounds. Value in Health, 21(1) 2.Armstrong DG, Boulton AJM,Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017;376(24):2367-2375.

3. Armstrong DG, Orgill DP, Galiano RD, et al. A multi‐centre, single‐blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. Int Wound J. 2022;19(4):791-801.

4. Jung S, Day T, Boone T, Buziak B, Omar A. Anti-biofilm activity of two novel, borate based, bioactive glass wound dressings. Biomed Glas. 2019;5(1):67-75.

5.Rahaman MN, Day DE, Sonny Bal B, et al. Bioactive glass in tissue engineering. Acta Biomater. 2011;7(6):2355-2373.

6. Sen CK. Human wounds and its burden: An updated compendium of estimates. Adv Wound Care (New Rochelle). 2019;8(2):39-48.

Martinengo L, Olsson M, Bajpai R, et al. Prevalence of chronic wounds in the general population: Systematic review and meta-analysis of observational studies. Ann Epidemiol. 2019;29:8-15.

7. Hench LL. The story of Bioglass®. J Mater Sci Mater Med. 2006;17(11):967 8. Rahaman MN, Day DE, Bal BS, et al. Bioactive glass in tissue engineering.

Acta Biomater. 2011;7(6):2355-2373.

9. Jung SB. Borate based bioactive glass scaffolds for hard and soft tissue engineering. In: Advances in Bioceramics and Porous Ceramics VI. John Wiley & Sons, Inc.; 2013:1-19.

10. Ottomeyer M, Mohammadkah A, Day D, Westenberg DJ. Broad-spectrum antibacterial characteristics of four novel borate-based bioactive glasses. Adv Microbiol. 2016;06(10):776-787.

11. Wray P. ‘Cotton candy’ that heals? Borate glass nanofibers look promising.

Am Ceram Soc Bull. 2011;90(4):25-29.

12. Olsson M, Järbrink K, Divakar U, et al. The humanistic and economic burden of chronic wounds: A systematic review. Wound Repair Regen.

2019;27(1):114-125.*Mirragen® Advanced Wound Matrix, ETS Wound Care, Rolla, Missouri 13.Castillo-Garcia E, Thuy Nguyen P. Complex Refractory Wounds: How to Overcome Treatment Recalcitrance and Restore the Healing Trajectory Using Innovative Bioactive Glass. Wound Masterclass. Volume 3. March 2024.

14.Johnson ML, Armstrong DG, Ortega W. How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers in Geriatric Patients with Multiple Comorbidities? Wound Masterclass. Volume 3. March 2024.

15. Laurentin LA, Buck DW, Rivera D. Can Bioactive Glass Matrix be Used to Facilitate Pain Reduction and Healing for Patients with Pyoderma Gangerosum Ulcers? Wound Masterclass. Volume 3. March 2024.

16. Jung S, Schultz G, Mafiz AI, Bevels E, Jaskula K, Brownell K, Lantz E, Strickland A. Antimicrobial effects of a borate-based bioactive glass wound matrix on wound-relevant pathogens. J Wound Care. 2023 Dec 7;32(12):763. https://doi.org/10.12968/jowc.2023.32.12.763

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MasterSeries 60 Minutes Interactive January 24th: 1pm EST | 6pm GMT

Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro Moderator

Global expert Co-chairperson

Global expert Co-chairperson

Global expert

Global expert

Global expert

Miss Negin Shamsian

Dr Monika Gloviczki

Dr M. Mark Melin

Dr Lee Ruotsi

Dr Peter Gloviczki

Dr Abigail Chaffin

Consultant Plastic & Reconstructive Surgeon (Locum)

Scientist and Artist at Vascular Science & Art

Medical Director of the M Health Wound Healing Institute

Medical Director at the Saratoga Hospital Center for Wound Healing and Hyperbaric Medicine

Editor-in-Chief of the Journal of Vascular Surgery Publications.

Professor of Surgery (Emeritus), Mayo Clinic, Rochester, Minnesota

Plastic and Reconstructive Surgeon at Tulane University Medical Director, MedCentris Wound Healing Institute at Tulane

London, United Kingdom

Scottsdale AZ, United States

Mineapolis MN, United States

Saratoga Springs NY, United States

Scottsdale AZ, United States

New Orleans LA, United States

MasterSeries 60 Minutes Interactive Concise. Interactive. Accredited.

Held: January 24th: 1pm EST | 6pm GMT

Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro

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MasterSeries 60 Minutes Interactive Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro

Moderator Miss Negin Shamsian Consultant Plastic and Reconstructive Surgeon (Locum) London, United Kingdom

member Dr M. Mark Melin, Medical Director of the M Health Wound Healing Institute; Dr Lee Ruotsi, Medical Director at the Saratoga Hospital Centre for Wound Healing and Hyperbaric Medicine; Dr Peter Gloviczki, Editor-in-chief of the Journal of Vascular Surgery and Professor of Surgery (Emeritus) at the Mayo Clinic Rochester, Minnesota, and Dr Monika

Introduction

Gloviczki, scientist and artist at Vascular Science and

W

Art. ounds to

progress

inflammatory,

from

hemostasis

proliferative,

and

remodelling phases, but wounds are

Global expert

generally considered hard-to-heal if they are stalled in the inflammation phase and have not entered the

Dr Abigail Chaffin

proliferation phase after 4 weeks of standard of care

Associate Professor of Surgery and Medical Director, MedCentris Wound Healing Institute at Tulane University

therapy.

New Orleans LA, United States

Venous Leg Ulcers (VLUs) account for up to 80% of the 2.5 million leg ulcer cases per year, with an increased

Reconstructive Considerations

incidence in an ever-increasing elderly population;

Supported by

aside from the associated reduced quality of life, the

In the 4 weeks of standard of care, there should be

costs involved with this are substantial, involving a

a 50% reduction in the wound size. If not, it may

high frequency of hospitalizations, wound clinic visits,

be necessary to signal for a change or additional

home healthcare, decreased work capacity, and job

therapies or advanced extracellular matrices (ECM).

loss or time lost from work; in the United States, these

This is important, because generally wound area

costs amount to nearly $15 billion annually.

reduction after 4 weeks is predictive of complete wound healing by 24 weeks. Local and national

MasterSeries: Getting the Best Patient Outcomes

guidelines should be followed, with incorporation of

in Chronic Venous Disease; From Micro to Macro

evidence-based modalities that lead to the highest

includes a panel of global experts including Dr

quality outcomes with the most appropriate resource

Abigail Chaffin, Associate Professor of Surgery and

utilization in an integrated approach.

Medical Director of the MedCentris Wound Healing Institute

106

at

Tulane

Wound Masterclass - Vol 2 - March 2023

University;

editorial

board

The goals are to alleviate pain, rapidly heal the ulcer

© Copyright. Wound Masterclass. 2024

MasterSeries 60 Minute Interactive: Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro

“Humans are designed to live with hypochlorous acid in their tissue, which explains the lack of cytotoxicity of the pure hypochlorous acid (pHA) based cleanser.”

and to prevent long term sequelae.

preservative has a higher therapeutic index compared to the hypochlorite present in Dakin’s, and also

General treatment algorithms for VLUs include

some cleansers that combine variable proportions

commencing

leg

of elements of hypochlorous acid (harmless) and

bed

hypochlorite (toxic). The pH of 3.5 to 5.5 of pHA is well

preparation with a sharp excisional debridement,

below the pKa of HOCl (7.5), with the added attribute

a high consideration for bacterial control with

that the pHA preserved cleanser has a greater efficacy

appropriate wound cleansers (it is possible to use a

with a lower toxicity to the tissue.

elevation,

with

and

standard

then

a

compression,

thorough

wound

pure hypochlorous acid preserved wound cleanser); early use of ECMs when appropriate for coverage of

The hypochlorous acid molecule, a naturally evolving

vital structures, dermal regeneration and accelerating

substance inside the human tissue, forms part of

primary healing of small VLUs (preferred option would

the cellular barrier immunity. Humans are designed

be to use an ovine forestomach matrix graft). Split

to live with hypochlorous acid in their tissue, which

Thickness Skin Grafts (STSG) should be considered for

explains the lack of cytotoxicity of the pHA based

definitive coverage of larger VLUs.

cleanser.

Pure Hypochlorous Acid (pHA) Preserved Cleanser

A study in an academic centre looking at sulfamylon or mafenide and bacterial adherent aggregates reports

This is a pure Hypochlorous Acid (pHA) preserved

that the mafenide solution had a flat curve; very little

cleanser (Vashe®, Urgo Medical North America,

effects occurred on the bacterial adherent aggregates,

Fort Worth, TX), manufactured at 300 ppm (parts

as compared to the pHA based cleanser solution.

per million); it has a pH range of 3.5 - 5.5, which is

Antibiotic Stewardship is a key topic to incorporate

conducive to healing. It is not cytotoxic, unlike

into clinical practice and It is vital not to overuse

standard sodium hypochlorite solutions, which are

antibiotics to prevent the ever evolving challenge of

considered toxic even at low concentrations. This

drug resistance. Mafenide was also unable to remove

product is consumed by organic matter in the wound

Candida colonies, while the pHA preserved cleanser

and dissipates in seconds, so it is safe to use with

did so easily; which also illustrates that while the pHA

ECMs in the same setting.4 For wounds that have

preserved cleanser is able to kill planktonic germs in

microbial adherent aggregates, 5-8 minutes of wound

seconds in a situation where microbial aggregates

contact with the solution should be considered,5 in

adherent to tissue is involved, it may be appropriate

combination with sharp debridement. This mechanical

to soak the wound for 5 - 8 minutes.

2

3

disruption of germs and associated necrotic debris is a rapid process, and does not require long exposure

Ovine (Sheep) Forestomach Matrix

like other some other modalities may.

An effective advanced ECM for use in VLUs is Some evidence and very recent consensus documents

ovine

and guidelines suggest discontinuation of cytotoxic

Antimicrobial; Endoform

cleansing agents such as Dakin’s or solutions that

Aroa Biosurgery, Auckland, New Zealand). After years

contain cytotoxic agents such as chlorhexidine

of research, the forestomach of sheep in New Zealand

gluconate. In 2022 consensus guidelines were

was identified as an ideal starting tissue to construct

published by the International Wound Infection

advanced ECM technologies for soft tissue repair.

Institute,6 which included discussions from global

This source tissue from juvenile sheep (less than 12

experts on the use of hypochlorous acid versus

months of age) is highly abundant in New Zealand,

sodium hypochlorite. A key section of this guideline

and the animals are disease free. The forestomach,

discusses the issue of margin of safety; this is

even from these young animals, is very large, meaning

the therapeutic index.

large sheets of ECM can be easily manufactured. The

© Copyright. Wound Masterclass. 2024

7

Hypochlorous acid as a

forestomach

matrix TM

(OFM)

(EndoformTM

Natural; Myriad MatrixTM,

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MasterSeries 60 Minute Interactive: Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro

“Decellularized extracellular matrix–based biomaterials are of great clinical utility in soft tissue repair applications due to their regenerative properties. ”

forestomach is a highly vascular tissue, designed for digestion that is integral for rapid nutrient absorption.

Utilizing Synergistic Effects of Both Modalities

This also means that residual vascular channels in the graft help it to revascularize more quickly, and

An ideal operative algorithm for STSGs could be

then this tissue undergoes more rapid remodelling,

considered as the following: a combination of

where soft tissues are continuously renewed in

performing a thorough intra-operative ultrasonic

the body; it has a high concentration of secondary

debridement with pure hypochlorous acid solutions;

macromolecules, which are known to be important

sharp debridement with a curette; and ovine

for healing.

forestomach matrix coverage. The graft can then be

12

stapled or sutured in place with a thrombin sealant.

A study of ovine forestomach matrix usage in a military

A standard dressing protocol can be used which

veteran hospital in 201713 shows that in nine months,

can include: a non-adherent silver silicone dressing

cellular or tissue-based graft unit usage decreased by

with Negative Pressure Wound Therapy (NPWT);

60%; expenditures on these grafts decreased by 66%,

appropriate 4 or 5 layer compression wrap dressings,

with a higher and faster rate of healing.

and then immobilization at the ankle or knee as indicated. The most complex patients are often

Chronic wounds tend to be deficient in a quality

admitted, put on bed rest, and some require a stay

ECM; this is comprised of a complex process of cells,

for optimal take of the graft; and compression and

blood vessels, and macromolecules.

post-operative patient education.

10

The ECM is

important for structural and biochemical support.

Chronic wounds often have deficient ECM, senescent fibroblasts and increased matrix metalloproteinases (MMPs). Enhancing and optimising the ECM with a

Global expert

replacement ECM to heal these ulcers more effectively

Dr M. Mark Melin

should be considered. To that end, it is important to

Medical Director of the M Health Wound Healing Institute

consider what features make an ideal replacement?

An ideal advanced ECM affords a rapid 100% or near

Mineapolis MN, United States

100% wound closure, long term tissue durability, cost effectiveness, and an ease of storage and transport.

The Typical Venous Leg Ulcer Checklist

The outcomes that are measured by multiple studies include the percentage of closed wounds, the time

It is important to run a typical VLU checklist like

to closure, wound recurrence or infections, need for

an airplane pilot’s pre-flight checks to maximize

amputation or hospitalization, and a time to return

outcomes and achieve consistency in terms of

to baseline Activities of Daily Living (ADLs), pain

treatment. To begin, a vital check is to make sure

reduction, odour and exudate reduction, and also

that there is adequate blood flow; in current

other adverse effects.

demographics, about 20-25% of patients have some component of either diabetes or a metabolic

Patients that have failed healing of large venous ulcers

syndrome which can compromise both microvascular

with standard of care in conjunction with a granulated

as well as macrovascular arterial flow. Investigation

wound base, with no bone or tendon exposure and a

with venous competency ultrasound is critical in

high quality of skin coverage is desired, a STSG may

identifying both saphenous and non-saphenous

be considered.

reflux and perforator status. The EVRA study and the ESCAR study suggest that axial and non-axial venous reflux should be treated early, managing the venous hypertension as a basis for wound healing.

To attempt healing without managing the venous

108

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MasterSeries 60 Minute Interactive: Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro

“It is prudent to consider biopsy; concerning atypical vs typical ulcerations, if an atypical is missed such as a malignancy, or pyoderma gangrenosum, and it is treated as a typical venous leg ulcer, there will not be a good outcome.”

hypertension is not found to be effective practice.

be a good outcome.

A nutrition evaluation typically falls way down on

Evidence shows that the wound pH should be

the checklist; it is established that the micronutrient

controlled at a mildly acidic, low pH range of

components to maximize nitric oxide production

between 3 to 6. It is established through peer

which improves lymphatic function, micro arterial

reviewed, validated data that decreasing wound pH

vasodilation, venous tone and immune function are

can help with decreasing pathogen proliferation,

all incredibly beneficial to these patients who often

improving angiogenesis, and improving accelerated

times may be micronutrient deficient. It is vital to

epithelialization, when with other types of adjunctive

focus on the B vitamins (B12, B6 folate), and high

modalities.

dose vitamin C to help with decreasing reactive oxygen species and antioxidants; a caveat on vitamin

Another important consideration is compression,

C is that if the patient has a history of renal stones, it

which is critical; it is important to get certified

may be necessary to be careful and discuss with the

lymphedema therapists involved and begin utilizing

primary care physician. Vitamin D can also have an

inelastic Velcro; this is easy to get on and off over

impact, not just on bone health, but on microvascular

the top of dressings, and it is important not to

perfusion. Arginine certainly contributes to nitric

forget about both the foot component and the calf

oxide production and micronized purified flavonoid

component.

fractions (MPFFs). A new way to look at albumin is not necessarily as a marker of overall nutritional

Cost effective wound bed modulation, as shown

health; it is actually a component of the endothelial

with ovine forestomach, should be opted for. Also,

glycocalyx, it helps as a permeability layer, so when

smoking has to be ceased, including vaping.

the albumin is low increased levels of microvascular hyperpermeability may be seen, which can influence

For bacteria proliferation management, a pHA

subcutaneous

compromising

preserved cleanser is recommended; it has a

microvascular arterial perfusion, as well as immune

stable shelf life of approximately 18 months, a pH

function.

range over its shelf life at 3.5 to 5.5, and it is non-

edema,

potentially

cytotoxic for wound and peri-wound environments; Certainly, looking at the medication list is important,

it decreases inhibitory wound bed pathogens; it can

because medications like amlodipine or other

be used in conjunction with NPWT after surgical

calcium channel blockers can contribute directly to

debridement to maximize lowering of the wound

lower extremity edema; typically amlodipine needs

pH, and avoid recurrence of formation of adherent

to be stopped to maximize edema control. Oncology

germ aggregations; it is applicable to all wound sites.

patients undertaking chemotherapy, or who are on

It has been used in trauma, pyoderma wounds, and

hydroxyurea, are certainly at a high risk of inhibited

diabetic foot ulcerations. In terms of the extracellular

long term healing.

matrix, ovine forestomach matrix should be used in the operating room, and Endoform™ Antimicrobial or

Good hyperglycaemic control is important; again,

Endoform™ Natural in the clinic. Myriad Morcells™

hyperglycaemia can shed the very fragile layer of

is another option that is available; it is a structured

the endothelial glycocalyx, which can result in more

retention of architecture from the forestomach of

edema.

young sheep, typically less than 12 months old. The stomach of sheep has to heal very quickly to maintain

It is prudent to consider biopsy; concerning atypical

the health of the animal, so the ovine forestomach

vs typical ulcerations, if an atypical is missed such

matrix has a diverse array of collagens including 1, 2,

as a malignancy, or pyoderma gangrenosum, and it

3, and 5; as well as an abundance of glycoproteins and

is treated as a typical venous leg ulcer, there will not

proteoglycans. All of these are preserved through a

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MasterSeries 60 Minute Interactive: Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro

“The critical catalyst for Buerger’s disease is cigarette smoking; in a patient who is not a cigarette smoker, a diagnosis of this disease cannot be made.”

very specific process and retention of vascular

and skin changes such as hemosiderosis (extravasated

channels, and it is cost effective.

red blood cells in the breakdown of haemoglobin).

Chronic inflammation and fibrosis of skin can often be

It is an important consideration to try to focus

mistaken for cellulitis. The morphology of VLUs tends

on decreasing interstitial edema, and maximizing

to be irregularly shaped, full thickness ulcerations with

lymphatic functionality, also resulting in immune

moderate to large exudate, with typically no exposed

function

underlying bone, tendon, or other structures.

enhancement,

as

by

decreasing

subcutaneous edema we can maximize microvascular arterial perfusion at the 5-micron level. To consider

General

peri-wound lymphatic stasis, it is occurring in almost

workup; ensuring an adequate arterial workup,

treatment

guidelines

include

vascular

every wound; the epiboly we see in wounds is actually

including ankle brachial indices and toe brachial

built-up lymphatic stasis, and when lymphatics are

indices to support that gold standard of multi-layer

static, the immune system does not function well. By

compression. It is important to remember that both

maximizing peri-wound lymphatic stasis resolution,

clinically applied compression and the post-closure

overall wound healing can be improved.11,14,15

garments that the patients wear at home have to be tailored to the patient’s life status. Utilizing

To conclude, the steps should include the checklist

arteriograms, Computed Tomography Angiography

for VLUs with special attention to avoiding missing

(CTA) and Magnetic Resonance Arteriography (MRA).

the identification of Peripheral Arterial Disease (PAD).

