Comparative Outcomes Amniotic Tissue Membrane Versus Standard Care in Diabetic Foot Ulcer Management: A Real-World Retrospective Cohort Study

Published October 30, 2025

Executive Summary

Diabetic foot ulcers represent a persistent clinical and economic challenge due to their chronic nature, high recurrence rates, and multifactorial etiology. These wounds significantly impair patient quality of life and place a substantial burden on healthcare systems through prolonged and costly treatment regimens. Despite the availability of standard and advanced therapeutic options—including compression therapy, wound dressings, biologics, and mechanical devices—idiopathic cases often remain resistant to healing, underscoring the need for innovative treatment strategies.

This clinical study explored the use of Membrane Wrap™, a human tissue allograft derived from the amniotic membrane, as a novel therapeutic intervention for DFUs via the collection of real-world data (RWD). Regulated by the FDA under 21 CFR Part 1271 as a Human Cellular and Tissue-Based Product (HCT/P), Membrane Wrap™ is designed to serve as a protective wound covering. Its application is indicated for use in DFUs in conjunction with standard care protocols, including exudate management, debridement and offloading.

The study aimed to evaluate clinical outcomes associated with Membrane Wrap™ treatment compared to standard of care therapies alone in a real-world setting. By advancing the understanding and application of membrane technologies in chronic wound care, this research sought to contribute to a paradigm shift in the management of DFUs.

Study Overview

Design:

Multicenter, retrospective cohort study evaluating the effectiveness of human amniotic tissue membrane (ATM) (Membrane Wrap™) versus standard of care (SOC) in treating chronic diabetic foot ulcers (DFUs).

Ethics:

This study was conducted under a waiver of informed consent and HIPAA authorization granted by Sterling Institutional Review Board #13631 on April 23, 2025. All data were de-identified and handled in accordance with ethical standards and data protection regulations.

Sites & Subjects:

Clinical data for participants receiving either ATM + SOC or SOC alone were extracted from the U.S. Wound Registry (USWR), a national repository of research-grade wound care data (Intellicure, LLC, The Woodlands, TX). Participants in the SOC arm were matched to ATM-treated patients using propensity score methods based on wound type, wound size, and comorbidities. The study period extended from January 2022 through October 2025.

Objective:

To assess wound closure rates and healing outcomes using amniotic tissue membranes in combination with SOC compared to SOC alone.

Methods

1. Study Population

Inclusion Criteria:

Adults ≥18 years with diabetes (Type 1 or Type 2)
Treated with Membrane Wrap™ plus SOC or SOC alone
Treatment between January 1, 2022 and June 30, 2025
DFUs >2cm²in area

Exclusion Criteria:

No follow-up wound assessment
Use of other wound care agents

2. Treatment Arms

ATM + SOC Group: Received Membrane Wrap™ plus SOC
SOC-Only Group: Received SOC alone (may include adjunctive therapies such as hyperbaric oxygen and negative pressure wound therapy)

3. Data Collection

De-identified EMR data included:

Demographics (age, sex, BMI, race)
Medical/wound history
Ulcer characteristics
Treatment details

4. Propensity Score Matching

Deidentified electronic health record (EHR) data were extracted from the Intellicure database spanning February 15, 2017, to June 30, 2025. Data quality was ensured through manual validation, with outliers and missing values retained to support robustness. Subjects were categorized into treatment (Membrane Wrap™) and control (no cellular/tissue-based products) groups. Patients lacking outcome data due to loss to follow-up, death, or transfer were excluded.

Diabetic patients with foot pressure ulcers were reclassified as having diabetic foot ulcers (DFUs). Wound location was determined using descriptive entries and ICD-10 codes (primarily L89.6). The most severe tissue exposure per wound was identified across visits. Small wounds were retained due to their negligible impact.

Outcomes were classified as “Healed,” “Healing,” or “Worsening” based on standardized wound size change rate (r). Specifically, wounds with final size ≤0.5 cm² and r ≤ −0.0001 were labeled “Healed”; those with r ≥ 0.0001 as “Worsening”; others as “Healing.”

Matching was performed at the wound level using 16 factors encompassing demographics, clinic characteristics, comorbidities, and wound attributes. A 1:1 nearest neighbor match based on Mahalanobis distance was applied (R v4.5.1, MatchIt v4.7.2). Descriptive statistics summarized matched pairs and signed rank tests assessed outcome differences. A Type I error rate of 0.05 was maintained throughout.

