How Can A Biodegradable Matrix O er
Limb-Saving Options for Chronic Limb
Threatening Ischaemia?
Editorial Summary
Chronic limb-threatening ischaemia, marked by severely reduced blood ow, 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 neovascularization in limbs previously deemed unsalvageable.4 Findings suggest biodegradable temporising matrices (BTM), properly integrated with standard of care, can achieve signi cant wound closure and limb salvage.
Introduction
For wound specialists, chronic limb ischaemia is among our most recalcitrant diagnoses. This limb-threatening condition results from severe arterial blockages depriving tissues of su"cient perfusion for cell viability and healing. Critical limb ischaemia (CLI), now known as chronic limb-threatening ischaemia (CLTI), represents the most advanced state of peripheral arterial disease (PAD) and manifests as rest pain, non-healing ulcers, and/ or gangrene. 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 identi ed early in our clinical practice. 1-4
Table 1: Features of Chronic Limb-Threatening Ischaemia.
It is reported 10% of PAD patients may progress to develop CLTI, the most severe form of PAD. PAD itself is very common, a ecting over 200 million people worldwide, so this translates to a large number of patients at risk for CLTI. 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 Identi cation:
Identifying PAD patients who are progressing towards CLTI is crucial for preventing major limb amputation, disability, and death. Earlier diagnosis allows for more aggressive risk factor modi cation (e.g. smoking cessation, lipid and glycaemic control in diabetes) and treatment (e.g. revascularization procedures). Patients should also be placed on antiplatelet and statins for cardiovascular protection.
Gangrene
All clinicians should assess for PAD signs and symptoms like intermittent claudication, non-healing ulceration, absent pulses, and incorporate tools like the ankle-brachial index, or the use of toe pressures.
In summary, identifying these high-risk patients early is essential for improving outcomes and reducing the very high rates of readmission and complications. Increasing awareness of CLTI among clinicians across specialties who care for patients with vascular disease is an important priority. 1-3
Ms Victoria Bristow
Vascular Specialist Nurse, Cambridge University Hospitals Cambridge,
“Achieving adequate wound coverage and promoting healing in complex wounds remains a signi cant challenge in surgical practice. Biodegradable Temporising Matrix (BTM) is a synthetic dermal sca old that has gained increasing attention in recent years due to its unique properties and potential bene ts in wound healing. 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 signi cant challenge in surgical practice. NovoSorb® Biodegradable Temporising Matrix (BTM) (PolyNovo Biomaterials Pty Ltd., Port Melbourne, VIC, Australia) is a synthetic dermal sca old that has gained increasing attention in recent years by clinicians due to its unique properties and potential bene ts in wound healing. 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 sca old, 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 broblasts 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 wound
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 ndings suggest that BTM may o er advantages over traditional burn management techniques in select patient populations. 19
Applications in Reconstructive Surgery:
BTM has also been utilized in the management of reconstructive surgical procedures. In a retrospective review by Wagsta et al., BTM was used in the reconstruction of free ap donor sites in a variety of surgical procedures.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 o er bene ts in this patient population.21,22
“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 an increased length of stay 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 an increased length of stay and for some, loss of independent living. The matrix is initially placed over the defect to create a neodermis.
Below is a case of 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 polytetra uoroethylene (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.
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
“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 surgery including 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
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 2: Overview of the necrosis demarcation.
Figure 3: Fixation of BTM with staples after wound debridement
Figure 4: Overview of healing progression.
“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
Characterized by the triad of rest pain, nonhealing ulcers, and gangrene, CLTI results from severe arterial atherosclerotic disease, 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
Reconstructive Methods in CLTI
The management of CLTI involves a multidisciplinary approach, with the primary goal of restoring adequate perfusion to the a ected 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 runo 17
Additional Reconstructive Methods Include:
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 e ective in promoting wound closure, it requires a well-vascularized wound bed and may result in donor site morbidity and suboptimal cosmetic outcomes.
Local aps: Local aps involve mobilizing adjacent tissue to cover the wound defect. This technique can provide better cosmetic results and maintain sensation in the a ected area. However, local aps may not be feasible in patients with extensive tissue loss or compromised vascularity in the surrounding tissue. 16
Free aps: Free aps 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 sca old 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 sca old 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 e ectiveness 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
In the context of CLTI, BTM may o er 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 ap donor site, reducing the risk of donor site morbidity and improving patient comfort.4
How Can A Biodegradable Matrix
“In the context of CLTI, BTM may o er several advantages over traditional reconstructive methods. Firstly, BTM can be applied directly to the wound bed, even in the presence of exposed tendons, and bones providing a suitable environment for wound healing. Secondly, BTM does not require a separate ap donor site, reducing the risk of donor site morbidity and improving patient comfort.”
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 Wound Therapy (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, o ering a viable option when conventional revascularization techniques have failed.
By providing a temporary sca old 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 eld 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 thereby restoring the microcirculation o er glimmers of new hope and yet 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 bene ts/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.
How Can A Biodegradable Matrix O er 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.”
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