It has been observed a growing demographic with

Lymphedema

diabetes and metabolic syndrome in the population.

outpatient wound centers commonly presenting

is

a

common

presentation

to

Another focus point is avoiding undertreating

with open wounds with a multitude of challenges.

lymphedema; recognising malnutrition and treating it

Most outpatient wound centres are poorly equipped

appropriately, not just the protein component but the

to manage lymphedema, and many lymphedema

micronutrients component. In terms of investigations

providers and clinics are unwilling to accept patients

venous ultrasounds must be done early. Vigilance

with open wounds. Therefore, this brings about a

with medications contributing to lower extremity

dilemma that these lymphoedematous wounds need

edema and modify them. Help patients to wean

to be closed before the lymphedema can actually be

themselves off tobacco.

managed appropriately, with the skill and technique that can really only be provided by lymphedema therapists.

Global expert Dr Lee Ruotsi

Arterial Insufficiency Ulceration

Medical Director at the Saratoga Hospital Center for Wound Healing and Hyperbaric Medicine

In this condition the clinical features tend to be

Saratoga NY, United States

the wound was created with a drill-bit. They tend to

punched out, with well-defined edges almost as though occur over distal bony prominences; in appearance,

The Differential Diagnosis of Lower Extremity Ulcerations

the wound beds tend to have an unhealthy and pale granulation tissue. They tend to be fairly dry, with minimal exudate, black to brown eschars, and the

110

VLUs begin distally with the feet and ankles, moving

surrounding skin tends to be ruborous and hairless.

proximally as venous hypertension develops. Over

In terms of management of arterial insufficiency

time varicosities develop, and this is worse after

ulceration, it is vital to make the diagnosis and

prolonged standing or activity and the venous

then refer to an appropriate vascular surgeon.

hypertension symptoms such as aching, discomfort

It is important that there is an adequate arterial

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MasterSeries 60 Minute Interactive: Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro

“Biopsy early and biopsy often; there are very few wounds that can be negatively affected with a 5mm punch biopsy.”

supply. Priorities should be completing the VLU

but getting these wounds to epithelialize is very

checklist; thinking out of the box and ensuring that

difficult.

you make that diagnosis of arterial insufficiency in a timely fashion. Don’t always rely on your fingers;

Pyoderma Gangrenosum

remember to use a hand-held doppler, MRA, and CTA. These are painful ulcers of varying depth and size, with cautiously,

purulent wound beds and a blue-black wound edge.

especially in the ischemic limb; and on the advice

PG is most commonly associated with underlying

from the National Pressure Injury advisory panel: it is

autoimmune and occasionally malignant disease.

important not to debride dry stable heal eschar; leave

The most common association is with inflammatory

it alone allowing it to demarcate.

bowel disease such as ulcerative colitis or Crohn’s

Debridement

should

be

performed

disease. System corticosteroids and other disease modifying agents such as cyclosporin are often

Thromboangiitis Obliterans

used in treatment. A very important concept with Also known as Buerger’s disease, this is an arterial

pyoderma gangrenosum is that of pathergy where, if

clotting in the hands and feet, with the resultant

the ulcers are sharply debrided, they grow large.

ulceration and gangrene. It is a vaso-occlusive, inflammatory vasculopathy, where inflammatory

Marjolin’s Ulcer

thrombi occlude vessels but spare the vessel walls.

The critical catalyst for Buerger’s disease is cigarette

This is an unusual form of squamous cell, or

smoking; in a patient who is not a cigarette smoker, a

occasionally basal cell carcinoma. Marjolin’s ulcers

diagnosis of this disease cannot be made.

were originally described by French surgeon JeanNicholas Marjolin in the late 1700’s, as a squamous cell cancer arising in an area of prior skin trauma. In

Vasculitis

the United States, these are colloquially called scar Vasculitis can occur in any organ system, however

carcinomas or burn carcinomas, and are now known

interestingly the skin is the most common organ

to be roughly 80% squamous cell and 20% basal

system affected. The bilateral lower legs are the most

cell. A 73-year-old lady presented to the clinic with

common location. The typical description is a painful

a large VLU in an area where she had prior venous

palpable purpura. Biopsy is done for diagnosis; doing

leg ulceration. It appeared as a fairly typical looking

a biopsy on the most immature of the areas will lead

venous ulcer. She was quite mobility impaired,

to the highest return in diagnosis. Leukocytoclastic of

so home nursing care was arranged and she was

inflammatory vasculitis is the most common form of

brought back in 4 weeks for a follow-up. When she

cutaneous vasculitis.

returned she had an odd looking area in the superior aspect of the wound; this was biopsied and it turned

Scleroderma

out to be a poorly differentiated squamous cell carcinoma. This patient’s prior area of skin damage C.R.E.S.T.

ended up being her recurrent VLU; biopsy early and

syndrome, and also sometimes known as progressive

biopsy often; there are very few wounds that can be

system sclerosis, is an autoimmune disorder of

negatively affected with a 5mm punch biopsy.

Scleroderma,

most

commonly

the

unknown etiology ulcers, usually over the digits, pre-tibial area, and bony prominences. One of the most troubling features of this disease process if the subcutaneous calcification, known as calcinosis cutis.

There are yellow areas around the periphery of these wounds, so sometimes those areas are able to be distracted or extracted, almost like dental extractions, © Copyright. Wound Masterclass. 2024

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111

MasterSeries 60 Minute Interactive: Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro Diabetic Foot Ulcer

Treat reflux early; vascular specialists should be consulted as soon as possible because we want to

5 year mortality of neuropathic Diabetic Foot Ulcer

treat the underlying incompetence (whether it is

(DFU) is almost 50%. Vascular assessment is of critical

superficial or perforated) early.32

importance. Remember the tri-neuropathy; we always think of the sensory neuropathy, but remember that

Treat iliofemoral venous obstruction; if the patient

we have the motor neuropathy that leads to the bony

has associated deep venous obstruction, we certainly

deformities, and then the autonomic neuropathy that

need to do this. This can be done very effectively with

leads to the dry foot, leading to fissuring and cracking.

relatively low risk but good clinical success.

Infection and osteomyelitis are common.

For persistent/ recurrent ulcers, treat residual reflux Global expert Dr Peter Gloviczki Editor-in-Chief of the Journal of Vascular Surgery Publications.Professor of Surgery (Emeritus), Mayo Clinic, Rochester, Minnesota Scottsdale AZ, United States

or obstruction. If stenting is not possible, the Palma procedure or surgical bypass should be performed.

For nonhealing wound ulcers, duplex scanning should be repeated to look for new or recurrent reflux; the effectiveness here of skin grafting and bilayer cellular therapy is well evidenced. To summarize, the best strategy to treat venous ulcers is to confirm the right diagnosis, optimize the local care, treat the infection, initiate compression therapy, and treat the underlying

Interventions for Treatment of Chronic Venous Insufficiency

reflux and obstruction early to prevent/ treat, if there is ulcer recurrence.

Chronic venous disease is a huge spectrum of medical

Global expert

conditions. This is one of the most prevalent medical conditions in the world. With the increasing age of the population, there is likely to be a higher prevalence of venous ulcerations, and the associated economic cost of this is well understood. Although it affects

Dr Monika Gloviczki Scientist and Artist at Vascular Science and Art Scottsdale AZ, United States

elderly patients more frequently, there is a significant economic burden because of loss of working days in

Scientific Societies' Guidelines

people who are still working, and it is not infrequent to see these patients having to retire early, with a

The last guidelines of the American Venous Forum

reduced quality of life.1,26

and Society for Vascular Surgery suggest nutrition assessment in any patient with VLU and evidence of

There are guidelines on how to treat patients. These

malnutrition; nutritional supplementation should be

guidelines need upgrades frequently, not only

provided if malnutrition is identified. For long standing

because there is a large number of new venous

or large venous ulcers, the 2 societies recommended

ulcer treatments that are not interventional, but

adjunctive therapy with pentoxifylline or Micronized

because there have been tremendous changes in

Purified Flavonoid Fraction (MPFF).

vascular reconstruction because of the endovascular revolution.27,28,29,30

The guidelines of the Wound Healing Society attributed recommendations of Level I for pentoxifylline and

Strategy for VLU

MPFF, in conjunction with compression therapy to improve healing of venous ulcers.

In establishing the diagnosis of venous ulcers,

112

duplex scanning is extremely important to establish

Just recently the ESVS published Clinical Guidelines

the status of venous incompetence, and excluding

on the management of Chronic Venous Disease and

the underlying arterial disease is important, as is

included adjuvant pharmacotherapy to the algorithm

performing the VLU checklist, looking at diabetes

of treatment of patients with active venous ulcers. In

vasculitis and other rare ulcerations. Compression

the recommended pharmacologic treatments, based

treatment is of course a usual part of immediate

on the level A evidence, the guidelines listed MPFF,

treatment, and treatment of infection is extremely

hydroxyethylrutosides, pentoxifylline or sulodexide,

important. Cleanse and debride the ulcer and

combined with compression and local wound care.

apply dressing. Maintain a moist surface, absorb

All the guidelines were using the same definition of

and excess fluid, and protect the surrounding skin.

scientific evidence, levels A, B, and C.

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MasterSeries 60 Minute Interactive: Getting the Best Patient Outcomes in Chronic Venous Disease; From Micro to Macro Scientific Evidence for Nutritional Pharmacologic Treatment in VLU

and

The cost-effectiveness analysis showed that MPFF adjuvant therapy improved the cost-effectiveness ratio by 45%. For Pentoxifylline the Cochrane

Nutrition

systematic review concluded that it is an effective adjunct to compression bandaging for treating VLUs

Published January 2023, a systematic review on

and may be effective in the absence of compression.

nutrition stated that VLU patients tend to have a

The whole group of flavonoids was also an object of

deficit of nutrients such as vit A, D, or zinc and an

the Cochrane review for VLUs treatment. It included

excess of lipids and carbohydrates. A clinical trial with

MPFF and hydroxyethylrutosides and was inconclusive

an oral nutritional supplement found that high calorie,

in despite of significant ulcer healing improvement

high protein, enriched oral supplementation had a

documented, as some trials were considered to be

positive effect on ulcer healing. Another systematic

poorly reported. The sulodexide’s Cochrane review

review concluded that omega-3 fatty acids, Mg, zinc,

concluded that it may increase the healing of VLUs,

vit A, C, D and resveratrol with probiotics improved

however the evidence was judged to be of low quality.

VLU healing.

In conclusion, nutritional supplements are indicated Pharmacologic compounds

for patients with vitamin/ mineral deficiencies. For venous leg ulcers, in addition to standard wound care

As for pharmacologic treatment, the scientific

and compression therapy, an adjunctive treatment

evidence available for MPFF is a meta-analysis

with MPFF, pentoxifylline, hydroxyethylrutosides and

including 5 RCTs. This meta-analysis demonstrated

sulodexide was established in several RCTs, meta-

a significantly better healing rate in the MPFF group

analysis and Cochrane’s systematic reviews.

and shorter median time to healing: 16 weeks for MPFF vs 21 in the control group.

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29. Gloviczki P, Lawrence PF, Wasan SM, Meissner MH, Almeida J, Brown KR, Bush RL, Di Iorio M, Fish J, Fukaya E, Gloviczki ML, Hingorani A, Jayaraj A, Kolluri R, Murad MH, Obi AT, Ozsvath KJ, Singh MJ, Vayuvegula S, Welch HJ. The 2022 Society for Vascular Surgery, American Venous Forum, and American Vein and Lymphatic Society clinical practice guidelines for the management of varicose veins of the lower extremities.

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30. Raffetto JD, Ligi D, Maniscalco R, Khalil RA, Mannello F. Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment. J Clin Med. 2020 Dec 24;10(1):29. doi: 10.3390/jcm10010029. PMID: 33374372; PMCID: PMC7795034.

31. Goldschmidt E, Schafer K, Lurie F. A systematic review on the treatment of nonhealing venous ulcers following successful elimination of superficial venous reflux. J Vasc Surg Venous Lymphat Disord. 2021 Jul;9(4):1071-1076.e1. doi: 10.1016/j. jvsv.2020.12.085. Epub 2021 Feb 26. PMID: 33647527.

32. Gohel MS, Heatly F, Liu X et al. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med 2018; 378:2105-114 DOI: 10.1056/NEJMoa1801214 33. Gloviczki P, Bergan JJ, Rhodes JM, Canton LG, Harmsen S, Ilstrup DM. Mid-term results of endoscopic perforator vein interruption for chronic venous insufficiency: lessons learned from the North American subfascial endoscopic perforator surgery registry. The North American Study Group. J Vasc Surg. 1999 Mar;29(3):489-502. doi: 10.1016/s0741-5214(99)70278-8. PMID: 10069914.

34. Köksoy C, Bahçecioğlu İB, Çetinkaya ÖA, Akkoca M. Iliocaval outflow obstruction in patients with venous ulcers in a small comparison study between patients with primary varicose veins and chronic deep vein disease. J Vasc Surg Venous Lymphat Disord. 2021 May;9(3):703-711. doi: 10.1016/j.jvsv.2020.08.019. Epub 2020 Aug 19.

PMID: 32827736.

35. Lawrence PF, Hager ES, Harlander-Locke MP, Pace N, Jayaraj A, Yohann A, Kalbaugh C, Marston W, Kabnick L, Saqib N, Pouliot S, Piccolo C, Kiguchi M, Peralta S, Motaganahalli R. Treatment of superficial and perforator reflux and deep venous stenosis improves healing of chronic venous leg ulcers. J Vasc Surg Venous Lymphat Disord. 2020 Jul;8(4):601-609. doi: 10.1016/j.jvsv.2019.09.016. Epub 2020 Feb 21.

PMID: 32089497.

36. Marston W, Ta ng J, Kirsner RS, Ennis W. Wound Healing Society 2015 update on guidelines for venous ulcers. Wound Repair Regen. 2016 Jan- Feb;24(1):136-44. doi: 10.1111/wrr.12394. PMID: 26663616.

37. De Maeseneer MG, Kakkos SK, Aherne T, Baekgaard N, Black S, Blomgren L, Giannoukas A, Gohel M, de Graaf R, Hamel-Desnos C, Jawien A, JaworuckaKaczorowska A, Lattimer CR, Mosti G, Noppeney T, van Rijn MJ, Stansby G, Esvs Guidelines Committee, Kolh P, Bastos Goncalves F, Chakfé N, Coscas R, de Borst GJ, Dias NV, Hinchliffe RJ, Koncar IB, Lindholt JS, Trimarchi S, Tulamo R, Twine CP, Vermassen F, Wanhainen A, Document Reviewers, Björck M, Labropoulos N, Lurie F, Mansilha A, Nyamekye IK, Ramirez Ortega M, Ulloa JH, Urbanek T, van Rij AM, Vuylsteke ME. Editor’s Choice - European Society for Vascular Surgery (ESVS) 2022 Clinical Practice Guidelines on the Management of Chronic Venous Disease of the Lower Limbs. Eur J Vasc Endovasc Surg. 2022 Feb;63(2):184-267. doi: 10.1016/j. ejvs.2021.12.024. Epub 2022 Jan 11. Erratum in: Eur J Vasc Endovasc Surg. 2022 AugSep;64(2-3):284-285. PMID: 35027279.

38. García-Rodríguez MT, Rodríguez-Parrado M, Seijo-Bestilleiro R, González-Martín C. Influence of Nutrition Status and Compression Therapy on Venous Ulcer Healing: A Systematic Review. Adv Skin Wound Care. 2023 Jan 1;36(1):45-53. doi: 10.1097/01.

ASW.0000902492.97059.f2. PMID: 36537775.

39. Melo PG, Mota JF, Nunes CAB, Malaquias SG, Coelho ASG, Soriano JV, Bachion MM. Effects of Oral Nutritional Supplementation on Patients with Venous Ulcers: A Clinical Trial. J Clin Med. 2022 Sep 26;11(19):5683. doi: 10.3390/jcm11195683. PMID: 36233551; PMCID: PMC9570985.

40. de Souza T, Monteiro JDC, Curioni CC, Cople-Rodrigues C, Citelli M. Nutrients with Antioxidant Properties and Their Effects on Lower-Limb Ulcers: A Systematic Review. Int J Low Extrem Wounds. 2022 Jan 24:15347346221074861. doi: 10.1177/15347346221074861. Epub ahead of print. PMID: 35072533.

41. Coleridge-Smith P, Lok C, Ramelet AA. Venous leg ulcer: a metaanalysis of adjunctive therapy with micronized purified flavonoid fraction. Eur J Vasc Endovasc Surg. 2005 Aug;30(2):198-208. doi: 10.1016/j.ejvs.2005.04.017. PMID: 15936227.

42. Simka, M., Majewski, E. The Social and Economic Burden of Venous Leg Ulcers.

Am J Clin Dermatol 4, 573–581 (2003). https://doi.org/10.2165/00128071-20030408000007 43. Jull AB, Arroll B, Parag V, Waters J. Pentoxifylline for treating venous leg ulcers.

Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD001733. doi: 10.1002/14651858.

CD001733.pub3. PMID: 23235582; PMCID: PMC7061323.

44. Wu B, Lu J, Yang M, Xu T. Sulodexide for treating venous leg ulcers. Cochrane Database Syst Rev. 2016 Jun 2;2016(6):CD010694. doi: 10.1002/14651858.CD010694. pub2. PMID: 27251175; PMCID: PMC9308373.

45. Scallon C, Bell-Syer SE, Aziz Z. Flavonoids for treating venous leg ulcers. Cochrane Database Syst Rev. 2013 May 31;(5):CD006477. doi: 10.1002/14651858.CD006477. pub2. PMID: 23728661.

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Join global wound care experts to answer all your questions about Surgical Site Infection (SSI)

MasterSeries 60 Minutes Interactive Concise. Interactive. Accredited.

December 13th: 1pm EST | 6pm GMT

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Supported by

MasterSeries 60 Minutes Interactive Surgical Site Infection (SSI): All Your Questions Answered

Moderator Miss Negin Shamsian Consultant Plastic and Reconstructive Surgeon (Locum) London, United Kingdom

This is a really important topic and for this MasterSeries on SSI we have an esteemed global panel, including: Dr Jonathan Johnson, the founder and surgical director of the comprehensive wound care service in Washington DC; Dr Mark Melin, the Medical Director

Introduction

of the M Health Wound Healing Institute in Fairview,

S

Minnesota, United States; Dr Hüseyin Kemal Raşa, the urgical site infection (SSI) presents a real

European president of the Surgical Infections Society;

challenge for healthcare systems across the

Dr Windy Cole, Director of Wound Care Research, Kent

world, but they also have a substantial impact

State University of Podiatric Medicine; and Dr Michael

on patients. Statistics have shown that about 60% of

Magro consultant obstetrician and gynaecologist in

these surgical site infections are actually completely

London.

preventable; despite that, the rates are still high. Each patient undergoing a surgical procedure has a 5%

Global expert

chance of developing an SSI, which is a considerable

Dr Jonathan Johnson

number.

Surgical Director, Comprehensive Wound Care Services

Relating to SSI, NHS costs are between £10,000 and

Washington DC, United States

£100,000 per patient, and it is also associated with extended hospital stays, delays in going back to work

Supported by

and returning to normal life for the patient.

Initial Management of the Surgical Infection

On another note, SSI is caused by bacteria/

Being a surgeon and working on wounds for multiple

microorganisms that get into the body through the

years, I can say one of the most important aspects we

incisions that we make in surgery, and treating them

look at as far as SSI’s are concerned is making sure

involves use of antibiotics. This has contributed a lot

that:

to the spread of antibiotic resistance, particularly in low and middle income countries; about 11% of

•

We adequately close the wound

•

We make sure we have a post-op review of the

patients in these countries are infected, and in Africa as a whole, one in five women who have a cesarean section end up having an SSI.

