Does the Gender of Cellular and/or Tissue-Based Products (CTPs) affect Wound Healing Outcomes in an Outpatient Center Meaghan
1 Coles ,
1Donald
Christina Del Pin,
2, MD Amit
Rao,
and Barbara Zucker School of Medicine at Hofstra/Northwell 2Comprehensive Wound Care Center at North Shore University Hospital
Results
Background An estimated 9 to 12 million Americans suffer from chronic 1 wounds . The annual cost of care for these wounds was upwards of 28 billion dollars 1. Chronic wounds are seen across all age groups and in patients with numerous comorbidities that delay wound healing (e.g. ESRD, DM, immune suppression). Bioengineered skin substitutes provide means of temporary wound closure that provides a template for the patient’s own cells to grow 4. Previous research has shown that wound healing varies amongst men and women receiving skin substitutes from 5 male versus female sourced tissues . Grafix ™ (FCTP) is derived from cryopreserved placental membranes, which are biologically female2. Apligraft ™ (MCTP) is derived from the keratinocytes of male foreskin3.
Objective
Our goal is to determine the effect of the gender of cellular and/or tissue based products on wound healing outcomes. Understanding these differences will help to inform proper standard of care of chronic wounds.
Methods
Sample Size (n,%) Diabetes Mellitus (n,%)
Results
M w/ FCTP F w/ MCTP M w/ MCTP F w/ FCTP Men who received MCTPs had significantly higher rates of HBO utilization than men who received FCTPs or women who 9 (9.8) 27, (29) 44 (48) 12 (13)
5 (56)
13 (48)
21 (48)
3 (25)
Anticoagulation (n,%) 5 (56)
3 (33) 3 (33)
15 (56) 5 (19) 4 (15)
20 (46) 9 (21) 9 (20)
8 (67) 3 (25) 5 (42)
1 (11) 77.89 2.5
0 (0) 73.54 2.5
9 (21)* 59.25* 3.1*
2 (17) 72.58 2.5
ARBs (n,%) ImmunoCompromised (n,%) HBO Therapy (n,%) Average Age (yrs) Average BMI
2, MD
Table 1: Demographic data stratified by gender and type of CTP used. The prevalence of DM, AC, ARBs, and immunosuppression were similar amongst all groups. Hyperbaric oxygen (HBO) therapy was used at a higher frequency in men receiving MCTPs than any other group (p= 0.007).Men receiving MCTPs has a lower average age and had a higher average BMI class than the other groups. Figure 1: Wound Healing 1 Month Post-Application. This figure shows the percentage of cases in each group who achieved 50% wound closure 1 month after application of the final skin substitute. Both genders appear to have higher healing rates when receiving CTPs correlating with their biologic gender.
This project is an IRB approved retrospective study. The population studied includes cases recorded in the AllScripts EMR between 2016 and 2020 who have received a CTP at the Northwell Comprehensive Wound Care Center. Aplligraft™ (MCTP) and Grafix ™ (FCTP) are the products focused on in this study. The wounds were classified as venous, arterial, or other, which references both traumatic and surgical. Venous and arterial 1 Month 3 Months Average Dose wounds were also further classified as pre- intervention and post4 2.1 intervention, which includes ablation and angioplasty. Variables M w/FCTP (n) 3 reviewed include age, BMI, presence of diabetes mellitus, use of FFigure Independent CRISPR w/7: MCTP (n)knockout 13of CDK4 or CDK6 16 2.59 does not cause dropout in most breast cancer cell lines studied. ARBs, anticoagulation, immunosuppression, use of HBO, dose of M w/ MCTP (n) 33 * 38 2.46 CTP, and 50% wound size reduction. Descriptive statistics include F w/ FCTP (n) 8 6 1.83 averages and chi-square analysis with Microsoft Excel. This Table 2: Outcomes of wound healing stratified by gender and intervention. At 1 month preliminary data includes 50% of all eligible cases from the post-application, men receiving MCTP were significantly more likely to be 50% healed database (A-L). A sample size of convenience was used and no (p=0.006). At 3 month post-application, there was no longer a significant difference in the healing rates between groups (p=0.06) formal power calculation was conducted.
received MCTPs or FCTPs (p = 0.007). Men who received MCTPs has a significantly lower average age and were in a higher average BMI class. There were no significant differences in the other demographics, including race, when comparing between groups (Table 1). Men who received MCTPs were significantly more likely to have have wound size reduction ≥50% (p = 0.006) than other groups 1 months post-application (Table 2). Wound size reduction ≥50% 3 months post-application was similar (p= 0.06) amongst all groups (Table 2).
Conclusions One month post skin-substitute application, there is a difference in chronic wound healing when making comparisons between the gender of the patient and the biological gender of the skin substitute applied. Males receiving Apligraft ™ had significantly higher rates of wound size reduction. This finding may be a result of a higher rate of utilization of hyperbaric oxygen therapy during treatment or the younger average age of males receiving MCTPs. HBO therapy increases oxygenation levels at wound sites and provides favorable conditions for wound healing. Older age leads to cellular senescence of dermal fibroblasts and other cell types, which impairs the healing process. Three months after the final skin substitute has been applied the protective factor for men receiving MCTPs is lost. Increasing the sample size of the study will help to reduce biases amongst these groups and will allow for cohorts with more similar demographics (e.g. age, BMI, HBO therapy) to be formed.
References 1. 2. 3. 4. 5.
Sen, Chandan K. “Human Wounds and Its Burden: An Updated Compendium of Estimates.” Advances in Wound Care, vol. 8, no. 2, 13 Feb. 2019, pp. 39–48., https://doi.org/10.1089/wound.2019.0946. Accessed 26 Sept. 2021. Grafix PL membrane and Grafix◊ cryopreserved placental membrane. GRAFIX. (n.d.). Retrieved September 27, 2021, from https://www.grafixpl.com/?gclid=Cj0KCQjwtMCKBhDAARIsAG-2Eu-d7TNoMMTWthB2oB1AgXG7GKrxwOPov0mEV7pg5ycUcb5mgnXwNcaAgw-EALw_wcB. “Apligraft Living Cellular Skin Substitutes .” Apligraf, https://apligraf.com/. Nicholas, Mathew N., and Jensen Yeung. “Current Status and Future of Skin Substitutes for Chronic Wound Healing.” Journal of Cutaneous Medicine and Surgery, vol. 21, no. 1, 2016, pp. 23–30., https://doi.org/10.1177/1203475416664037.