Endpoints

Primary Endpoint:

Complete wound closure by week 16, defined as full epithelialization without drainage

Secondary Endpoints:

Reduction in wound area/depth
Appearance of granulation tissue

Results Summary

Patient and Wound Demographics

A total of 85 patients with 92 wounds were included in the matched cohort analysis. The mean age was slightly higher in the Membrane Wrap™ group (73.83 ± 9.85 years) compared to the standard care group (71.93 ± 9.52 years), though not statistically significant (p = 0.0622). The majority of patients in both groups were over 65 years of age (84.8% vs. 80.4%, p = 0.7237), and predominantly male (78.3% vs. 80.4%, p = 1.0000).

Race data were incomplete, with substantial missingness (41 in 46 in the Membrane Wrap™ group, 12 of 46 in the SOC group). Among available data, most patients identified as White (80.0% in Membrane Wrap™, 76.5% in standard care). BMI was similar between groups (29.07 ± 4.05 vs. 31.19 ± 8.14, p = 1.0000), though BMI data were missing for the majority of Membrane Wrap™ patients.

Arrival methods were comparable, with ambulatory status being the most common (50.0% vs. 47.8%). Wound age at first treatment was significantly longer in the Membrane Wrap™ group (181.59 ± 132.99 days) than in the standard care group (130.59 ± 142.30 days, p = 0.0040).

All patients had diabetes. Comorbidities such as peripheral artery disease, chronic kidney disease, congestive heart failure, dementia, autoimmune disease, paralysis, and malnourishment were similarly distributed across groups, with no statistically significant differences.

The number of concomitant wounds varied, with most patients having one or two wounds. A higher proportion of Membrane Wrap™ patients had four wounds (13.0% vs. 4.3%), while more standard care patients had three wounds (19.6% vs. 6.5%).

Wound Healing

A total of 92 diabetic foot ulcers (DFUs) were analyzed, with 46 wounds in each of the Membrane Wrap™ and SOC groups. Wound location was predominantly heel and midfoot in both groups (78.3% vs. 84.8%), with minor representation from other foot regions. Tissue exposure was similar across groups, with subcutaneous tissue being the most common (73.9%).

Wounds in the Membrane Wrap™ group had significantly longer wound duration (181.6 ± 133.0 days vs. 130.6 ± 142.3 days, p = 0.0040) compared to the SOC group. The MW treated wounds were significantly larger in wound size compared to the SOC group (13.5 ± 20.0 cm² vs. 11.3 ± 20.6 cm², p = 0.0224).

Granulation tissue coverage was more favorable in the Membrane Wrap™ group, with 56.5% of wounds having granulation tissue compared to 30.6% in the control group. Wound size reduction was comparable (−0.42 ± 0.53 vs. −0.31 ± 0.89, p = 0.9952).

Primary Endpoint:

Complete wound closure by week 16 was not formally reported due to variability in follow-up timing across the retrospective cohort.

Clinical outcomes indicated a higher proportion of healing or healed wounds in the Membrane Wrap™ group (84.8% vs. 76.1%), though not statistically significant (p = 0.2497).

Discussion

This retrospective analysis examined real-world outcomes associated with Membrane Wrap™ treatment compared to SOC in DFUs. Although most comparisons did not achieve statistical significance. The findings revealed directional trends favoring Membrane Wrap™ treatment.

Healing or healed outcomes were numerically more frequent in the Membrane Wrap™ group (84.8%) compared to standard care (76.1%). A greater proportion of wounds exhibited >50% granulation tissue coverage in the Membrane Wrap™ group (56.5% vs. 30.6%), suggesting enhanced wound bed preparation, though statistical testing for this comparison was not reported.

Notably, Membrane Wrap™ was applied to wounds with significantly longer baseline duration (181.6 vs. 130.6 days, p = 0.0040) and larger baseline size (13.5 vs. 11.3 cm², p = 0.0224). These baseline imbalances favor the control group, as both chronicity and size are negative prognostic factors.

The observed baseline imbalances also warrant particular consideration when interpreting outcomes. Wounds with longer duration and larger size require greater clinical resources and extended timeframes to achieve healing. These wound characteristics suggest that clinicians may have preferentially selected Membrane Wrap for more complex cases that met criteria for advanced wound intervention. The comparable outcomes achieved despite these prognostic disadvantages in the Membrane Wrap™ group provide preliminary signal of potential benefit, though additional research is required to confirm these preliminary findings.