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MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI)

“You must have great communication with your patient, so they understand that this is a team-based approach; pre-operative instructions are a vital part of controlling and minimizing SSI’s.”

If the patient needs antibiotics, start them on

What is your Go-To Surgical Prep?

antibiotics and if you do see any signs and symptoms of SSI; erythema in duration, active purulent drainage,

Prepping the wound depends on whether the

etc., you have to treat it very aggressively.

patient has acute or increased colonization or critical colonization, as it is required to remove the biofilm

A post-op surgical review and post-op surgical follow-

as much as possible for a clean wound bed, prior to

up is key; with an outpatient patient we want to make

grafting or any type of surgical debridement. If there

sure they come back within at least three to five days

is increased colonization at the site, then it must

for a review.

be removed, depending on what is available and the patient’s body and how it reacts. It’s important

What Do You Do Pre-Operatively to Minimize the

to remove the biofilm as much as possible; we use

Risk of SSI?

a device which looks at the fluorescence of the wound, at the increased amount of bio-burden and

Firstly, you must have great communication with your

the increase in the amount of bacteria at the wound

patient, so they understand that this is a team-based

site prior to debriding, but then also after debriding

approach; pre-operative instructions are a vital part

to make sure we removed as much of it as possible;

of controlling and minimizing SSI’s. Another important

it’s a specific protocol that depends specifically on the

thing to make sure they are taking their pre-operative

patient.

antibiotics, and they make sure that they are adequately cleaning the area prior to surgery and not

How Do You Identify SSI Early in Your Patients, In

scrubbing the skin. After that, everything should work

Person and Remotely?

in an active process; firstly, prep the patient in the operating room and explain all education issues prior

Telehealth has newly emerged within the last couple

to surgery; secondly, in the operating room or at the

of years due to the pandemic; it’s a great tool to use

bedside before starting the procedure, we need to

for surveillance but also to monitor our patients. The

have a timeout and make sure that everyone involved

number one thing to look for or to tell the patient or

understands what their role is, like prep of the area,

patient’s caregiver, is to look for:

explaining to the patient what is going on and what the procedure is, making a clean line incision, and

•

Redness or erythema around the wound site

•

Induration/ thickness or hardness around the

making sure throughout the process to extensively close everything. Another important thing is to make

wound site

sure there is adequate post-op dressing on the scar.

Before making the incisions, its important to note

•

Active purulent drainage or decolourization coming from the wound site

who is at a higher risk for developing SSI, and patients with diabetes, problems with coagulopathy, ischemic problems, or comorbidities are at higher risk. In

•

Warmth or pain at the wound site

addition, patients who have had surgeries near the site of the current surgery or the same surgical

If the surgical site has sutures or staples that are

incision are at a higher risk, as sometimes patients

intact, this could contribute to the wound being

have adverse effects in the same area. Patients with

infected, causing pain or erythema; its best to seek

autoimmune issues and nutritional defects need

medical attention as quickly as possible.

to be adequately prepped prior to performing the procedure.

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MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI)

“Patients that may not present the typical signs and symptoms are patients with comorbidities and patients with darker skin tones.”

What Group of Patients May Not Present Typical

to your patient; is there increased pain? Is there

Symptoms?

increased temperature at the wound site?

Patients with autoimmune issues, diabetes, and

We want to look at whether there are foreign bodies

extensive comorbidities may not show active signs

at the wound site; does the patient have staples, does

and symptoms of infections acutely, compared

the patient have sutures; are there implants at the

to patients that do not have these comorbidities.

site?

It’s very important to make sure patients with are

We want to make sure we can decrease the infection

diabetic, that you’re regularly checking on the wound,

as quickly as possible and to make sure that the

discussing any issues with changes of the skin, and

patient improves quickly. Another issue we should

any of the previously mentioned signs or symptoms.

look at is whether the patient is post-op, and if they

One of the other major things that we need to focus

have active drainage; for example, if they have active

on is patients that have darker skin tones, and this

drainage from a total hip or a total knee arthroplasty,

goes back to a lot of research and looking at the

then we should put a dressing over the top of the site

bacterial burden and fluorescence at the wound site

to see if we can decrease the amount of infection

in patients that have darker skin. If we look at what we

actively and topically before you start the antibiotics.

call the Fitzpatrick scale, we have FP1 all through all

Sometimes in long-term care if the patient does have

the way through to FP6; typically patients that are FP1

active infection and drainage from the wound site we

are fair skinned and they typically burn and tan, and

will use a silver alginate dressing or a product that has

then we have patients that are FP6; typically darker

a silver component.

comorbidities,

specifically

in

patients

that

skinned and they don’t burn or tan, but the signs and symptoms of erythema in duration, pain and changes

Are There Any Adjuncts To Clinical Skills That You

in the skin warmth and temperature may not be

Use As An Initial Point Of Investigation?

apparent in these patients. Typically these are your patients that are FP4, FP5, and FP6.

We typically focus on utilizing bacterial fluorescence technology, but there is a role for culturing the

We did a study utilizing bacterial fluorescent imaging

wound and obviously biopsying of the wound, if the

because with this device we can see the increased

wound is not progressing after you’ve initiated the

amount of that bacterial burden and fluorescence

standard of care management; we do utilize these if

in the patients that may not have what we call

the wound continues to decline after we’ve used POA

active clinical signs and symptoms through simple

antibiotics, or after we’ve used topical antibiotics, but

observation.

typically that is what we call a ‘game time decision’, or a ‘wound time decision’ (if I may put this into the

So, this group of patients that may not present

lexicon) because it just depends on how the patient

the typical signs and symptoms are patients with

reacts postoperatively; if you do need to utilize the

comorbidities and patients with darker skin tones.

culture or the biopsy it is an option available to us, but if not, what we should focus on is standard of care.

How Do You Do An Initial Management Of Somebody With An SSI? One thing we do first of all is to observe the wound; take a look at the wound, determine the amount of erythema, determine the amount of induration; determine the amount of active purulent or abnormal colour of exudate at the wound site. Observe, talk

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MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI)

“The idea of wound hygiene has been taking hold in the wound care space, so we should consider wound hygiene post-operatively, too. Currently, most hospitals are not doing a good job with treating post-operative sites to prevent biofilm formation.”

Global expert Dr Windy Cole Director of Wound Care Research, Kent State University of Podiatric Medicine

•

Practicing aseptic techniques

•

Screening our patients; making certain that we understand our patients, their comorbidities, and their underlying conditions

Streetsboro OH, United States

The Role of Biofilm Biofilm is a colony of polymicrobials; multiple organisms, bacteria, fungus, yeast, etc., that form on the wound surface. Planktonic bacteria are free floating bacteria that will implant on the surface of a wound or a surgical incision and then they start to connect with one another. They do something we call quorum sensing; they start to share information.

They may share DNA or RNA; they could share antibiotic resistance, and they start to mutate, and begin to secrete a kind of extra polymeric substance.

This substance forms a micro-dome that protects the biofilm. Interestingly, the organisms within a biofilm are not affected by oral and IV antibiotics and some topical antibiotics or antimicrobials have difficulty penetrating through the biofilm construct because of this extra polymeric substance, so these wounds initially are not necessarily infected, but they are contaminated with surface bacteria. The number of complexities of the microbes that are involved in this biofilm on the surface increases the patient’s risk of developing a wound infection. We also know that the presence of biofilm will cause inflammation, and cause wounds to be chronic, so if we have biofilms that are in the area of a surgical incision, and we allow them to develop, if we don’t treat them appropriately

•

Surveillance; closely monitoring our patients, especially post-operatively

•

Practicing antibiotic stewardship

Associated SSI must not be neglected; this is the main cause of most hospital acquired infections, and the development of SSI is typically due to the microbial contamination of the surgical site. This is either from endogenous or exogenous sources, although most commonly it is the endogenous with superficial site infection, but they can go into deeper tissues. This causes severe patient outcomes with the infection affecting underlying organisms, organs, and then leading to more surgical procedures that are necessary and long term, amputations.

The idea of wound hygiene has been taking hold in the wound care space, so we should consider wound hygiene post-operatively, too. Currently, most hospitals are not doing a good job with treating postoperative sites to prevent biofilm formation.

Choosing the appropriate dressing is vital; we potentially manage, control, and remove the exudate from the incision site. There are newer bandages that have entered the market which also have

we can get an SSI.

antimicrobial properties that can assist in wound

We can also get inflammation that continues, and

reforming, and help to control any kind of SSI.

these wounds won’t heal; this becomes a particularly problematic situation for a lot of our patients postoperatively, so we all must practice strategies to prevent infection and SSI. Some of the strategies that

hygiene, hopefully prevent biofilm bacteria from

Antimicrobial stewardship is very important as the world is facing a crisis because we have a rising rate of bacterial resistance, due to our overuse of antibiotic

are most commonly known in practice are these six:

agents. The bacterial resistance is directly related to

•

Hygiene; washing our hands frequently

care doctors will be prescribed antibiotics, and the

•

Environmental hygiene; cleaning our spaces

unnecessary. Prior treatment with commonly used

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overuse; most patients when they go to their primary statistics say that 90% of antibiotics prescriptions are antibiotics actually increases the risk of infection in

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MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI)

“To emphasize prevention, one of the least talked about components with preoperative management of patients is nutrition.”

patients, which also increases the risk of morbidity,

temperature management is critical. Telehealth

hospital stays, and an overall increase in health care

management has its place because we can fit patients

costs and mortality. So, we must practice better

in if they’re concerned about their incisions, but it can

antimicrobial stewardship which helps support better

also complicate making a diagnosis. I would encourage

clinical care, outcomes and lowers healthcare costs.

everybody that if there’s ever a question which makes you suspect SSI in a Telehealth interview, bring the

The first step we must follow is to avoid antibiotics

patient in for a physical examination and bring that

when they’re not indicated, which means wound

patient in soon.

infection should be diagnosed clinically, and there must be signs and symptoms of infection. Just because

For signs and symptoms, we’ve all been taught in

there is a wound, and they’re mostly colonized, this

our medical training to listen to the patient, ask the

does not indicate the need to prescribe antibiotics,

patient the symptoms; do they have fevers, chills?

although antimicrobials, surface topical agents,

Are there cognitive changes? Sometimes getting a

dressings, might be useful in some of these patients,

history from a family member can be very important,

we’re going to prescribe the appropriate regimen to

and when we’re looking at the wound we’re looking

narrow a spectrum for the likely bacteria present.

for redness, increasing pain, increasing drainage, or

Culture results are important to treat the most

change in the drainage.

common or frequent pathogens, as it is unnecessary to treat low virulence bacteria, and antibiotics should

In accurately identifying SSI, we have to be aware of

be used for the correct duration, just long enough

the atypicals. In the immunosupressed patient, the

to achieve symptom resolution. Patients should be

elderly, or those with cognitive disorders, SSI may

treated with topical therapy and usually for about

present in a relatively atypical fashion; having a high

one to two weeks maximum for soft tissue infection,

degree of suspicion is so important as clinicians.

and six weeks for bone infection. Choosing the agent that shows the least risk and best outcomes to avoid

Nutrition

adverse reactions to patients is important.

To emphasize prevention, one of the least talked There are many antimicrobial agents out there,

about components with pre-operative management

for example; silver products, hypochlorous acid

of patients is nutrition. I think albumin has gotten

solutions, surfactant agents that are antimicrobial,

a little bit of a bad reputation in terms of being a

and many new innovative dressings on the market.

marker for nutrition, and it may actually not be as good a marker for nutrition, as it’s a more important

Global expert Dr M. Mark Melin Medical Director of the M Health Wound Healing Institute Mineapolis MN, United States

marker for degree of vascular hyperpermeability.

The albumin is a significant component of something called the endothelial glycocalyx. It helps with permeability, much like Gore-Tex within a rain jacket.

As a constituent of the endothelial glcocalyx, when albumin is low there’s increased miscrovascular hyperpermeabilty which results in increased tissue

Top Tips for Identifying Surgical Infection

edema,

which

can

compromise

microvascular

arterial perfusion at the five micron level, where all

126

Early identification of suspected SSI is critical;

oxygen and nutrient delivery truly occurs. I think we

this is going to be based upon pre-operative risk

need to start thinking about albumin not as a true

factor assessment, interoperative factors, such as

marker of nutrition but as a marker of endothelial

length of procedure, complications, transfusions,

cell health, and helping ultimately with oxygen

and of course perioperative and interoperative body

nutrient delivery, indirectly, to the incisions that

Wound Masterclass - Vol 2 - March 2023

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MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI)

“Our SSI rate reduced by 45% when comparing a six-month period in using Leukomed® Sorbact®, to the same period previously using the old dressings.”

we’re making in our patients and expect to heal. Also,

Global expert

consider control of perioperative hyperglycemia;

Dr Michael Magro

almost counter-intuitively, preoperative carbohydrate

Consultant Obstetrician and Gynaecologist

loading in patients can actually help with post-

London, United Kingdom

operative hyperglycemia management. This has been recognised in multiple surgical guidelines, and I would counsel you to seek out those guidelines and talk to your nutritionist within the hospital about preoperative carbohydrate loading, which is now a very validated method for assisting in glycemic control perioperatively. The other important thing to focus on is micronutrients; within our wound clinic, we routinely use micronutrients, in addition to standard of care with protein, and the micronutrients we are using are all focusing on endothelial cell function. Vitamin D has an important role of emphasising microvascular functionality. In Minnesota we have a lot of vitamin D deficiency, and it’s not unusual for us to be using 3,000 - 5,000 international units of vitamin D on a daily basis.

Vitamin C at 1000mg can help decrease inflammation, which will certainly help improve microvascular perfusion; vitamin B12, B6 and methylfolate can all be part of a methylenetetrahydrofolate reductase pathway

that’s

connected

with

homocysteine

ultimately resulting in recoupling endothelial nitric oxide synthase to maximise nitric oxide production which

results

in

vasodilation,

lymphangion

contractility, as well as immune functionality. Vitamin A, for patients who have recently been on steroids, helps with collagen production. Micronized Purified Flavonoids Fractions (MPFF) such as diosmin and hesperidin have also been shown to be a significant component in improving microvascular health; they are inflammation quenching, decreasing ICAM-1 and VCAM-1; they improve venous function and lymphangion functionality.

Strategies for Reducing Post-Cesarean Section Infections The National Institute for Clinical Excellence (NICE) produced guidelines in 2021 using randomized controlled trials (RCT) data which show that after cesarean section, if we used a dressed called Leukomed® Sorbact® we could reduce SSI’s and as a consequence of that, also save money. Leukomed® Sorbact® is a bacteria binding, sterile wound dressing.

It can be applied for up to seven days, and not only does it act as a barrier for infection, it ‘sucks’ the bacteria away from the wound and traps it in the dressing so that the bacteria load at the surgical site is less. It is also waterproof, meaning that patients can shower with it on.

We have had a very good success story at the Barking, Havering and Redbridge University Hospitals in reducing SSI after cesarean section (CS), using Leukomed® Sorbact® dressings.

For us, the dressings were roughly £10 per person, and our previous dressings were much cheaper at £1 per person, so we wanted to see if we used a much more expensive wound dressing whether it would make a difference for us over time, and whether it would be a worthwhile investment.

Our SSI rate reduced by 45% when comparing a six-

Conclusion

month period in using Leukomed® Sorbact®, to the

As professionals we really have to choose counsel

the women that were readmitted, we reduced the

wisely and appropriately, and choose the correct time and pre-operative intervention such as compression, edema reduction, and nutrition maximization to result in decreased and minimized post-operative complication risk.

© Copyright. Wound Masterclass. 2024

same period previously using the old dressings. For days spent in hospital by 61%. Antibiotic prescriptions for women with post-cesarean SSI were reduced by 36%.

We had great improvements and are really pleased with these results, and this is something we will be

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MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI)

“We were able to save nearly £140,000, even with the additional cost of the wound dressings.”

continuing long term.

Guidelines

In terms of cost savings, when we looked at the

There are many SSI prevention guidelines including

number of SSIs that we had reduced in a six-month

those from the American College of Surgeons (ACS)

period, and considering the average costs involved

- 2016, the World Health Organization (WHO) - 2016,

with SSIs, we were able to save nearly £140,000, even

modified in 2018 because of the hyperbaric oxygen

with the additional cost of the wound dressings. It is

recommendation, and the Centers for Disease

important to note that this excludes the savings from

Control and Prevention (CDC) - 2017.

reduced antibiotic prescription, so the real figure will be even higher.

I accept that these guidelines can be tiresome, but I have no doubt that with them we can prevent half

Conclusion

of all SSI’s. There are strong consensuses across the guidelines, as well as some conflicts.

There is a lot of scepticism when companies approach you with their product. I had the same attitude, which

To summarise the strongest agreements between

is why we didn’t implement this just based on the

guidelines, we have five recommendations:

NICE guidelines, and we kept this audit data. We were very clear that if SSI rates didn’t improve in the six-

•

Parenteral antimicrobial prophylaxis; this is the most significant recommendation in all these

month period, and save us money, we would go back

three guidelines

to the old dressing.

•

Alcohol-based skin preparation

I would urge clinicians to try this, even if it is just in

•

Perioperative glycemic control

a similar six-month period, and see if your SSI rates

•

Temperature regulation to normothermia

improve. It is a very simple thing to do, and at worst

•

Maintenance of normal tissue oxygenation

you will only spend a little more money.

The remaining recommendations did not achieve Global expert Dr Hüseyin Kemal Raşa Surgical Infections Society, European President Kocaeli, Turkey

unanimous agreement across these three guidelines.

There are however strong considerations, such as smoking cessation, decolonization;

colorectal

screening and surgery

bundles,

perioperative surgical attire; operating room traffic control, operating room disinfection, and use of the WHO perioperative checklist. These have become

Implementation of Guidelines

cornerstones of SSI prevention.

When we compare SSI rates in developed countries

To summarise some of the conflicts and controversies

to low and middle income countries, there is a huge

when it comes to SSI prevention, they include:

difference; in low and middle income countries SSI

128

is the most surveyed and most frequent type of

•

Preoperative chlorhexidine gluconate bathing

infection, and incidence rates range from 1.2 and 23.6

•

Local antibiotics

per 100 surgical procedures, with a pooled incidence

•

Surgical wound irrigation

of 11.8%. If we consider the clinical outcomes of SSI,

•

Antiseptic drapes

it leads to significant morbidity and mortality, and

•

Antiseptic-impregnated sutures

extended hospital stays. Patients who develop SSI

•

Advanced dressings

have a 2 to 11 fold higher risk of death; 75% of deaths

•

Wound protectors

in patients with SSI are directly attributable to the SSI.

•

Prophylactic negative pressure wound therapy

Wound Masterclass - Vol 2 - March 2023

© Copyright. Wound Masterclass. 2024

MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI)

“I believe most of these controversies will be cleared up over the next few years, and we will have a clearer consensus.”

I believe most of these controversies will be cleared

How and when will feedback be given to the target

up over the next few years, and we will have a clearer

audience and managers? How can patients also be

consensus.

informed?

I am very proud to be part of the team that, in

Sell it: Reminders and communications

2018, published the WHO implementation manual, designed to bring this dogmatic knowledge in the

How are you promoting an intervention to ensure

guidelines to the clinician and to the bedside.

that there are cues to action at the point of care and messages are reinforced to health workers and

We have an Inter-Process Communication (IPC)

patients?

multimodal improvement strategy which involves five categories:

Do you have capacity/ funding to develop promotional messages and materials?

