Efficacy of a Polylactic Acid Matrix for the Closure of Wagner Grade 1 and 2 Diabetic Foot Ulcers: A Single-center, Prospective Randomized Trial

DFUs are a major health care issue due to their high prevalence, complications, and economic burden.¹ Up to 12.5% to 14% of individuals with diabetes will develop a foot ulcer during their lifetime, and these ulcers are responsible for a large number of hospital admissions. Furthermore, DFUs are a leading cause of non-traumatic amputations, as a nonhealing DFU precedes most amputations.^2,3 Thus, treating DFUs is complex and requires a multidisciplinary approach involving wound care, infection control, offloading pressure, and addressing any underlying issues.⁴ DFUs that fail to respond to conventional therapies will often require advanced materials, such as CAMPs, to aid in their healing.⁵ PLA is a synthetic CAMP that has demonstrated exceptional outcomes in healing burns, acute wounds, and venous ulcers.^6-8 Therefore, the objective of this pilot trial was to compare the effectiveness of PLA closure matrices versus collagen dressings for promoting the closure of DFUs.

This was a prospective, randomized controlled trial of patients with single DFUs in one treatment center in Ohio, United States. The methodology was reviewed and approved by Advarra Institutional Review Board (Protocol Number: 056785) and conducted in compliance with US Food and Drug Administration standards and the ethical guidelines of the Declaration of Helsinki. The trial was registered with ClinicalTrials.gov (NCT05883098).

Inclusion criteria included a single Wagner grade 1 or 2 DFU with a duration of 12 weeks to 12 months and a size of 1 cm² to 25 cm². Patients were required to have an HbA_1c less than 10% and an ABI between 0.7 and 1.3 within 2 months of randomization. Offloading of the ulcer for a minimum of 14 days before randomization with a size reduction of less than 20% was also required. Exclusion criteria included active wound infections, gross edema, uncontrolled comorbidities, or the use of drugs that would modify wound healing. Elimination criteria included the development of infections requiring systemic antibiotics and the loss to follow-up for 2 or more consecutive visits.

After informed consent was obtained, participants underwent a 14-day pretreatment period consisting of the SOC: weekly debridement, wound care, and DFU offloading with a walking boot. Afterwards, patients were randomized to receive weekly applications of a PLA closure matrix (Supra SDRM, PolyMedics Innovations) plus SOC or collagen dressings (Fibracol Plus, 3M) plus SOC. Baseline data were obtained after the 14-day pretreatment period and every week afterwards until complete closure was achieved. Regardless of treatment arm, after debridement and preparation of the wound bed, the CAMPs were secured with a nonadherent dressing (Rylon-1, Biomed Sciences) and an outer layer of a superabsorbent dressing (DryMax Extra, MPM Medical). Compressive bandages were used to secure the materials in place.

The primary outcome was the time to achieve full healing, defined as complete (100%) wound reepithelialization without drainage and/or the need for a dressing. The secondary outcome was the proportion of ulcers healed at 12 weeks. Digital planimetry and estimation of the ulcers’ area were automatically calculated using a digital wound management system (Swift Skin and Wound app, Swift Medical).⁹

Continuous data are presented as either mean and standard deviation or median and IQR. Discrete data are presented as proportions. Wilcoxon rank-sum tests, Fisher exact tests, and Gray’s competing risk models were used to analyze the data by a researcher blinded to the treatment at the 95% CI using the statistical software R v.4.0.2 (The R Core Team, 2022). Because this was a pilot study, its sample size was not calculated a priori, and its results will be used for any future sample size calculations.

A total of 30 patients (15 per arm) were included in the study. Their characteristics are presented in Table 1. Baseline wound characteristics are presented in Table 2. No patients were eliminated from the trial.

The median time to achieve full healing was 9.3 ± 2.9 weeks in the PLA group versus 14.8 ± 8.1 weeks in the collagen group (P = .021) (Figures 1, 2). Twelve patients (80%) treated with PLA matrices achieved complete healing by week 12 compared to 5 patients (33%) (P = .025) in the collagen group. The OR of achieving full closure by 12 weeks with PLA was 2.23 (95% CI, 1.37–4.54). The competing risk and cumulative incidence for achieving full closure by 12 weeks with PLA matrices was 90% (95% CI, 37–99%) (Figure 3). 

All patients completed the trial, and no complications or adverse events were recorded.

Through the release of lactide into the wound bed and its breakdown to lactate, PLA has demonstrated several benefits, including increased angiogenesis, increased cell survival and proliferation, reduction in the inflammatory environment, and increased epithelization.^10-15 In the current study, the authors demonstrated a 44% reduction in time to healing for DFUs when treated with PLA matrices compared to collagen dressings. Furthermore, the results also demonstrated increased odds of attaining full closure by 12 weeks.

The wounds treated with PLA qualitatively showed increased granulation tissue content, thicker epithelial borders, and minimal scarring after healing. These findings suggest the increased healing rate is matched with the deposition of better tissue quality, but more studies are required to confirm this. 

The major limitation of this study is its sample size. Additional shortcomings include a lack of representativity of a diverse population due to the study’s setting, and the lack of masking of the patient and assessor. However, the latter pitfall was addressed using automated area calculation methods and blindly analyzing the data.

The results of the current study show PLA matrices induce a potent healing response that leads to reduced healing time and an increased OR for achieving healing by 12 weeks compared to collagen dressings.