Conclusion

This retrospective analysis observed directional trends suggesting potential benefits associated with Membrane Wrap™ treatment in DFUs, including numerically higher rates of healing or healed wounds and greater granulation tissue coverage. Given methodological constraints inherent to retrospective observational studies, further research is needed to confirm these findings.

Study Limitations

This retrospective analysis has several important limitations that must be considered when interpreting the findings:
Study Design and Methodology
As a retrospective observational study, this analysis is subject to inherent limitations in the study model. The small sample size (46 wounds per group) may have been insufficient to detect statistically significant differences between treatment groups.
Data Characteristics
Substantial missing data for key demographic and clinical variables limits the comprehensiveness of the analysis. Additionally, baseline imbalances persisted between groups despite propensity score matching, with the Membrane Wrap™ group having significantly longer wound duration and larger baseline wound size. Both wound chronicity and increased size are established negative prognostic factors associated with reduced healing rates and greater resource requirements. These imbalances limit the ability to draw definitive conclusions about treatment efficacy from this observational comparison.
Treatment Variables
Registry data did not systematically capture important treatment variables including re-vascularization procedures, off-loading protocols, and wound bed preparation techniques.
Study Funding
This analysis was funded by Biolab Holdings, manufacturers of Membrane Wrap™.

Given these limitations, the findings should be considered hypothesis-generating. Future prospective studies with improved methodological rigor, including randomized controlled trials, are needed to definitively establish clinical efficacy.

Disclosures

Publication Type:
This analysis has undergone peer review and appears as an industry-sponsored case study report.
Intended Use:
This report is intended for educational purposes. The findings represent observational data from a retrospective analysis and should not be interpreted as establishing causality or clinical superiority.
Author Disclosures:
Marshal Medley, DO, FACOS, CWSP serves as Chief Medical Officer of Biolab Holdings. Carlos Encinas, PhD serves as Chief Science Officer of Biolab Holdings. Windy Cole, DPM, CWSP has received consulting fees from Biolab Holdings.
Funding and Sponsorship:
This retrospective analysis was funded solely by Biolab Holdings (Protocol Number: RWE-001-24).

References

References are listed include peer-reviewed studies on DFUs, wound care standards, and biologic therapies.

Nussbaum SR, Carter MJ, Fife CE, et al. An economic evaluation of the impact, cost, and Medicare policy implications of chronic nonhealing wounds.Value Health 2018;21:27- 32.
Driver VR, Fabbi M, Lavery LA, et al. The costs of diabetic foot: the economic case for the limb salvage team. J Am Podiatr Med Assoc 2010;100:335-41.
Chan B, Cadarette S, Wodchis W, et al. Cost-of-illness studies in chronic ulcers: a systematic review. J Wound Care 2017;26(Suppl 4):S4–S14.
Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot ulcers receiving standard treatment. A meta-analysis Diabetes Care 1999;22:692-54.
Mauricio D, Piaggesi A, Ragnarson Tennvall G, et al. Predictors of lower-extremity amputation in subjects with an infected diabetic foot ulcer. Diabetes Care 2015;38:852-7.
Ansari P, Akther S, Khan JT, Islam SS, Masud MSR, Rahman A, Seidel V, Abdel-Wahab YHA. Hyperglycaemia-Linked Diabetic Foot Complications and Their Management Using Conventional and Alternative Therapies. Applied Sciences. 2022; 12(22):11777. https://doi.org/10.3390/app122211777.
Haugh AM, Witt JG, Hauch A, Darden M, Parker G, Ellsworth WA, Buell JF. Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis. Plast Reconstr Surg Glob Open. 2017 Apr 25;5(4):e1302. doi: 10.1097/GOX.0000000000001302. PMID: 28507863; PMCID: PMC5426882.

Study Authors
Windy Cole DPM, CWSP, Lead Principle Investigator
Marshall Medley, DO, FACOS, CWSP, Chief Medical Officer, Biolab Holdings
Carlos Encinas, PhD, Chief Science Officer, Biolab Holdings

Estimated Time

Comparative Outcomes Amniotic Tissue Membrane Versus Standard Care in Diabetic Foot Ulcer Management: A Real-World Retrospective Cohort Study

Executive Summary