Build it: Training and education Live it: Culture change What type of training should be used to ensure that the intervention will be implemented in line with

Is there demonstrable support for the intervention

evidence-based policies and how frequently?

at every level of the health system? For example, do senior managers provide funding for equipment and

Does the facility have trainers, training aids, and the

other resources? Are they willing to be the champions

necessary equipment?

and role models for IPC improvement?

Teach it: System change

Are teams involved in co-developing or adapting the intervention? Are they empowered, and do they feel

What

infrastructures,

equipment,

supplies

and

ownership and the need for accountability?

other resources (including human) are required to

Take Home Messages

implement the intervention?

Does the physical environment influence health

The prioritisation of feasible but high-impact pilots,

worker

such as SSI in intensive care units, will be a good place

behaviour?

How

can

ergonomics

and

human factor approaches facilitate adoption of the

to start.

intervention?

Slowly scaling-up, in a stepwise manner, and moving Are certain types of health workers needed to

from paper to electronic forms is a good trick.

implement the intervention?

The mainstay of these strategies is multidisciplinary Check it: Monitoring and feedback

collaboration, and mentorship, such as yearly surveillance seminars, site support visits to assess

How can you identify the gaps in IPC practices or other

case findings, and denominator data.

indicators in your setting to allow you to prioritize your intervention?

The integration of HAI and AMR surveillance efforts including a multidisciplinary working group and

How can you be sure that the intervention is being

a master trained in surveillance that can provide

implemented correctly and safely, including at the

leadership is also an important concept.

bedside? For example, are there methods in place to observe or track practices?

© Copyright. Wound Masterclass. 2024

We definitely need careful consideration of definitions

Wound Masterclass - Vol 2 - March 2023

129

MasterSeries 60 Minute Interactive: Surgical Site Infection (SSI) before use; this is critical. We need to discuss factors

In almost all success stories we have incorporated

such as the use of validated standards, consistency

an evaluation strategy to monitor performance and

and feasibility of data collection. We must use the

provide feedback to frontline staff. Monitoring and

same terminology and definitions.

feedback can heighten the sense of urgency, promote accountability, and show clinicians how they are

We also need clear procedures for data management

performing.

and promotion of data for action.

See all Wound Masterclass MasterSeries on demand: bigmarker.com/wound-masterclass

References 1. Aslam MS, Ahmad MS, Riaz H, Raza SA, Hussain S, Qureshi OS, et al. Role of Flavonoids as Wound Healing Agent. Phytochemicals - Source of Antioxidants and Role in Disease Prevention [Internet]. 2018 Nov 7; Available from: http://dx.doi. org/10.5772/intechopen.79179 2. Broekhuizen, Lysette Na; Mooij, Hans La; Kastelein, John JPa; Stroes, Erik SGa; Vink, Hansa,c; Nieuwdorp, Maxa,b. Endothelial glycocalyx as potential diagnostic and therapeutic target in cardiovascular disease. Current Opinion in Lipidology 20(1):p 57-62, February 2009. | DOI: 10.1097/MOL.0b013e328321b587 3. Aldecoa, C., Llau, J.V., Nuvials, X. et al. Role of albumin in the preservation of endothelial glycocalyx integrity and the microcirculation: a review. Ann. Intensive Care 10, 85 (2020). https://doi.org/10.1186/s13613-020-00697-1 4. Yuwen, P., Chen, W., Lv, H. et al. Albumin and surgical site infection risk in orthopaedics: a meta-analysis. BMC Surg 17, 7 (2017). https://doi.org/10.1186/ s12893-016-0186-6 5. D. G. Armstrong, J. R. Hanft, V. R. Driver, A. P. S. Smith, J. L. Lazaro-Martinez, A. M. Reyzelman, G. J. Furst, D. J. Vayser, H. L. Cervantes, R. J. Snyder, M. F. Moore, P. E. May, J. L. Nelson, G. E. Baggs, A. C. Voss, on behalf of the Diabetic Foot Nutrition Study Group 6. Chronic Wound Care Management and Research 2015:2 129-136. International Journal of Cell Biology, Volume 2015, Article ID 701738 7. Summers S, Yakkanti R, Ocksrider J, Haziza S, Mannino A, Roche M, Hernandez VH. Effects of Venous Insufficiency in Patients Undergoing Primary Total Knee Arthroplasty: An Analysis of 1.2 Million Patients. J Knee Surg. 2021 Aug 31. doi: 10.1055/s-0041-1733901. Epub ahead of print. PMID: 34464986.

8. Carmichael J, Dennis D, Jennings J, Stevens-Lapsley J, Bade M. Feasibility and initial efficacy of a multimodal swelling intervention after total knee arthroplasty: A prospective pilot study with historical controls. Knee. 2022 Mar;35:25-33. doi: 10.1016/j.knee.2022.01.008. Epub 2022 Feb 17. PMID: 35183923.

9. Summers S, Yakkanti R, Haziza S, Vakharia R, Roche MW, Hernandez VH. Nationwide analysis on the impact of peripheral vascular disease following primary total knee arthroplasty: A matched-control analysis. Knee. 2021 Aug;31:158-163. doi: 10.1016/j.knee.2021.06.004. Epub 2021 Jun 29. PMID: 34214955.

10. Singh TP, Velu RB, Quigley F, Golledge J. Association of chronic venous disease with major adverse cardiovascular events. J Vasc Surg Venous Lymphat Disord.

2022 May;10(3):683-688. doi: 10.1016/j.jvsv.2021.08.021. Epub 2021 Sep 8. PMID: 34506962.

11. Patel M, Lee SI, Akyea RK, Grindlay D, Francis N, Levell NJ, Smart P, Kai J, Thomas KS. A systematic review showing the lack of diagnostic criteria and tools developed for lower-limb cellulitis. Br J Dermatol. 2019 Dec;181(6):1156-1165. doi: 10.1111/ bjd.17857. Epub 2019 Jun 28. PMID: 30844076; PMCID: PMC6916392.

12. MacLeod BG, Klarich CS, Wessman LL, Gaddis KJ, Konstantinov NK, Wubben A, Melin MM. Fluorescent Imaging as a Component of Diagnosing Pyoderma Gangrenosum: A Case Report. Adv Skin Wound Care. 2022 Jun 1;35(6):1-6. doi: 10.1097/01.ASW.0000820248.26138.bc. Epub 2022 Mar 29. PMID: 35426849.

13. Ehmann S, Walker KJ, Bailey CM, DesJardins JD. Experimental Simulation Study to Assess Pressure Distribution of Different Compression Applications Applied Over an Innovative Primary Wound Dressing. Wounds. 2020 Dec;32(12):353-363. Epub 2020 Aug 17. PMID: 33370244.

14. Anatone AJ, Shah RP, Jennings EL, Geller JA, Cooper HJ. A risk-stratification algorithm to reduce superficial surgical site complications in primary hip and knee arthroplasty. Arthroplast Today. 2018 Oct 15;4(4):493-498. doi: 10.1016/j. artd.2018.09.004. PMID: 30560182; PMCID: PMC6287286.

15. Kwon J, Staley C, McCullough M, Goss S, Arosemena M, Abai B, Salvatore D, Reiter D, DiMuzio P. A randomized clinical trial evaluating negative pressure therapy to decrease vascular groin incision complications. J Vasc Surg. 2018 Dec;68(6):17441752. doi: 10.1016/j.jvs.2018.05.224. Epub 2018 Aug 17. PMID: 30126781.

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16. Report on the Burden of endemic health care- associated infection worldwide.

Geneva: World Health Organization; 2011 (http://www.who.int/infectionprevention/publications/burden_hcai/en/) 17. Allegranzi B, Bagheri Nejad S, Combescure C, Graafmans W, Attar H, Donaldson L et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta- analysis. Lancet. 2011; 377:228–41 18. Bagheri Nejad S, Allegranzi B, Syed SB, Ellis B, Pittet D. Health care-associated infection in Africa: a systematic review. Bull World Health Organ. 2011; 89:757–65.

19. Monahan M, Jowett S, Pinkney T, Brocklehurst P, Morton DG, Abdali Z, Roberts TE. Surgical site infection and costs in low- and middle-income countries: A systematic review of the economic burden. PLoS One. 2020 Jun 4;15(6):e0232960. doi: 10.1371/ journal.pone.0232960. PMID: 32497086; PMCID: PMC7272045.

20. Liu Y, Xiao W, Wang S, Chan CWH. Evaluating the direct economic burden of health care-associated infections among patients with colorectal cancer surgery in China. Am J Infect Control. 2018 Jan;46(1):34-38. doi: 10.1016/j.ajic.2017.08.003. Epub 2017 Sep 28. PMID: 28967510.

21. Ban KA, Minei JP, Laronga C, et al. American College of Surgeons and Surgical Infection Society surgical site infection guidelines, 2016 update. J Am Coll Surg.

2017;224(1):59-74.

22. Global Guidelines for the Prevention of Surgical Site Infection. WHO; 2018.

23. Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. Centers for Disease Control and Prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 2017;152(8):784-791. doi:10.1001/jamasurg.2017.0904 24. Fields AC, Pradarelli JC, Itani KMF. JAMA. 2020 Mar 17;323(11):1087-1088.

25. Schmitt C, Lacerda RA, Turrini RNT, Padoveze MC. Improving compliance with surgical antibiotic prophylaxis guidelines: A multicenter evaluation. Am J Infect Control. 2017 Oct 1;45(10):1111-1115. doi: 10.1016/j.ajic.2017.05.004. Epub 2017 Jun 16. PMID: 28629754.

26. Allen J, David M, Veerman JL. Systematic review of the cost-effectiveness of preoperative antibiotic prophylaxis in reducing surgical-site infection. BJS Open. 2018 Apr 14;2(3):81-98. doi: 10.1002/bjs5.45. PMID: 29951632; PMCID: PMC5989978.

27. Ho YH, Wang YC, Loh EW, Tam KW. Antiseptic efficacies of waterless hand rub, chlorhexidine scrub, and povidone-iodine scrub in surgical settings: a meta-analysis of randomized controlled trials. J Hosp Infect. 2019 Apr;101(4):370-379. doi: 10.1016/j.jhin.2018.11.012. Epub 2018 Nov 28. PMID: 30500384.

28. Nthumba PM, Stepita-Poenaru E, Poenaru D, Bird P, Allegranzi B, Pittet D, Harbarth S. Cluster-randomized, crossover trial of the efficacy of plain soap and water versus alcohol-based rub for surgical hand preparation in a rural hospital in Kenya. Br J Surg. 2010 Nov;97(11):1621-8. doi: 10.1002/bjs.7213. PMID: 20878941.

29. Mehtar S, Wanyoro A, Ogunsola F, Ameh EA, Nthumba P, Kilpatrick C, Revathi G, Antoniadou A, Giamarelou H, Apisarnthanarak A, Ramatowski JW, Rosenthal VD, Storr J, Osman TS, Solomkin JS. Implementation of surgical site infection surveillance in low- and middle-income countries: A position statement for the International Society for Infectious Diseases. Int J Infect Dis. 2020 Nov;100:123-131. doi: 10.1016/j. ijid.2020.07.021. Epub 2020 Jul 24. PMID: 32712427; PMCID: PMC7378004.

30. Ariyo P, Zayed B, Riese V, Anton B, Latif A, Kilpatrick C, Allegranzi B, Berenholtz S. Implementation strategies to reduce surgical site infections: A systematic review.

Infect Control Hosp Epidemiol. 2019 Mar;40(3):287-300. doi: 10.1017/ice.2018.355.

Epub 2019 Feb 21. PMID: 30786946.

31. Rasa K, Kilpatrick C. Implementation of World Health Organization Guidelines in the Prevention of Surgical Site Infection in Low- and Middle-Income Countries:What We Know and Do Not Know. Surg Infect (Larchmt). 2020 Sep;21(7):592-598. doi: 10.1089/sur.2020.163. Epub 2020 Jun 1. PMID: 32478641.

Sponsored By Essity. All production resources provided by Essity. © Copyright. Wound Masterclass. 2024

Wound Cleaning Products:

Masterclass GUIDES Introduction This Masterclass Guide is a concise overview aimed at exploring the use of Prontosan®. Prontosan® offers a specialized wound care solution comprising a cleansing solution and wound gel. Consider incorporating Prontosan® into your practice guided by individual patient needs and wound characteristics.

What Is Prontosan®?

Prontosan®

Keywords ■ Prontosan ■ Wound Care ■ Prontosan® Solution ■ Prontosan Wound Gel/ Gel X ■ Polyhexanide (PHMB) ®

®

■ Wound Healing ■ Wound Management ■ Ulcers ■ Burns ■ Surgical Wounds

Figure 1:

■ Prontosan® is a comprehensive wound care solution consisting of a cleansing solution and a wound gel, formulated to assist in the management and healing of various types of wounds

■ It comprises two key components: Prontosan® Solution and

Prontosan® Wound Gel/ Gel X. The solution is used for wound irrigation and cleansing, while the gel is applied directly to the wound bed

■ It contains polyhexanide (PHMB), an effective antimicrobial agent

that combats a broad range of microorganisms, including bacteria and fungi. It also contains betaine, which contributes to maintaining a balanced moisture level on the wound’s surface and preventing the reformation of biofilm

■ It is designed to promote wound healing by creating an

How Prontosan® Works? The Ten Step Guide 1.

Select the appropriate patient.

2.

Examine the wound to determine its size, depth, and condition. Note any signs of infection, inflammation, or other abnormalities.

3.

Cleanse the wound using Prontosan Irrigation solution. Gently remove debris, excess exudate, and any foreign particles.

shown to accelerate healing by supporting cell migration and minimizing tissue desiccation

4.

Dry using sterile gauze, avoiding excess rubbing.

■ Prontosan® Wound Gel/ Gel X aids in the removal of necrotic (dead)

5.

Squeeze a small amount of Prontosan® Wound Gel/ Gel X onto a clean, sterile surface. Use a sterile applicator or clean gloves to pick up the gel.

■ It is suitable for various wound types, including surgical wounds,

6.

Apply a thin and even layer of the gel directly to the wound bed.

Ensure complete coverage, especially in deeper wounds.

7.

Gently spread the gel over the wound using a sterile applicator or clean, gloved finger. Avoid applying excessive pressure that could disrupt healing tissue.

8.

Place an appropriate wound dressing over the gel to protect the wound and maintain its moist environment. Ensure the dressing covers the entire wound area and is securely in place.

9.

Record the date, time, and details of the wound care procedure in the patient’s medical records. Include information about the type of dressing used and any observations made during the process.

environment conducive to tissue regeneration, granulation, and angiogenesis (formation of new blood vessels)

■ The antimicrobial action of PHMB in Prontosan® helps prevent and

control infections in wounds, reducing the risk of complications that can hinder the healing process

■ It helps maintain a moist wound environment, which has been

tissue from the wound bed, promoting the growth of healthy tissue and assisting in wound debridement ulcers (such as diabetic, pressure, and venous veg ulcers), burns, and donor sites used for skin grafts

■ The presence of a moist gel on the wound can offer pain relief, particularly in wounds with exposed nerve endings

■ The products are typically easy to apply and integrate into wound care routines, following the guidelines provided by healthcare professionals used for skin grafts

10. Patient Follow-Up: Schedule regular follow-up appointments to assess the progress of wound healing and adjust the treatment plan as necessary.

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Wound Masterclass - Vol 2 - December 2023

Wound Cleaning Products:

Masterclass GUIDES

Prontosan®

What Types of Wounds Are Suitable?

What Types of Wounds Are Not Suitable?

■ Surgical wounds ■ Chronic wounds ■ Pressure ulcers ■ Minor abrasions and cuts ■ Diabetic Foot Ulcers

■ Allergies ■ Implanted Devices ■ Do not use on hyaline cartilage

Figure 2: Prontosan® Wound Gel X

■ Traumatic wounds ■ Burns ■ Venous ulcers ■ Wounds with delayed healing

and in aeseptic joint operations

Adverse Effects: Chronic use may cause irritation.

Figure 3: Prontosan® Wound Gel application

■ Pregnancy and breastfeeding ■ Do not use for infusion or injection ■ Should not be used on the central

nervous system (CNS) or the meninges, in the middle ear or inner ear or in the eyes

Figure 4: Prontosan® Wound Solution

Wound Masterclass - Vol 2 - December 2023

2

Wound Cleaning Products:

Masterclass GUIDES

Prontosan®

What Is the Evidence?

Clinical studies and research papers have explored various aspects of the usage of Prontosan®, including its impact on wound healing, infection prevention, pain relief, and overall wound management. These studies often involve both Prontosan® Solution and Prontosan® Wound Gel.

Efficacy

■ Wound Cleansing: Prontosan®

Solution is effective for wound irrigation and cleansing, removing debris and contaminants. It can help create a clean wound bed, which is essential for optimal healing

■ Infection Prevention: The

antimicrobial properties of Prontosan®, particularly polyhexanide (PHMB), contribute to preventing and controlling wound infections. By reducing microbial load, it supports a healthier wound environment

■ Moist Wound Healing: Prontosan®

products help maintain a moist wound environment, which is known to facilitate wound healing processes such as cell migration, angiogenesis, and granulation tissue formation

■ Debridement: Prontosan® Wound

Infection

■ The antimicrobial properties

of Prontosan®, particularly polyhexanide (PHMB), contribute to preventing and controlling wound infections. By reducing microbial load, it supports a healthier wound environment

■ For wounds that are already

infected, the antimicrobial properties of Prontosan® can help control and manage the infection. By reducing the number of microorganisms, it supports the body’s natural defense mechanisms and provides a healthier environment for healing

Costs

■ Prontosan® solution 40ml ampoule costs around £15 for the box of 24

■ Prontosan® gel 50g tube costs around £12

■ From the date of opening, the solution and gel can be used up to 8 weeks for single patient use (40 ml ampoule, single use only)

■ Long shelf life at ambient temperature storage (3 years after date of manufacture)

■ Prontosan® can also be used

preventively in wounds at risk of infection, such as surgical wounds or wounds with compromised immune function. It helps reduce the likelihood of infection development

Gel’s debridement properties aid in the removal of necrotic tissue, allowing for the growth of healthy tissue and promoting wound healing

■ Pain Relief: The presence of the

moist gel on the wound can provide pain relief, particularly in wounds with exposed nerve endings

Prontosan has tested efficacy on multiple species of bacteria within 60 seconds, this means Prontosan is suitable for irrigation in wounds where only planktonic bacteria is a concern.

For wounds suspected of containing biofilm, irrigation with Prontosan is shown to be more effective than other cleansers over 3 – 6 day periods, however for maximum benefit in wounds where biofilm is a possibility, an enhanced contact time is recommended. The betaine within Prontosan provides the surfactant / cleansing effect for biofilm disruption and cleansing of slough and PHMB is present as an adjuvant ingredient.

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Wound Masterclass - Vol 2 - December 2023

Wound Cleaning Products: Prontosan®

Masterclass GUIDES

Key Points ■ It is a comprehensive wound care solution that includes solution for cleansing and wound gel for direct wound application ■ It contains polyhexanide (PHMB), an antimicrobial agent effective against a range of microorganisms, supporting infection prevention and control

■ It maintains a moist wound environment, promoting tissue regeneration, granulation, and angiogenesis, key processes in wound healing ■ Prontosan® Wound Gel/ Gel X aids in debridement by removing necrotic tissue, while its moist presence on wounds can offer pain relief ■ It is suitable for various wound types, including surgical wounds, ulcers, burns, and donor sites, providing adaptable wound care ■ It’s antimicrobial properties help prevent wound infections by reducing microbial load and disrupting biofilm formation ■ Prontosan® Wound Gel/ Gel X prevents the reformation of biofilm. It acts as an effective barrier to reduce colonisation and to decontaminate the wound bed between dressing changes

There is no limit set for the treatment duration with Prontosan® Wound Irrigation Solution. In clinical trials, the longest documented treatment duration was 6 months. In fact, Prontosan® is especially designed for the long term treatment of hard-to-heal wounds. Prontosan Wound Gel and Wound Gel X should be cleansed off at every dressing change, continual contact should not exceed 30 days, most likely dressing changes occur more regularly than this and usually within 7 days.

References 1.

2.

3.

4.

Prontosan® Wound Gel [Internet]. www.bbraun.com. Available from: https://www.bbraun.com/en/products/b/prontosan-wound-gel.html Prontosan® Wound Irrigation Solution [Internet]. www.bbraun.com. Available from: https://www.bbraun.com/en/products/b/prontosan-wound-irrigation-solution-for-wounds-and-burns.html Guidance: Prontosan Solution and Gel X [Internet]. Available from: https://www.bsuh.nhs.uk/library/wp-content/uploads/sites/8/2020/08/Prontosan-Application-Brighton-and-Sussex-Final.pdf Prontosan (betaine-polyhexanide) dosing, indications, interactions, adverse effects, and more [Internet]. reference.medscape.com. Available from: https://reference.medscape.com/drug/prontosan-betaine-polyhexanide-999621

Useful Links

Use your device to scan this QR code for more information about Prontosan® wound cleaning products

More information

How to Cite this Article Masterclass Guide: Wound Cleaning Products: Prontosan® Wound Masterclass. Volume 2. No 6. December 2023

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Wound Masterclass - Vol 2 - December 2023

4

Masterclass GUIDES Introduction This comprehensive masterclass guide offers an in-depth look at the Mirragen® Bioactive Glass Wound Matrix (BGWM) designed to support wound closure.

Discover insights into the product’s unique composition, mechanisms of action, and clinical applications. Discover suitable wound types for its use, master the proper usage techniques through step-by-step instructions and video, ensuring maximum efficacy and patient comfort. An evidence-based mini case series showcases the transformative power of this cutting-edge wound care solution in real-world clinical settings.

Bioactive Glass Wound Matrix Mirragen®

Keywords ■ Moisture Management ■ Wounds ■ Wound Healing

■ Bioactive glass matrix ■ Wound ■ Wound care

Figure 2: Bioactive Glass: high purity raw materials are mixed and heated at extremely high temperatures

What Is Mirragen® Bioactive Glass Wound Matrix?

■ Mirragen Glass Wound Matrix is a flexible and formable ®

skin substitute that easily adapts to any wound bed. Made from natural elements, the porous fiber and microsphere structure absorbs wound exudate to maintain moisture balance.

■ Solely composed of bioabsorbable fibers and particles. It

is a flexible and moldable wound matrix that can be easily customized to fit the wound bed. The fiber structure of Mirragen® Glass Wound Matrix allows it to absorb fluid from the wound and facilitate natural wound healing.

■ The material is biocompatible and will eventually be fully

absorbed at the wound site. This resorption process is initiated by the exposure of the material to fluid at the wound site.

How to use Mirragen® Glass Wound Matrix Watch Video of Application

■ Mirragen Glass Wound Matrix is sterile and aseptic techniques ®

should be used.

■ Prepare the wound bed using standard wound cleaning and debridement procedures.

Figure 1: Mirragen® Glass Wound Matrix

■ Dry the periwound area.

■ Cut or shape Mirragen Glass Wound Matrix to fit the size of ®

the defect, directly in the wound bed, ensuring full coverage.

■ If applying Mirragen Glass Wound Matrix to a dry wound, moisten ®

the wound bed and/or the material with sterile saline to aid in maintaining a moist wound environment.

■ Use appropriate fixation as determined by wound location, size and depth.

■ Add a non-adherent layer to secure Mirragen Glass Wound ®

Matrix to the wound bed.

■ Place a suitable secondary dressing over the Mirragen Glass ®

Wound Matrix to manage the wound environment and protect the wound area. The secondary dressing should completely cover the Mirragen® matrix.

■ Reapplication of Mirragen and all secondary dressings should be ®

conducted according to standard wound care practices every 3 to 7 days. Heavily exudating wounds may require more frequent dressing changes.

■ As healing occurs, new tissue may grow into Mirragen Bioactive ®

Wound Matrix. This is desirable, DO NOT forcibly remove or debride areas of Mirragen® that are embedded or adhered to the wound site, these are 100% bioabsorbable and will eventually be absorbed at the wound site.

■ Cut or shape Mirragen Advanced Wound Matrix to fit the ®

size of the wound bed. Place the material directly in the wound, ensuring the entire wound bed is covered.

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Wound Masterclass - Vol 3 - March 2024

Bioactive Glass Wound Matrix

Masterclass GUIDES

Mirragen®

When Should I use Mirragen® ?

■ Venous ulcers ■ Pressure ulcers ■ Diabetic ulcers

■ Surgical wounds ■ Wound dehiscence ■ Trauma wounds

■ Calcitrant Wounds ■ Hard-to-Heal Wounds ■ Pyoderma Gangrenosum

■ ■ ■

Atypical wounds Undermined wounds Skin graft donor sites

What are the Clinical Results So Far? Clinical Overview : Mini Case-Series Diabetic Ulcers

Refractory Wounds

Venous Leg Ulcers

Surgical Wounds

Atypical Wounds

A 64-year-old man presented to the wound care clinic with a one year history of a diabetic foot ulcer.

A 62-year-old man presented to the wound care clinic after a lengthy hospital stay due to sepsis.

During his hospital stay, he had an abscess on his lower right leg, which was incised and drained.

A 45-year-old man was admitted following a C5-7 spinal cord contusion, from a offroad dirt bike accident with a delay in primary treatment of over 30 hours.

A 46-year-old woman with Pyoderma Gangrenosum (PG) of the right arm.

The patient had a history of diabetes and neuropathy, delaying wound healing.

A 43-year-old woman presented to the wound care clinic with a chronic lower leg ulcer that had no previous care due to patient neglect in seeking treatment.

Pressure from the motorcycle caused compartment syndrome of the right leg.

The wound was treated for four months with NPWT.

The patient has a history of morbid obesity, hypertension, lymphedema, venous insufficiency, extreme bioburden with mixed bacteria and fungus, producing a malodorous wound.

Having recovered fully from sepsis, the patient was discharged to the wound center.

The wound was unable to undergo debridement because of the pain.

Prior treatments included three surgical closure attempts, two failed skin substitute products and one amnion graft.

The wound bed was initially debrided, removing all necrotic debris and slough.

Mirragen® Bioactive Glass Wound Matrix was applied weekly to the wound bed and affixed using a non-adherent silicone dressing, then wrapped with gauze.

The clinician was extremely impressed with how effective Mirragen® was at providing the right environment to support the body’s ability to heal this wound, particularly after other failed treatments.

The provider found dressing changes were much quicker and simpler compared to other skin substitutes and was impressed with how easy it was to apply Mirragen® to the wound bed.

One further year of treatment with skin substitutes and multiple collagen products.

A plastic surgeon discussed other options including grafts or amputation.

Mirragen® Bioactive Glass Wound Matrix ® was applied to the wound bed at weekly intervals.

The wound was not disturbed on subsequent visits and did not require any additional debridement.

The wound progressed towards closure after only six applications of Mirragen® within 42 days.

The dermatology team instigated steroids, STSG and a skin substitute, without success.

At week 1, the wound measured 8 cm x 8 cm x 2 cm, with a wound surface area of 64 sq cm

At weekly reviews, the patient returned for wound check and reapplication.

Mirragen® was reapplied at each visit and secured in similar fashion.

He underwent decompression surgery of his right leg. He was transferred intense physical rehab and continued wound care. The wound surface area was initially 112 sq cm.

Past medical history included lower limb amputation due to PG. A non-healing wound was present for 6 years.

Two weeks before scheduling the split thickness graft treatment commenced with Mirragen® Bioactive Glass Wound Matrix.

At each visit, the wound was cleansed and debrided. Mirragen® was applied and covered with a non-adherent foam dressing.

The patient also had the following comorbidities, which contributed to delayed healing: diabetes, renal failure on dialysis, stroke, and peripheral vascular disease resulting in amputation.

Initially the complex wound measured 29 cm x 4 cm, 116 sq cm with desiccated necrotic tendon and fascia.

The wound, necrotic tissue and tendon were debrided, and Mirragen® Bioactive Glass Wound Matrix was applied to the wound bed.

Weekly reviews performed and no additional debridement required.

Mirragen® was applied once per week and after 18 weeks of Mirragen®, this complex and hard-to-heal wound is closing.

Measuring 3 cm x 0.5 cm, 1.5 sq cm the wound was noticeably clean and improving at week 18 and mirragen® was discontinued and standard of care was administered until the wound closed.

The provider was satisfied with the support Mirragen® provided to the body’s natural healing process and ease of placement wound bed.

Mirragen® was applied to the wound seven times over a 56 day period.

The wound progressed towards closure with seven applications of Mirragen® over 56 days.

The patient noticed early on that the odor from her wound had decreased significantly after just a couple of applications of Mirragen® and dressing changes were painless and comfortable.

This helped to ensure patient compliance with weekly visits to the clinic.

Mirragen®’s synthetic bioactive porous glass fibers, causes wicking of body fluids, which aids in the placement of the product, and once in the wound bed, mimics a fibrin clot, a well-documented healing process, allowing the body’s natural healing process to proceed.

NPWT was used 3 times a week over exposed tendon with twice daily intensive physical therapy.

Mirragen® was used for tendon coverage and STSG was then performed.

Mirragen® was applied to the wound bed with contact layer and NPWT for 4 days post op.

Conversion to standard dressings occurred

by Week 3 in this challenging wound resulting from acute spinal cord injury and multiple trauma to right lower extremity, due to healing progression.

All wounds, including both donor and skin graft sites, progressed towards closure in 3 weeks with 3 applications of mirragen®.

There was no evidence of scar contraction and there was improvement in the graft.

Mirragen was selected because of its effectiveness at managing the wound environment, while supporting the body’s natural healing process and minimizing the need for multiple weekly dressing. ®

The wound was 8.2cm L x 5 cm W x 0.2 cm D, with a red, odorous, non-granulating, and painful wound bed and high exudate.

The wound was cleansed with normal saline, dried with gauze and Mirragen® was applied to the wound bed, covered with a nonadherent perforated dressing, and steristrips.

After the first two weeks, of Mirragen® the secondary dressing was decreased to one every 5 days, for exudate management.

A superabsorbent dressing with borders was applied.

Wound progressed to closure at 18 weeks with applications of Mirragen® with a significant decrease in pain reported by patient.

The provider was able to clean the wound without pain and dressing changes were significantly faster.

A significant decrease in product use because dressing changes reduced from 4 times a week to once a week.

On the last visit, the provider mentioned that the use of Mirragen® prevented an amputation on this patient.

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Bioactive Glass Wound Matrix

Masterclass GUIDES

Mirragen®

What Is the Evidence?

The potential benefits and evidence supporting the use of Mirragen®, a novel bioactive glass wound matrix (BGWM) in the treatment of chronic, non-healing wounds is set out in the clinical evidence. The data, collected from various published retrospective case series, randomized controlled trials, and economic analyses, highlights the ability of BGWM to improve healing times, reduce costs, and streamline wound care practices.

Time to Healing

Cost Reduction

■ In a randomized 12-week treatment after 2 weeks of

screening, BGWM showed a favorable outcome in the treatment of patients with diabetic foot ulcers compared to standard of care (SOC) treatment.2

■ In a randomized trial of 40 patients receiving SOC or SOC

plus BGWM for 12 weeks, a significantly higher proportion of wounds healed after 12 weeks of BGWM treatment at 70% compared to SOC alone (70% vs. 25%; adjusted P = .006).2

■ In a retrospective case series, five patients with 6 venous

leg ulcers were treated all wounds healed after an average of 10.0 weeks (range: 3-27 weeks) during the use of BGWM, despite being present for an average of 15.1 weeks prior to initial BGWM application.7

■ A prospective pilot study involving three patients with

a total of eight chronic, treatment-resistant pyoderma gangrenosum (PG) ulcers demonstrated that all previously non-healing wounds were returned to a healing trajectory following the introduction of BGWM therapy. 8

■ The application of BGWM resulted in the successful healing of all previously non-healing PG wounds, with patients experiencing significant pain reduction and no adverse events. 8

■ BGWM accelerates wound healing, with a wound closure rate of 6 weeks compared to 17 weeks with standard of care, reducing wound duration by 336 days. 2

■ In another case review, three patients with a mean age of

72 (range: 56-84) were treated for two surgical wounds and one radiation wound. All three wounds in this series had failed multiple previous advanced, costly therapies and surgeries with a mean wound duration of 13.2 months.

Mean wound size volume at the start of BGWM was 1.9 cm³.

All wounds healed after a mean of 8.1 weeks with the use of BGWM. 9

■ The result of a small case series suggests that BGWM has a success rate that exceeds the commonly reported industry standard of 50% and 70% of wounds healed; further, it could facilitate an earlier transfer of wound care patients into outpatient care, reduce healthcare costs, and improve quality of life. 10

■ Based on the physiologic properties of bioactive glasses

at the wound interface, this innovative BGWM advanced wound matrix accelerates healing while minimizing the costs of care and improving outcomes.10

■ Mirragen® reduces time to heal by 336 days compared to standard of care. 12

■ Mirragen® has 2.8x faster closure rate than SOC

12

■ In the case series of patients with venous leg ulcers, no

systemic antibiotic therapy was required during the course of treatment with BGWM, suggesting a potential role for the matrix in managing wound bioburden and preventing secondary infections). This finding is noteworthy, given the concerns over antimicrobial resistance and the associated costs of antibiotic therapy. 7

■ The absence of systemic antibiotic therapy during the

course of treatment with BGWM in patients with chronic PG ulcers highlights the potential role of the matrix in managing wound bioburden and preventing secondary infections, 8 which could lead to cost savings by avoiding the need for additional antibiotic treatment.

■ The ease of BGWM application and its ability to promote

wound closure without requiring frequent dressing changes is advantageous from a clinical workflow perspective. 2 ,7 This streamlined approach to wound care may potentially reduce costs associated with frequent dressing changes and clinical visits.

■ Mirragen® results in 38% lower total costs of care over 40 weeks compared to standard of care 2,12

■ Mirragen® requires 53% fewer nursing/physician visits,

contributing to a reduction in labor costs and enhanced cost-effectiveness 12

■ Mirragen® has 35% lower product costs due to a lower average application need, resulting in reduced overall product costs for healed wounds 12

■ Mirragen® leads to 78% lower unhealed wound costs over time, reducing long-term costs for unhealed wounds and saving an average of $8,377 per patient over 40 weeks 12

■ The estimated cost savings per patient between alternate advanced wound therapies and mirragen is $84,000 12

■ The total cost of care (TCOC) of using Mirragen®, compared

to standard of care (SOC) for the treatment of diabetic foot ulcers over a 40 week period was modeled based on results from a 40 patient RCT 2,12

■ Results showed the TCOC for healed patients was $9,233

for Mirragen® versus $20,573 for SOC. The TCOC over the

initial 12 week study was $6,925 per patient for Mirragen® and $5,143 for SOC. When including the cost for unhealed patients over 40 weeks, the total TCOC was $13,698 per patient for Mirragen® compared to $22,074 for SOC 12

■ The study concluded that use of Mirragen® for diabetic

foot ulcers resulted in an estimated cost savings of $8,377 per patient over 40 weeks compared to standard of care.

Mirragen® was found to be a cost-effective option for wound healing 2

■ An economic analysis found use of Mirragen® to be costeffective, with expected cost savings of $8,377 compared to standard care when evaluating total wound healing costs over 40 weeks. 2

■ Potential reduced need to utilise Negative Pressure Wound Therapy (NPWT) costing $119/ day. 12

■ A recent systematic review highlighted that the mean cost of treating diabetic foot ulcers (DFUs) surpasses $31,000, underscoring the economic burden associated with these wounds. 2

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Frequency of Dressings ■ In a randomized controlled trial, Mirragen® doubled the wound area reduction as 12 weeks (79.4% vs. 36.5%) as compared to the standard of care (collagen alginate dressing)2

■ In the case series of patients with venous leg ulcers,

compression wraps consisting of two layers were applied over the BGWM dressings and changed twice weekly at each study visit, along with inspection and reinforcement of the underlying BGWM application as needed. This protocol suggests that BGWM requires less frequent dressing changes compared to standard wound care practices. 7

■ The study involving patients with chronic PG ulcers mentioned

that the BGWM was easy to apply and was used until complete wound closure was achieved for all ulcers 8, indicating a reduced need for frequent dressing changes.

■ The ability of BGWM to facilitate wound closure without

requiring frequent dressing changes is mentioned as an advantage in the management of both venous leg ulcers and PG ulcers, 7 highlighting the potential of the matrix to streamline wound care and reduce the burden of frequent dressing changes on patients and healthcare providers.

■ These detailed findings, supported by the respective

documents, underscore the potential benefits of using BGWM in the treatment of chronic, non-healing wounds, particularly in terms of accelerated healing times, cost reduction through decreased need for systemic antibiotics and frequent dressing changes, and a reduced frequency of dressing changes compared to standard wound care approaches.

Bioactive Glass Wound Matrix Mirragen®

Masterclass GUIDES

Key Points ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■

Mirragen® Bioactive Glass Wound Matrix mimic the microstructure of a fibrin clot.

Mirragen® Bioactive Glass Wound Matrix is biocompatible with living tissues and bioresorbable.

Mirragen® Bioactive Glass Wound Matrix is free of toxic or irritant particles Bioactive Wound Glass fiber absorbs wound fluid to maintain moisture balance Material covers the wound to support a clean environment Mirragen® Bioactive Glass Wound Matrix dissolves over time, eliminating the need to disrupt healing by removing material Fibrous structure allows for gaseous exchange at the wound site Bioactive Wound Glass fiber can conform to any wound shape Mirragen® Bioactive Glass Wound Matrix is synthetic, eliminating the concern over potential disease transmission unlike biologic or cellular tissue-based products Material is stable at room temperature and requires no special storage conditions Mirragen® Bioactive Glass Wound Matrix has a long shelf life of 5 years, and can be stored at room temperature No preparation steps required No tissue tracking required

“I have used Mirragen® on one of my most difficult cases where other skin substitutes did not work. I am impressed by Mirragen®, and I have not been impressed in a long time.” Dr Laurentin Perez Biodegradable and bioabsorbable

Easy to place

Proven safe and effective

Made with natural body elements, Mirragen® dissolves in physiological fluid, so there’s no need to remove it.

Because it’s flexible, easy to use, and will attach to a moist surface, Mirragen® is ideal for challenging wounds, including those that require tunneling or undermining.

Mirragen® has shown great clinical results for a variety of wound types, from easy to heal to complex. In a randomized controlled trial, no adverse events were observed.

References 1. Sen CK. Human Wound and Its Burden: Updated 2020 Compendium of Estimates. Adv Wound Care (New Rochelle). 2021;10(5):281-292.

2. Armstrong DG, Orgill DP, Galiano RD, et al. A multi-centre, single-blinded randomised controlled clinical trial evaluating the effect of resorbable glass fibre matrix in the treatment of diabetic foot ulcers. Int Wound J. 2022 May;19(4):791-801.

3. Jung S, Day T, Boone T, et al. Anti-biofilm activity of two novel, borate based, bioactive glass wound dressings. Biomed. Glasses 2019; 5:67–75.

4. Rahaman MN, Day DE, Bal BS, et al. Bioactive glass in tissue engineering. Acta Biomater. 2011; 7(6): 2355–2373.

5. Mehrabi T, Mesgar AS, Mohammadi Z. Bioactive Glasses: A Promising Therapeutic Ion Release Strategy for Enhancing Wound Healing. ACS Biomater Sci Eng. 2020;6(10):5399-5430.

6. Milne J, Searle R, Styche T. The characteristics and impact of hard-to-heal wounds: results of a standardized survey. J Wound Care 2020;29:282-288.

7. Johnson M, Ortega E, Armstrong D. How Can Novel Bioactive Glass Wound Matrix Optimise Hard-to-Heal Venous Leg Ulcers in Geriatric Patients with Multiple Comorbidities? Wound Masterclass.

2024 Mar 1;3(8).

8. Laurentin-Perez L, Buck D, Rivera D. Bioactive Glass Skin-Substitute Matrix Facilitates Pain Reduction and Healing for Patients with Pyoderma Gangerosum Ulcers . Wound Masterclass. 2024 Mar 1;3(8).

9. Garcia E, Nguyen P. Complex Refractory Wounds: How to Overcome Treatment Recalcitrance and Restore the Treatment Trajectory Using Innovative Biactive Glass. Wound Masterclass.

2024 Mar 1;3(8).

10.Buck, D.W., MD, FACS. Innovative Bioactive Glass Fiber Technology Accelerates Wound Healing and Minimises Costs: A Case Series. Adv Skin Wound Care. 2020; 33(3): 1-6.

11.Jung S, Schultz G, Mafiz AI, Bevels E, Jaskula K, Brownell K, Lantz E, Strickland A. Antimicrobial effects of a borate-based bioactive glass wound matrix on wound-relevant pathogens. J Wound Care.

2023 Dec 7;32(12):763. https://doi.org/10.12968/jowc.2023.32.12.763 12. Buck D. Efficacy and Cost Analysis of Mirragen/ Bioactive Glass Dressing vs. Standard Care. Wound Masterclass. 2024 Mar 1;3(8).

13. Carlos-Reyes, Angeles, et al. “Biological Adaptations of Tumor Cells to Radiation Therapy.” Frontiers in Oncology, vol. 11, 24 Nov. 2021, https://doi.org/10.3389/fonc.2021.718636.

14.Wunderlich, Roland, et al. “Ionizing Radiation Reduces the Capacity of Activated Macrophages to Induce T-Cell Proliferation, but Does Not Trigger Dendritic Cell-Mediated Non-Targeted Effects.”

International Journal of Radiaton Biology, vol. 95, no. 1, 21 Aug. 2018, pp. 33–43, https://doi.org/10.1080/09553002.2018.1490037.

15. Dormand, Emma-Louise, et al. “Radiotherapy and Wound Healing.” International Wound Journal, vol. 2, no. 2, June 2005, pp. 112–127, https://doi.org/10.1111/j.1742-4801.2005.00079.x

16. Glowacki, Julie, et al. “Combined Injury: Irradiation with Skin or Bone Wounds in Rodent Models.” Journal of Radiological Protection: Official Journal of the Society for Radiological Protection, vol. 41, no. 4, 15 Nov. 2021, pubmed.ncbi.nlm.nih.gov/34233299/, https:// doi.org/10.1088/1361-6498/ac125b.

17. Wang, Audrey S., et al. “Corticosteroids and Wound Healing: Clinical Considerations in the Perioperative Period.” The American Journal of Surgery, vol. 206, no. 3, 1 Sept. 2013, pp. 410–417, www.americanjournalofsurgery.com/article/S0002-9610(13)00221-3/pdf, https://doi.org/10.1016/j.amjsurg.2012.11.018.

18. Cai, Zhaobei, et al. “Treatment of Inflammatory Bowel Disease: A Comprehensive Review.” Frontiers in Medicine, vol. 8, no. 765474, 20 Dec. 2021, https://doi.org/10.3389/fmed.2021.765474.

19. Quint, Jennifer K, et al. “Rational Use of Inhaled Corticosteroids for the Treatment of COPD.” NPJ Primary Care Respiratory Medicine, vol. 33, no. 1, 24 July 2023, p. 27, eds.s.ebscohost.com/eds/pdfviewer/pdfviewer?vid=1&sid=acc45220-a8f6-4a65-a81b-ae0 bdb2d8870%40redis, https://doi.org/10.1038/s41533-023-00347-6.

20. Frykberg, Robert G., and Jaminelli Banks. “Challenges in the Treatment of Chronic Wounds.” Advances in Wound Care, vol. 4, no. 9, Sept. 2015, pp. 560–582, www.ncbi.nlm.nih.gov/pmc/articles/PMC4528992/, https://doi.org/10.1089/wound.2015.0635.

21. Han G, Celley R. Chronic wound healing: a review of current management and treatments. Adv Ther 2017:34:593-610.

22. Healthcare Blue Book. www.healthcarebluebook.com. Last accessed Apri 30, 2020.

23. Kim JJ, Francayk M, Gottlieb LJ, Song DH. Cost-effective alternative for negative pressure wound therapy. Plast Reconstr Surg Glob Open 2017,512)e1211.

24.. Dabt.org. www.debt.org/medical. Last accessed April 30, 2020.

25. Centers for Medicare & Medicaid Services. Medicare Previder Utilization and Payment Data, 2019. www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trands-and-Reports/Medicare- Provider-Charge-Data, Last accessed April 30, 2020 26. Miguez-Pacheco V, Hench LL, Boccaccini AR. Bioactive glasses beyond bone and teeth: emerging applications in contact with soft tissues. Acta Biomater 2015;13:1-15.

27. Ottomeyer M. Mohammadkah A, Day D, Westenberg D. Broad-spectrum antibacterial characteristics of four novel borate-based bioactive glasses. Adv Microbiol 2016,6:776-87.

28. Zhang D, Munukka E, Hupa L, Ylänen HO, Vijanen MK, Rupa MM. Factors controlling antibacterial properties of bioactive glasses. Key Eng Mat 2007.830-332.173-6.

29. Haubner, Frank, et al. “Wound Healing after Radiation Therapy: Review of the Literature.” Radiation Oncology, vol. 7, no. 1, 24 Sept. 2012, https://doi.org/10.1186/1748-717x-7-162.

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Masterclass GUIDES Introduction

Hidradenitis Suppurativa Keywords

This Masterclass Guide explains Hidradenitis Suppurativa and its treatments.

What Is Hidradenitis Suppurativa?

■ HS Symptoms ■ HS Stages ■ Chronic inflammatory disease ■ Inflammatory nodules ■ Pus-discharging tunnels

■ Hidradenitis Suppurative ■ HS Diagnosis ■ HS Treatment ■ HS Epidemiology ■ HS Quality of Life

Figure 1: Stages of Hidradenitis Suppurativa.

■ Hidradenitis suppurativa (HS) is a chronic inflammatory disease ■ It primarily affects skin folds like armpits, groin, buttocks, or perianal area

■ Common symptoms include inflammatory nodules, abscesses, and pus-filled tunnels

■ The condition is characterized by recurrent and painful skin lesions

Stage 1

Stage 2

Stage 3

■ HS can cause pain, tenderness, and inflammation in the affected areas

■ The exact cause of HS is not fully understood ■ Factors like genetics, hormones, immune dysfunction, and follicular occlusion may contribute

■ Treatment aims to manage symptoms, reduce inflammation, and prevent new lesions

■ The condition is characterized by recurrent and painful skin lesions ■ Options include medications, lifestyle changes, wound care, and surgical interventions

■ Early HS skin lesions can resemble other skin conditions, such as bacterial abscesses, leading to frequent misdiagnosis

■ This misdiagnosis often results in an average delay of around 7 years in reaching a correct diagnosis

■ Clinicians may use scoring systems to assist in diagnosis, and

patient-reported outcome measures (PROMs) are also utilized for stratification and treatment planning

A Guide to Early Diagnosis ■ Recognition of symptoms: Being aware of the common symptoms

of HS, such as recurring painful nodules, abscesses, and sinus tracts in skin folds, can help in early identification

■ Clinical examination: A thorough physical examination by a

dermatologist is essential for evaluating the nature and location of skin lesions, as well as their chronicity

■ Differential diagnosis: Distinguishing HS from other skin conditions that may present with similar symptoms, such as folliculitis or abscesses, requires careful consideration and expertise

■ Diagnostic criteria: There are no specific laboratory tests or imaging studies available for diagnosing HS. Instead, diagnosis is primarily based on clinical criteria, including the characteristic presentation, distribution, and chronicity of the lesions

■ Specialist referral: If HS is suspected, it is advisable to seek

evaluation from a dermatologist or a healthcare professional experienced in managing HS to ensure an accurate diagnosis and appropriate treatment plan

■ Prompt intervention: Early diagnosis allows for timely initiation

of management strategies, which can help alleviate symptoms, prevent disease progression, and minimize complications

Figure 2:

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Wound Masterclass - Vol 3 - March 2024

■ Diagnostic delay: The average delay in diagnosing HS can lead to

a delay in initiating appropriate treatment, resulting in prolonged suffering and disease progression

Masterclass GUIDES

Hidradenitis Suppurativa

UNEMPLOYMENT

EMBARRASSMENT

DEPRESSION

PAIN

IMPAIRED SELF IMAGE

NO EFFECTIVE TREATMENT

Quality of Life

Pain and disease severity:

Sleep disturbances:

Emotional and psychological impact:

The majority of HS patients experience pain, and the severity of pain often correlates with the severity of the disease. Pain can affect daily activities and quality of life.

Insomnia or disturbed sleep due to pain is a common complaint among HS patients. Pain can disrupt sleep patterns, leading to fatigue and decreased well-being.

HS is a disfiguring condition, causing embarrassment and negatively affecting self-esteem. Patients, especially women, may experience impaired sexual lives. The burden on personal and private life can lead to depression, which is correlated with impaired self-image and an increased risk of suicide.

Work and employment issues:

Social isolation:

Impaired mobility:

HS can result in absenteeism from work and higher unemployment rates compared to the general population. The physical and emotional challenges of the condition can make it difficult for patients to maintain regular employment.

HS can lead to social isolation and withdrawal due to embarrassment about the appearance of the lesions, odor associated with the condition, and the fear of judgment or misunderstanding from others.

The pain, inflammation, and recurrent lesions of HS can limit mobility and physical activities, further impacting daily life and overall wellbeing.

Financial burden:

Coexistence of other health conditions:

Impact on relationships:

HS can result in increased healthcare expenses, including doctor visits, medications, and potential surgical interventions. The financial burden may be exacerbated by work absenteeism or unemployment.

Patients with HS may also have a higher prevalence of other health conditions such as obesity, metabolic syndrome, and autoimmune diseases, further adding to the overall disease burden.

HS can strain personal relationships, including intimate partnerships and friendships, due to the physical and emotional challenges associated with the condition.

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Masterclass GUIDES

Hidradenitis Suppurativa

A Guide to Select the Right Treatment

Antibiotic Therapy Antibiotics, such as tetracyclines, clindamycin, and rifampicin, are commonly used in the treatment of HS. They help reduce bacterial colonization and inflammation, providing symptomatic relief.

Anti-inflammatory Therapy Various anti-inflammatory medications may be prescribed, including non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. These medications can help manage pain, reduce inflammation, and control disease activity.

Surgical Intervention In cases where medications alone fail to adequately control HS, surgical interventions may be considered. Procedures such as incision and drainage of abscesses, excision of affected areas, and reconstructive surgery can be performed to remove affected tissue and promote healing.

Combination Therapy Treatment often involves a combination of antibiotic therapy, anti-inflammatory medications, and surgical interventions tailored to individual patient needs.

Limited Effective Therapies Despite the available treatment options, HS remains challenging to manage. Some patients may not respond well to existing therapies, emphasizing the need for continued research and the development of new treatment approaches.

Multidisciplinary Care The management of HS often requires a multidisciplinary approach, involving dermatologists, wound care specialists, and potentially other healthcare professionals such as pain specialists, psychologists, and nutritionists, to address the various aspects of the condition.

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Masterclass GUIDES

Hidradenitis Suppurativa Key Points

■ HS is a chronic inflammatory disease characterized by skin lesions such as inflammatory nodules, abscesses, and pus-discharging tunnels ■ The condition primarily affects skin folds in areas like the armpits, groin, buttocks, or perianal region ■ HS often presents with symptoms that mimic other skin diseases, leading to misdiagnosis and diagnostic delays averaging around 7 years ■ Pain and disease severity in HS are commonly reported, with a correlation between the two ■ Insomnia or disturbed sleep due to pain are common complaints among HS patients ■ HS can be disfiguring, leading to embarrassment and impacting the sexual lives of patients, particularly in women ■ Absenteeism from work and higher unemployment rates are observed in HS patients compared to the general population

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References 1. Zouboulis CC, Desai N, Emtestam L, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. J Eur Acad Dermatol Venereol. 2015;29(4):619-644.

2. Alikhan A, Sayed C, Alavi A, et al. North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations. J Am Acad Dermatol. 2019;81(1):7690.

3. Ingram JR, Piguet V, Chua SL, et al. Topical and systemic therapies for hidradenitis suppurativa: a systematic review. Semin Cutan Med Surg. 2017;36(2):55-63.

4. Revuz JE, Canoui-Poitrine F, Wolkenstein P, et al. Prevalence and factors associated with hidradenitis suppurativa: results from two case-control studies. J Am Acad Dermatol. 2008;59(4):596-601.

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tent_id:653422111 content_id:653422111 content_id:653422111

Masterclass GUIDES Introduction This guide introduces M.O.I.S.T., an acronym which relates to an evidence-based concept that has been developed for the systematic planning of the local treatment of chronic wounds. By introducing the different elements of the concept and providing guidance on how to adopt the principles of M.O.I.S.T. into routine clinical practice, it is hoped that this guide will be of use to both specialists and generalists involved in the care of patients with chronic wounds.

What is M.O.I.S.T.?

The M.O.I.S.T. Concept Guide for Clinicians

Keywords ■ M.O.I.S.T. Concept ■ Chronic Wounds ■ Wound Care ■ Wound Healing

■ Wound Treatment ■ Local Therapy ■ Oxygen ■ Moisture Management

Figure 1: The patient should be at the centre of all wound care. The outer circle represents interventions that fall outside of the scope of M.O.I.S.T., such as compression therapy for venous leg ulcer management and off-loading for diabetes-related foot ulcers.

■ M.O.I.S.T. is an acronym for a concept that was developed with

regard to the multitude of products available to help standardise the local treatment of chronic wounds

■ A concept intended to provide healthcare professionals with

guidance for systematic planning and delivery of local therapy of patients with chronic wounds1

■ Chronic wounds pose a significant challenge, both clinically (i.e.,

to patients) and economically (i.e., to health care providers).

Furthermore, the development of new technologies for the local treatment of wounds is increasing

■ The ‘M’ stands for moisture balance, the ‘O’ for oxygen balance,

the ‘I’ for infection control, ‘S’ for supporting strategies, and ‘T’ for tissue management

■ The M.O.I.S.T. concept is an educational tool that can be applied

widely in clinical practice to help healthcare professionals systemically plan and deliver local treatment for different types

Who Is M.O.I.S.T. Designed For? ■ The M.O.I.S.T. concept is intended for the care of patients with chronic

How Was M.O.I.S.T. Developed?

wounds to plan and deliver effective local treatment of chronic wounds

■ The concept can also be used by those involved in educating

healthcare professionals on the topical treatment of wounds

Figure 2: Before implementation a thorough assessment of the patient and the wound should be undertaken

■ An international, multi-disciplinary expert panel, on behalf of

WundDACH (umbrella organisation of wound care societies in German-speaking countries), identified an opportunity to develop an educational tool that could be implemented in clinical practice to help healthcare professionals systematically plan and deliver local treatment for chronic wounds in a systematic manner, using the most recent technological advances

■ M.O.I.S.T. evolved from the refinement of another concept for the

local treatment of chronic wounds known by the acronym T.I.M.E. (the ‘T’ stands for tissue, the ‘I’ for infection and inflammation, the ‘M’ for moisture balance and the ‘E’ for edge of the wound)5

■ The ‘T’, ‘I’ and ‘M’ elements of T.I.M.E. were considered by the expert

panel to be still highly applicable and so they were included (with some minor modifications) in the M.O.I.S.T. concept. The letter ‘E’ of the T.I.M.E. concept covers a wide array of interventions for wound bed preparation and the promotion of healing, such as debridement, skin grafts, and biological therapies. There is no ‘E’ element in the M.O.I.S.T. concept; instead ‘O’ for oxygen balance and ‘S’ for supporting strategies are included, thus allowing for the inclusion of new treatment options for targeted therapy in a much more differentiated fashion

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Masterclass GUIDES

The M.O.I.S.T. Concept Guide for Clinicians

What Are the Elements of M.O.I.S.T.?

What Are the Options for Treatment?

M – Moisture Balance

O – Oxygen Balance

I – Infection Control

S – Support

T – Tissue Management

A wound's inability to heal can result from either excessive dryness or excessive moisture.

There are various methods for delivering topical oxygen therapy.

Moisture balance is an essential component for effective wound healing.

These include: continuous oxygen delivery, low constant pressure oxygen in a contained chamber, higher cyclical pressure oxygen, oxygen released through dressings or gels, oxygen transfer via haemoglobin, and the application of oxygen species.

Topical antimicrobial products should be used in accordance with antimicrobial stewardship principles and local protocols, as well as official national and international guidelines.

When problematic wounds are treated but do not heal as expected, strategies to rebalance the environment of the wound bed can get healing back on track.

Debridement methods include autolytic, biological, mechanical, sharp, surgical, and enzymatic techniques. debridement, wound cleansing, granulation as well as re-epithelialization.

Treatment options include: Antiseptics, medicinal honey, Dialkylcarbomoyl chloride (DACC)-coated dressings, silver coated dressings.

A range of therapeutic amd treatment options are available to stimulate healing.

There are a range of dressings which preserve moisture levels.

Consistency of the exudate also plays a role in dressing selection.

Wound gels can add moisture.

Alginates, fibre gelling, foams and superabsorbers absorb exudate and other fluids.

Treatment Options include: Haemoglobin spray, hyperbaric or normobaric oxygenation.

Examples include the use of growth factors, topical wound scaffolds, and local stem cell therapy.

Specialised dressings or physical therapies like negative pressure wound therapy (NPWT), electrical stimulation or ultrasound can enhance the effects of debridement.

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Masterclass GUIDES

The M.O.I.S.T. Concept Guide for Clinicians

How to Integrate M.O.I.S.T. Into Your Clinical Practice

M – Moisture Balance For several decades, moist wound therapy has been the gold standard in the treatment of chronic wounds.4 In this context, it is essential to achieve an equilibrium between too little and too much moisture in wounds. Accordingly, dry wounds require the addition of moisture, for example, through hydrogels.

Usually, however, there is an excess of moisture, thus requiring the use of wound products such as superabsorbers.

O – Oxygen Balance With respect to the pathophysiology of chronic wounds, hypoxia plays a key role in nearly all types of wounds.9 As regards topical treatment, this means that – especially if measures such as revascularization and compression therapy have been insufficient – there are therapeutic options available to restore oxygen balance. Here, adjuvant treatments include wound dressings or sprays as well as normobaric or hyperbaric oxygen therapy.10,11

I – Infection Control Infection control describes all antimicrobial strategies. Usually, systemic antibiotic treatment is only indicated for genuine infections.12 In order to prevent infections, eradicate multiresistant pathogens (MRPs), or treat local infections, antiseptics such as polyhexanide and octenidine or wound dressings with antimicrobial effects, containing silver, honey, or dialkyl carbamoyl chloride (DACC), are commonly used in the topical treatment of chronic wounds.4

S – Support In case of recalcitrant wounds despite apparently adequate treatment, specific wound therapies may be used that actively affect the impaired wound healing process. The promotion of wound healing is achieved, for example, through a decrease in metalloproteinases (MMPs),13 lowering the pH,14 or the application of growth factors.13 While first tools to measure the various aspects have been developed, they are currently not used on a regular basis in daily clinical practice.15

T – Tissue Management Tissue management describes all measures aimed at wound bed preparation, and primarily includes the various methods of debridement and wound cleansing, for example, with preserved solutions such as hypochlorous acid.16 Subsequent wound preparation may also comprise drug-free wound dressings or physical measures such as negative pressure, electricity, or ultrasound.4 Adjuvant use of these therapies has beneficial effects on debridement, wound cleansing, granulation as well as re-epithelialization.

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Collagenases (MMP-1,8,13) Type I,II,III Collagen Proteoglycans

Stromelysins (MMp-3,7 y 10) Type III,IV,V collagen Proteoglycans Fibronectin Laminin

MMP Others (MMP-11,12) Gelatin Fibronectin Laminin

Gelatinases (MMP-2 y 9) Gelatin Type IV,V,VII,X Collagen

MT-MMPs (MMP-14,15,16) Types I,II,IV collagen Gelatin Elastin

Masterclass GUIDES

The M.O.I.S.T. Concept Guide for Clinicians

What is the evidence so far for M.O.I.S.T. ?

Th This evidence-based review will explore each component of the M.O.I.S.T. concept in detail, discussing the scientific rationale and available evidence.e M.O.I.S.T. concept provides a comprehensive

framework for the local management of chronic wounds, addressing key aspects of wound healing such as moisture balance, oxygen balance, infection control, supporting strategies, and tissue management. It is important to note that not all components of the M.O.I.S.T. concept need to be applied to every patient; rather, healthcare professionals should assess each aspect's applicability based on a thorough wound assessment. Additionally, the implementation of therapies according to the M.O.I.S.T. concept does not necessarily need to be sequential, as many treatment methods may address multiple components simultaneously. When selecting wound care products, individual patient needs and economic factors should be considered in a shared decision-making process.

■ Chronic wounds remain a significant healthcare challenge,

affecting approximately 1% of the adult population worldwide, with prevalence expected to rise due to an aging population (Dissemond et al., 2022). Successful management of chronic wounds requires a holistic approach that addresses the underlying etiology and provides evidence-based local wound care to support healing and prevent complications. The M.O.I.S.T. concept, developed by a multidisciplinary expert group, aims to standardize clinical practice and guide healthcare professionals in selecting appropriate wound care products and therapies.

■ Moisture Balance:

Maintaining an optimal moisture balance is crucial for wound healing. Excessive moisture can lead to maceration and delayed healing, while insufficient moisture can result in desiccation and impaired cellular migration (Ousey et al., 2016). The benefits of moist wound healing were first demonstrated by George D. Winter in 1962, and since then, numerous clinical studies have confirmed the advantages of this approach (Dissemond et al., 2022). The choice of wound dressings should be based on factors such as wound healing phases, exudate volume, and viscosity. For example, dry wounds can be moistened with hydrogels, while wounds with excess exudate may benefit from alginates, gelling fibers, foams, superabsorbents, or negative pressure wound therapy (NPWT) (Dissemond et al., 2022). A systematic review by Junker et al. (2013) concluded that moisture-retentive dressings, such as hydrocolloids and alginates, were associated with faster healing rates compared to traditional gauze dressings.

■ Oxygen Balance:

Adequate oxygen supply is essential for wound healing, as it supports cellular metabolism, collagen synthesis, and angiogenesis (Kimmel et al., 2016). Chronic wounds often experience prolonged hypoxia, with partial pressure of oxygen (pO2) values below 30 mmHg, leading to impaired wound healing (Dissemond et al., 2022).

Various methods for measuring tissue oxygenation, such as nearinfrared spectroscopy and transcutaneous oxygen tension, can help confirm the presence of hypoxia (Dissemond et al., 2022). In recent years, several therapeutic approaches for local oxygen therapy have been developed, including portable oxygen generators, low-pressure constant-pressure devices, higher pressure oxygen devices with humidification, oxygen-releasing dressings or gels, and hemoglobin-based oxygen carriers (Dissemond et al., 2022).

Growing evidence supports the use of local oxygen therapy in promoting healing of refractory chronic wounds (Gottrup et al., 2017). The International Working Group on the Diabetic Foot (IWGDF) guidelines recommend local oxygen therapy for the treatment of diabetic foot ulcers (Dissemond et al., 2022).

■ Infection Control:

Infection is a major barrier to wound healing and can lead to serious complications, such as sepsis and amputation (Swanson et al., 2016). Diagnosing wound infections can be challenging, but validated tools such as the Therapeutic Index for Local Infections (TILI) score and the diabetic foot infection wound score can assist clinicians (Dissemond et al., 2022). Infection control strategies include proper wound cleansing, debridement, and the use of topical antimicrobials (antiseptics) rather than topical antibiotics (Dissemond et al., 2022).

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Biofilms, which are communities of microorganisms embedded in an extracellular polymeric substance, can contribute to chronic wound infections and delay healing (Dissemond et al., 2022).

Targeted antibiofilm strategies, such as the use of octenidine, polihexanide, hypochlorous acid, and silver, have shown efficacy against planktonic bacteria (Dissemond et al., 2022). Novel antimicrobial approaches, such as dressings with hydrophobic interactions, hydroresponsive dressings, and cold atmospheric plasma therapy, are also being explored (Dissemond et al., 2022).

Regular review of infection control strategies every 10-14 days is recommended to assess the need for continuation or modification of the treatment regimen (Dissemond et al., 2022).

■ Supporting Strategies:

Supporting strategies encompass a diverse group of wound care products designed to actively target dysfunctional processes in wound healing. One primary focus is the management of matrix metalloproteinases (MMPs), which are often imbalanced in the microenvironment of chronic wounds (Dissemond et al., 2022).

Wound care products containing collagen, cellulose, polyhydrated ionogens-5, or sucrose octasulfate have been developed to modulate MMP activity (Dissemond et al., 2022). Randomized controlled trials have provided evidence supporting the use of sucrose octasulfate in promoting wound healing (Edmonds et al., 2018; Munter et al., 2017). Growth factors, such as platelet-derived growth factor, granulocyte-macrophage colony-stimulating factor, and epidermal growth factor, have also been employed to support wound healing (Dissemond et al., 2022). Biological products, including amniotic membrane, adipose-derived stem cells, and mesenchymal stem cells, as well as skin substitute products, are being investigated for their potential to promote healing (Dissemond et al., 2022). Other innovative approaches include local therapies with negatively charged microspheres, chitosan, coagulation factors, and extracellular matrix proteins (Dissemond et al., 2022). As measurement methods for assessing the wound microenvironment become more advanced, personalized therapies targeting specific aspects of the wound milieu may become more feasible (Dissemond et al., 2022).

■ Tissue Management:

Tissue management refers to all measures of local wound therapy that contribute to wound bed preparation, including wound cleansing, debridement, and the use of wound dressings or physical therapies (Dissemond et al., 2022). Wound cleansing involves the removal of nonadherent components using sterile or preserved solutions and is considered part of the gold standard of modern wound care (Dissemond et al., 2022). Debridement, which is the removal of adherent, dead tissue, crusts, or foreign bodies, is essential for preventing and combating wound infections, biofilm formation, improving wound assessment, and promoting healing (Dissemond et al., 2022). Various debridement methods exist, including surgical, mechanical, biosurgical (maggot therapy), autolytic, proteolytic (enzymatic), and technical (hydrosurgery, lasers, ultrasound) (Dissemond et al., 2022). Following debridement, neutral wound dressings or physical therapies such as negative pressure wound therapy (NPWT) can be employed.

NPWT has demonstrated efficacy in improving wound healing in various types of chronic wounds (Anghel & Kim, 2016).

Masterclass GUIDES

The M.O.I.S.T. Concept Guide for Clinicians

Key Points

■ The M.O.I.S.T. concept, developed in 2017 by an expert group (WundDACH), is an evolution of the T.I.M.E. clinical decision tool and is primarily an educational tool for the local treatment of chronic wounds.

■ Each letter of M.O.I.S.T. describes an element of topical chronic wound management: Moisture balance, Oxygen balance, Infection control, Supporting strategies, and Tissue management.

■ The M.O.I.S.T. concept should be applied after a full patient assessment and in conjunction with other therapeutic interventions to manage underlying wound pathologies, as part of a holistic approach to wound management.

■ The M.O.I.S.T.-based treatment recommendations are a step towards consistent care for local wound therapy that can be implemented alongside existing protocols and guidelines.

References 1. Sen, C.K. Human wound and its burden: updated 2020 compendium of estimates. Advances in Wound Care (New Rochelle) 2021;10:281-292.

2. Mirhaj, M., Labbaf, S., Tavakoli, M., Seifalian, A.M. Emerging treatment strategies in wound care. International Wound Journal 2022;19:1934-1954.

3. Dissemond, J., Assenheimer, B., Gerber, V., Kurz, P., Lauchli, S., Panfil, E.M., Probst, S., Traber, J., Strohal, R. Lokaltherapie chronischer Wunden; das M.O.I.S.T. konzept. Deutsche Medizinische Wochenschrift 2023;148:400-405.

4. Dissemond, J., Malone, M., Ryan, H., Tanaka, R., Ohura, N., Wong, K.L., AiLing, H., Long, Z., Yoon, K.J., Angspatt, A., Nair, H.K.R. Implementation of the M.O.I.S.T. concept for the local treatment of chronic wounds into clinical practice. Wounds International 2022;13:34-43.

5. Schultz, G.S., Barillo, D.J., Mozingo, D.W., Chin, G.A., Wound Bed Advisory Board Members. Wound bed preparation and a brief history of TIME. International Wound Journal 2004;1(1):19-32 6. Anghel, E. L., & Kim, P. J. (2016). Negative-Pressure Wound Therapy: A Comprehensive Review of the Evidence. Plastic and Reconstructive Surgery, 138(3S), 129S-137S. https://doi.org/10.1097/PRS.0000000000002645 7. Bergin, S., Wraight, P., & Silver, T. (2014). Silver based wound dressings and topical agents for treating diabetic foot ulcers. Cochrane Database of Systematic Reviews, 2014(1), CD005082. https://doi.org/10.1002/14651858.CD005082.pub3 8. Castilla, D. M., Liu, Z.-J., & Velazquez, O. C. (2012). Oxygen: Implications for Wound Healing. Advances in Wound Care, 1(6), 225-230. https://doi.org/10.1089/wound.2011.0319 9. Dumville, J. C., Stubbs, N., Keogh, S. J., Walker, R. M., & Liu, Z. (2015). Hydrogel dressings for treating pressure ulcers. Cochrane Database of Systematic Reviews, 2015(2), CD011226. https://doi.org/10.1002/14651858.CD011226.pub2 10. Fierheller, M., & Sibbald, R. G. (2010). A Clinical Investigation into the Relationship between Increased Periwound Skin Temperature and Local Wound Infection in Patients with Chronic Leg Ulcers. Advances in Skin & Wound Care, 23(8), 369-379. https://doi.org/10.1097/01.ASW.0000383197.28192.98 11. Gottrup, F., Dissemond, J., Baines, C., Frykberg, R., Jensen, P. Ø., Kot, J., Kröger, K., & Longobardi, P. (2017). Use of Oxygen Therapies in Wound Healing. Journal of Wound Care, 26(Sup5), S1-S43. https://doi.org/10.12968/jowc.2017.26.Sup5.S1 12. Junker, J. P. E., Kamel, R. A., Caterson, E. J., & Eriksson, E. (2013). Clinical Impact Upon Wound Healing and Inflammation in Moist, Wet, and Dry Environments. Advances in Wound Care, 2(7), 348-356. https://doi.org/10.1089/wound.2012.0412 13. Karlsson, M., Lindgren, M., Jarnhed-Andersson, I., & Tarpila, E. (2015). Dressing the split-thickness skin graft donor site: A randomized clinical trial. Advances in Skin & Wound Care, 28(1), 20-25. https://doi.org/10.1097/01.ASW.0000459844.40840.25 14. Kimmel, H. M., Grant, A., & Ditata, J. (2016). The Presence of Oxygen in Wound Healing. Wounds: A Compendium of Clinical Research and Practice, 28(8), 264-270. https://pubmed.ncbi.nlm.nih.gov/27560469/ 15. Kirsner, R. S., Delhougne, G., & Searle, R. J. (2019). A Pooled Analysis of the Safety and Efficacy of Negative Pressure Wound Therapy for the Treatment of Chronic Wounds. Wounds: A Compendium of Clinical Research and Practice, 31(3), 73-80. https://pubmed.ncbi.nlm.nih.gov/30720443/ 16. Leaper, D., Assadian, O., Edmiston, C. E., & Karahan, M. (2015). Approach to chronic wound infections. British Journal of Dermatology, 173(2), 351-358. https://doi.org/10.1111/bjd.13677 Lewis, J., & Lipp, A. (2013). Pressure-relieving interventions for treating diabetic foot ulcers. Cochrane Database of Systematic Reviews, 2013(1), CD002302. https://doi.org/10.1002/14651858.CD002302.pub2 17.McGuiness, W., Vella, E., & Harrison, D. (2004). Influence of dressing changes on wound temperature. Journal of Wound Care, 13(9), 383-385. https://doi.org/10.12968/jowc.2004.13.9.26702 Norman, G., Dumville, J. C., Mohapatra, D. P., Owens, G. L., & Crosbie, E. J. (2016). Antibiotics and antiseptics for surgical wounds healing by secondary intention. Cochrane Database of Systematic Reviews, 2016(3), CD011712. https://doi.org/10.1002/14651858.CD011712.pub2 18.Ousey, K., Cutting, K. F., Rogers, A. A., & Rippon, M. G. (2016). The importance of hydration in wound healing: Reinvigorating the clinical perspective. Journal of Wound Care, 25(3), 122-130. https://doi.org/10.12968/jowc.2016.25.3.122 19. Saco, M., Howe, N., Nathoo, R., & Cherpelis, B. (2016). Comparing the efficacies of alginate, foam, hydrocolloid, hydrofiber, and hydrogel dressings in the management of diabetic foot ulcers and venous leg ulcers: A systematic review and meta-analysis examining how to dress for success. Dermatology Online Journal, 22(8), 13030. https://pubmed.ncbi.nlm.nih.gov/27617934/ 20. Simões, D., Miguel, S. P., Ribeiro, M. P., Coutinho, P., Mendonça, A. G., & Correia, I. J. (2018). Recent advances on antimicrobial wound dressing: A review. European Journal of Pharmaceutics and Biopharmaceutics, 127, 130-141. https://doi.org/10.1016/j.ejpb.2018.02.022 21. Swanson, T., Angel, D., Sussman, G., Cooper, R., Haesler, E., Ousey, K., Carville, K., Fletcher, J., Kalan, L., Keast, D., Leaper, D., Schultz, G., Black, J., & Call, E. (2016). Wound infection in clinical practice: Principles of best practice. International Wound Journal, 13(5), 1-11. https://doi.org/10.1111/ iwj.12643.

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TRIPLE

WOUND HEALING

Utilising LevaFiber™ technology, Drawtex® is a highly effective wound management solution, with triple-action wound healing to remove harmful exudate from chronic wounds, while leaving healthy granulation tissue in place.

Capillary action Draws wound exudate & debris into the dressing Hydroconductive action Lifts, holds & transfers the exudate away from the wound bed, both vertically & horizontally Electrostatic action During wound exudate contact, the surface charge of the dressing facilitates the absorption & removal of large amounts of exudate, bacteria & waste material

Drawtex® effectively manages & removes exudate, devitalised tissue, bacteria, wound debris, harmful MMPs & biofilm nutrients from the wound bed 1, 2 References: 1. Couch K. Discovering hydroconductive dressings. Ostomy Wound Manage. 2012;58(4):8-10 | 2. Wolcott RD, Cox S. The effect of hydroconductive dressings on the suppression of wound biofilm. Wounds. 2012;24(5):132-137.

Drawtex Healhcare Europe (responsible for Europe WE medical BV ) info@drawtex.eu I www.drawtex.com info@wemedical.nl I www.wemedical.nl

Bioelectric Stimulation, Electric Fields and the Current of Injury: Have We Been Overlooking One of the Most Important Coordinators of the Wound Healing Process?

Editorial Summary This article presents a critical examination of bioelectric stimulation, electric fields, and the current of injury as potentially overlooked yet fundamental coordinators in wound healing. It elucidates the physiological basis of bioelectricity in cellular processes and its implications for clinical wound management.

The review explores the role of membrane potentials, transepithelial potentials, and bioelectric signaling in modulating key cellular behaviors crucial to healing, including proliferation, migration, and differentiation.

It introduces the concept of the "skin battery" and how its disruption generates a "current of injury," which initiates and sustains the healing cascade.

Compelling evidence suggests that compromised bioelectric processes may underlie impaired healing in recalcitrant wounds, particularly in geriatric and diabetic populations. The article critically evaluates the efficacy of exogenous electrical stimulation therapy (EST), citing meta-analyses demonstrating significant improvements in healing rates for hard-to-heal wounds.

While acknowledging the limitations of earlier EST devices, the authors highlight recent advancements in microcurrent technology that offer more practical and integrable solutions for clinical application. They posit that incorporating bioelectric-based therapies could potentially address the increasing prevalence of chronic wounds more effectively than conventional approaches focused solely on biochemical mediators.

This comprehensive review advocates for a paradigm shift in wound care strategies, urging clinicians to consider bioelectric factors as essential components in the multifaceted approach to wound healing.

Introduction

D

elve into any Wound Management textbook and you will learn all about the biochemical basis of wound healing - the complex interplay between growth factors, cytokines, proteases, cell membrane receptors and so on, which drive the wound healing process. However, scientists are becoming clearer that while these factors are indeed important stimulators, a much more fundamental coordinator of healing behaviours that is triggered by wounding is not even mentioned in most wound management texts.1 We are referring to bioelectricity.

Imagine that the growth factors and cytokines are the musicians in an orchestra, then bioelectricity is the conductor, making sure they are all co-ordinated and working in harmony to restore skin back to pre-wounded state.

Dr Robin Martin Freelance Scientific Consultant, Robin Martin PhD Scientific Consulting Foggathorpe, United Kingdom

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The purpose of this document is to describe the physiological basis of bioelectricity and to explain the fundamental importance of bioelectrical fields and currents in the wound healing process.

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Let’s Start With the Basics; The Membrane Potential in Cell Biology All higher organisms, including humans, are organised into organs, the basic units of which are cells. The membrane enveloping each cell separates the highly organised system inside the cell from the environment outside the cell and the composition of the fluid inside the cell is very different from the composition of the extracellular fluid. One key difference is that the levels of electrolytes, for example Ca2+, Na+, K+, Cl- ions, vary between the inside and outside of the cells.

Under normal conditions, more positively charged electrolytes (predominantly Na+ and K+ ions) are found outside the cell than inside the cell. In addition, proteins are generally negatively charged and these are retained inside the cell. The overall effect is that the cytoplasm inside the cell has an electrically negative charge compared with the surrounding extracellular fluid. The difference in this electrical charge on either side of the membrane is called the membrane potential and measures 40-80mV.2 Essentially, there is a potential difference between the inside and the outside of the cell meaning that each cell can act as a tiny battery that stores ‘bioelectricity’ (Figure 1).

Bioelectric Stimulation, Electric Fields and the Current of Injury

“The membrane potential has a purpose; when something happens to disrupt it, this drives a movement of electrically charged ions, which then stimulate the cell to change its cellular processes and behaviours.”

Figure 1: Membrane potential. All living cells, including human cells, have a different composition inside and outside their cell membranes.

Differences in the concentration of charged molecules (like ions and proteins) between the inside and the outside of the cell generates a membrane potential. This is in effect a difference in electrical charge on either side of the cell membrane, which allows each cell to act as a tiny battery.

How Bioelectric Signalling Works The membrane potential has a purpose; when something happens to disrupt it, this drives a movement of electrically charged ions, which then stimulate the cell to change its cellular processes and behaviours. We most often think about this happening in the context of nerve cells being stimulated to fire off a nerve impulse, but in reality these kinds of events happen in all cells in the human body.

Figure 2: How disrupting the membrane potential can drive bioelectric signalling. Bioelectric signalling can be initiated in 3 main ways, all of which can result in signalling events inside the cell which trigger gene transcription, protein synthesis and essentially activate a range of cell behaviours.

Disruption to the membrane potential can happen in at least three different ways. Firstly, ion channels in the membrane can open, allowing ions to flood in or out, changing the charge across the cell membrane. Secondly, structures called gap junctions that connect neighbouring cells can open or close, either transmitting or blocking changes from one cell into its neighbours. Thirdly, minor physical damage to an individual cell’s membrane can allow diffusion of molecules from the inside or outside of the cell (Figure 2).2

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“The electrical properties of epithelia are hardly ever mentioned in textbooks. Yet these properties are very important for organ function.” 1

In all of these scenarios, the membrane potential of the cell is suddenly changed by a movement of charged ions and proteins across the cell membrane. This change can trigger a wide variety of cellular responses and is collectively termed bioelectric signalling. When the membrane potential is disrupted, and the biochemical composition of the cytoplasm changes, receptors inside the cells respond to these changes by initiating gene expression and the synthesis of proteins through gene transcription and translation. Such cell activation can change the behaviour of a cell.

Some changes triggered by bioelectric signalling include: cell proliferation, cell migration, cell differentiation and cell directional polarisation, among others. These are all cellular behaviours that are important drivers of the healing process.2 Transepithelial Potential and the ‘Skin Battery’ In the previous section we described how bioelectricity is created by the potential difference between different compartments, for example inside and outside the cell.

But bioelectricity can also be observed across different compartments of tissue for example the outermost (apical) and innermost (basolateral) surfaces of epithelial tissues.

Transepithelial potential has been measured in skin, gut epithelia, kidney and cornea.3 In the skin, the transdermal potential is commonly referred to as the ‘skin battery’.

Intact skin has a transdermal potential of 15 to 50mV with the inside being positively charged relative to the outside (Figure 3A).4,5 The transepidermal potential is generated in the keratinocyte layers of the epithelium because of a net movement of sodium ions (Na+, positively charged) from the apical side of the cell (the outermost edge) through the cell, to the basolateral (innermost) edge.1,4,6 All cells have sodium channels, potassium channels and sodium-potassium pumps, and in most

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cells these structures are randomly positioned around the perimeter of the cell. However, in keratinocytes that make up the epidermis, they are polarised with most sodium channels being localized to the apical (outermost) membrane, most potassium channels being found in the basolateral membrane (innermost layer of keratinocytes) and most sodium-potassium pumps also localised along the basal side where they pump sodium ions out of the cell in the direction of the dermis.1,4,6 The positioning of the sodium ions themselves is in constant flux; once they have been removed from the cell at the basolateral side, they try to diffuse down their concentration gradient towards the apical edge, however gap junctions that tightly bind keratinocytes to their neighbours, prevent free diffusion.6 The positively charged ions at the basolateral side are not able to diffuse away which leads to there being a trans-epidermal potential (Figure 3B).

Figure 3: How transdermal potential is generated in human skin.

Figure 3A. Human skin is electrically charged with a relatively positive charge on the basolateral side of the epidermis (next to the dermis). This electrical charge has led to the skin being described as a battery. Figure 3B represents a layer of within the epithelium. Sodium channels on the apical side of the keratinocytes pump sodium into the cell. Sodium-potassium pumps situated on the basolateral side of the cell then eject the sodium from the cell. The sodium is not able to diffuse back to the apical side of the cell because it is blocked by the presence of tight junctions that tightly link keratinocytes to their neighbours and forms an impermeable barrier. Therefore, the basolateral side has a higher concentration of sodium ions and their positive charge generates a transmembrane potential that is positive on the basolateral side and negative on the apical side.

Bioelectric Stimulation, Electric Fields and the Current of Injury

“All cells in tissue at the edge of the wound are exposed to this current of injury which stimulates their activity for several days after wounding. In normal wound healing, this wound-induced electrical field persists until the migrating epithelium reseals the wound and re-establishes tight junctions which create a uniformly high electrical resistance, at which point the wound-induced electrical field drops to zero and the transcutaneous potential, the skin battery, is restored.” 4-6

The ‘Current of Injury’ While intact skin acts as a battery of potential bioelectrical energy, what happens when the skin is wounded? Scientists have known the answer to this question for well over a century, since, in 1843, the scientist Dubois-Reymond first used a galvanometer on his own cut finger and identified that wounds had a measurable electric current.5 This has since been named the ‘current of injury’.

Wounding the epithelial sheet creates a hole that breaches the high electrical resistance established by the tight junctions between the cells, and this short-circuits the epithelium, in the local vicinity of the wound. The transdermal potential therefore drops to zero at the wound.

However, because normal ion transport continues in unwounded epithelial cells beyond the wound edge, the transcutaneous potential difference remains at normal values around 2mm back from the wound.6 It is this gradient of electrical potential, 0 mV at the short-circuited wound bed, 15-50 mV a short distance away in unwounded tissue, that establishes a laterally oriented electrical field and drives a steady

bioelectric flow of current (Figure 4). This is termed the ‘current of injury’ and, in healthy individuals, is around 140mV per mm .4-6 All cells in tissue at the edge of the wound are exposed to this current of injury which stimulates their activity for several days after wounding. In normal wound healing, this wound-induced electrical field persists until the migrating epithelium reseals the wound and re-establishes tight junctions which create a uniformly high electrical resistance, at which point the wound-induced electrical field drops to zero and the transcutaneous potential, the skin battery, is restored.4-6 So, as the wound heals, the current of injury progressively reduces. The current of injury will also gradually decrease if the wound is left open to dry.7 Maintaining a moist wound environment has been recognised for decades as being vital for healing. Given that electrolytes are soluble and need fluid to diffuse, it is highly likely that moist wound healing is essential for the current of injury to exist. Seeing moist wound healing in the context of the movement of electrolytes and the current of injury, provides a new way

Figure 4: The ‘current of injury’. On wounding, there is an immediate, collapse of the transepithelial potential at the site of the wound (to 0mV) caused by loss of an intact epithelium. In adjacent unwounded areas, the ion transport properties of the epithelium remain intact and Na+ continues to be transported inwards towards the basolateral side of the epithelium (narrow black arrows) and prevented from diffusing to the apical side by the presence of intact gap junctions. However, there is no barrier to prevent ions from nearby unaffected areas to flow laterally towards the centre of the wound (blue arrows). This uncontrolled movement of ions towards the centre of the wound can be measured at around 50mV and is known as the current of injury. Adapted from Tyler et al (2017).2

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Bioelectric Stimulation, Electric Fields and the Current of Injury

“Given that electrolytes are soluble and need fluid to diffuse, it is highly likely that moist wound healing is essential for the current of injury to exist.”

of appreciating this basic tenet of wound management.

How Normal Wound Healing Processes Are Reliant on the Current of Injury Many of the fundamental cell behaviours essential to the healing process are stimulated by bioelectric signalling, as evidenced in numerous scientific studies (Figure 5):1,4,6,8,9 •

Proliferation: many cell types need to proliferate for normal wound healing to progress including white blood cells (essential in the inflammatory phase), keratinocytes (for re-epithelialisation), endothelial cells (to make new blood vessels essential for granulation tissue formation) and fibroblasts in the dermis (required to deposit replacement ECM). Bioelectric signalling stimulates proliferation in all of these cell types.1,6

•

Migration: Bioelectric signalling, through cell directional polarisation, is believed to instruct the newly proliferated cells in

which direction to migrate, so, for example, keratinocytes know to migrate towards, not away from the centre of the wound.1,4,6,9 •

Cell differentiation This process is essential in later stages of healing, in particular during the late proliferative stage and throughout the remodelling phase. New keratinocytes need to differentiate to form the layers of the epidermis. Fibroblasts differentiate during the phases of healing as their role changes. During the early proliferative phase fibroblasts are stimulated to rapidly produce ECM which is deposited quickly to close the wound. During the remodelling phase fibroblasts become differentiated into myofibroblasts, which remodel this newly deposited ECM into tissue more like normal dermis. Electric fields have also been shown to coordinate these cell maturation events.8

Figure 5: The cellular processes in wound healing that are reliant on the current of injury.1,4,6,8

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Bioelectric Stimulation, Electric Fields and the Current of Injury

“Not all wounds heal normally and hard-to-heal wounds which remain unhealed for at least 12-months represents some 30% of all wounds treated annually (UK data).” 11

Several studies have been conducted where researchers have used drugs to enhance or decrease ion transport, and therefore the current of injury, in wound healing models. They have found a clear association between the current of injury and the rate of healing – the lower the current, the slower the rate of healing.10 Given that the movement of charged ions is the way in which bioelectricity is ‘delivered’, these studies also demonstrate the central role of bioelectrical signalling on wound healing events.

There is Some Evidence That the Skin Battery and the Current of Injury Are Reduced in Some People Not all wounds heal normally and hard-to-heal wounds which remain unhealed for at least 12-months represents some 30% of all wounds treated annually (UK data).11 Some of the main risks of hard-to-heal wounds include older age, diabetes, poor nutrition and ischaemia. It has been suggested that older people and those with diabetes have reduced or compromised transepidermal potential and a lower current of injury.5,12,13 Research in a volunteer study has shown that the current of injury is 48% lower in older people (aged 65+) than in younger people (aged 18-25).

There were no differences between male and female. This suggests that the skin battery in older people is less efficient than in younger people.5 Other studies have shown that the skin battery (in intact skin) is lower in people with diabetes than in age matched controls, also suggesting that the skin battery is less powerful in people with diabetes, than in people with no diabetes.14 Studies in the cornea, an epithelium that has much in common with the skin and is often used as a model for cutaneous wound healing, have also shown that diabetes reduces the current of injury.15 It’s thought that having a compromised current of injury makes the wound healing process less

efficient – the conductor of the orchestra is not doing the job properly - and this is likely to be one of the reasons why hard-to-heal wounds are more common in these groups of people. More research is needed to fully understand how these factors interplay but it is possible that a compromised current of injury could reasonably be considered a barrier to healing.

In People With Compromised Skin Battery and Compromised Current of Injury, Application of EST at Physiologically Relevant Levels May Be Beneficial For those people with a hard-to-heal wound, who may have a compromised current of injury, there is a promising treatment to promote healing. Electrical stimulation therapy (EST) is a highly evidenced treatment type in the field of hard-to-heal wounds with numerous meta-analyses of randomised controlled trials (of which 3 are described below).16-18 The rationale for applying EST is that by replacing the lost endogenous current it can ‘normalise’ the healing process. Many experts suggest that microcurrent EST may resemble a natural electric field or electric current, enhancing the patient’s own endogenous wound healing processes.2,19 One key meta-analysis focussed on hard-to-heal wounds treated with microcurrent devices. This meta-analysis found that wounds treated with microcurrent devices alongside standard care, reduced significantly more in size and healed significantly faster.17 A separate meta-analysis published by the Cochrane group, but focused on pressure ulcers, showed that compared with standard care alone, wounds treated with electrical stimulation wound therapy are almost twice as likely to heal and have a 4.6% increase per week in the rate of wound healing.20 Aside from stimulating healing, microcurrent electrical stimulation wound therapy has also been shown to significantly reduce wound pain,

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Bioelectric Stimulation, Electric Fields and the Current of Injury starting after only a few days of treatment.21 We know that wound pain is often linked with inflammation, so it may be that the effect of microcurrent EST on pain is related to its ability to dampen down macrophage-mediated inflammatory processes.22 In the past, EST devices designed for use in wound management were expensive, very large and awkward to use. Also, most of these devices weren’t able to be used along-side standard care and this made it difficult to incorporate this potentially beneficial technology into everyday wound care routines. However, a new and innovative device, Accel-Heal Solo, is now available to enable use of this technology in frontline practice.

Conclusion The burden of hard-to-heal wounds is enormous and is growing,11 despite the efforts of dedicated clinicians and scientists alike. The current approaches aren’t working well enough, and we need to do something different. Over the past several decades, much of the research and innovation in wound management has focussed on understanding and modulating the biochemical mediators of the wound healing process, the growth factors and cytokines, without much success.

However, running in parallel, a compelling body of clinical evidence supporting the use of exogenous EST to promote healing in hard-toheal wounds has been steadily growing. What scientists now know about the fundamental role of bioelectricity in coordinating the wound healing process, fits perfectly with this body of evidence and underpins the clinical benefit of applying EST to hard-to-heal wounds. Although in the past these EST devices were difficult to adopt in frontline clinical practice, that is no longer the case and innovative new devices that deliver microcurrent EST are now available that are easily incorporated into existing wound care practice and routines. These microcurrent devices are subsensory and inherently safe, and together with the substantial underlying science and evidence base, this should provide clinicians with the confidence to use in their everyday practice.

Of course, what every healthcare professional wants is to help their patients to achieve respite and to recover from their painful, hardto-heal wounds. We believe that microcurrent EST may help to achieve this goal. In the words of one patient with a painful VLU of 5 months duration, after starting treatment with microcurrent EST* his “leg started to heal and [he] started to get [his] life back”.23 And that is what we want for all our patients! *Accel-Heal, Accel-Heal Limited, Hever, Kent, UK.

Technologies

References 1. Nuccitelli, R. A role for endogenous electric fields in wound healing. Curr Top Dev Biol 58, 1-26 (2003). https://doi.org:10.1016/s0070-2153(03)58001-2 2. Tyler, S. E. B. Nature’s Electric Potential: A Systematic Review of the Role of Bioelectricity in Wound Healing and Regenerative Processes in Animals, Humans, and Plants. Front Physiol 8, 627 (2017). https://doi.org:10.3389/fphys.2017.00627 3. Chifflet, S. & Hernández, J. A. The plasma membrane potential and the organization of the actin cytoskeleton of epithelial cells. Int J Cell Biol 2012, 121424 (2012). https://doi. org:10.1155/2012/121424 4. Martin-Granados, C. & McCaig, C. D. Harnessing the Electric Spark of Life to Cure Skin Wounds. Adv Wound Care (New Rochelle) 3, 127-138 (2014). https://doi.org:10.1089/ wound.2013.0451 5. Nuccitelli, R. et al. The electric field near human skin wounds declines with age and provides a noninvasive indicator of wound healing. Wound Repair Regen 19, 645-655 (2011). https://doi.org:10.1111/j.1524-475X.2011.00723.x 6. McCaig, C. D., Rajnicek, A. M., Song, B. & Zhao, M. Controlling cell behavior electrically: current views and future potential. Physiol Rev 85, 943-978 (2005). https://doi.org:10.1152/ physrev.00020.2004 7. Cheng K et al. An occlusve dressing can sustain natural electric potential of wounds. J Invest Dermatol 104, 662 (1995).

8. Yang, J. et al. Bioelectric fields coordinate wound contraction and re-epithelialization process to accelerate wound healing via promoting myofibroblast transformation. Bioelectrochemistry 148, 108247 (2022). https://doi.org:10.1016/j.bioelechem.2022.108247 9. Zhao, M., Rolandi, M. & Isseroff, R. R. Bioelectric Signaling: Role of Bioelectricity in Directional Cell Migration in Wound Healing. Cold Spring Harb Perspect Biol 14 (2022). https:// doi.org:10.1101/cshperspect.a041236 10. Reid, B. & Zhao, M. The Electrical Response to Injury: Molecular Mechanisms and Wound Healing. Adv Wound Care (New Rochelle) 3, 184-201 (2014). https://doi.org:10.1089/ wound.2013.0442 11. Guest, J. F., Fuller, G. W. & Vowden, P. Cohort study evaluating the burden of wounds to the UK’s National Health Service in 2017/2018: update from 2012/2013. BMJ Open 10, e045253 (2020). https://doi.org:10.1136/bmjopen-2020-045253 12. Kloth, L. C. Electrical Stimulation Technologies for Wound Healing. Adv Wound Care (New Rochelle) 3, 81-90 (2014). https://doi.org:10.1089/wound.2013.0459

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13. Fraccalvieri, M., Salomone, M., Zingarelli, E. M., Rivarossa, F. & Bruschi, S. Electrical stimulation for difficult wounds: only an alternative procedure? Int Wound J 12, 669-673 (2015). https://doi.org:10.1111/iwj.12194 14. Ionescu-Tîrgovişte, C. et al. Study of the cutaneous electric potentials and the perception threshold to an electric stimulus in diabetic patients with and without clinical neuropathy.

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15. Shen, Y. et al. Diabetic cornea wounds produce significantly weaker electric signals that may contribute to impaired healing. Sci Rep 6, 26525 (2016). https://doi.org:10.1038/srep26525 16. Rabbani, M., Rahman, E., Powner, M. B. & Triantis, I. F. Making Sense of Electrical Stimulation: A Meta-analysis for Wound Healing. Ann Biomed Eng (2023). https://doi.org:10.1007/ s10439-023-03371-2 17. Avendaño-Coy, J. et al. Electrical microcurrent stimulation therapy for wound healing: A meta-analysis of randomized clinical trials. J Tissue Viability 31, 268-277 (2022). https://doi. org:10.1016/j.jtv.2021.12.002 18. Girgis, B., Carvalho, D. & Duarte, J. A. The effect of high-voltage monophasic pulsed current on diabetic ulcers and their potential pathophysiologic factors: A systematic review and meta-analysis. Wound Repair Regen 31, 171-186 (2023). https://doi.org:10.1111/wrr.13063 19. Balakatounis, K. C. & Angoules, A. G. Low-intensity electrical stimulation in wound healing: review of the efficacy of externally applied currents resembling the current of injury.

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20. Arora, M. et al. Electrical stimulation for treating pressure ulcers. Cochrane Database Syst Rev 1, Cd012196 (2020). https://doi.org:10.1002/14651858.CD012196.pub2 21. M. Moon, D. Hazel & Hawes., L. Reduction in wound pain associated with electrical stimulation therapy results in a corresponding decrease in analgesic consumption: an evaluation of patients with painful leg ulcers. Presented at Wounds UK, Harrogate, Nov 2023. (2023).

22. Lallyett, C. et al. Changes in S100 Proteins Identified in Healthy Skin following Electrical Stimulation: Relevance for Wound Healing. Adv Skin Wound Care 31, 322-327 (2018). https:// doi.org:10.1097/01.Asw.0000533722.06780.03 23. N. Turner & Ovens., L. Clinical outcome results and quality of life improvements using electroceutical treatment - Patient perspectives. Poster presented at EWMA 2017. (2017).

Sponsored by Accel-Heal and editorial support provided by Jenny Smith, JMS Medical Writing Service Ltd.