Evidence for Healing Diabetic Foot Ulcers With Biologic Skin Substitutes: A Systematic Review and Meta-Analysis

Development of diabetic foot ulcers is a common complication of diabetes. Standard-of-care (SOC) therapy alone is often not sufficient to heal these wounds, resulting in application of adjuvant wound therapies including biologic skin substitutes. Although a variety of products exist, it has been difficult to formulate conclusions on their clinical efficacy. We therefore performed a systematic review and meta-analysis on the efficacy of healing diabetic foot ulcers with biologic skin substitutes.

A systematic review was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Four electronic databases (PubMed/MEDLINE, EMBASE [Ovid], Cochrane CENTRAL [Ovid], and Web of Science) were searched from inception through February 27, 2019. Searches included keywords and subject headings pertaining to 3 main concepts: biologic skin substitutes, wound healing, and diabetic foot ulcers. Cochrane randomized controlled trial filters were used to narrow results. Data were extracted from 54 included articles, and risk-of-bias assessments were conducted by 2 independent reviewers. The primary objective was to calculate a pooled risk ratio for the proportion of wounds completely closed by 12 weeks. Secondary objectives included a pooled risk ratio for the proportion of wounds completely closed by 6 weeks and mean time to healing.

Twenty-five studies were identified that assessed the proportion of complete wound closure by 12 weeks. We found that wounds treated with biologic dressings were 1.67 times more likely to heal by 12 weeks than those treated with SOC dressings (P < 0.00001). Five studies assessed the proportion of complete wound closure by 6 weeks. Wounds treated with biologic dressings were 2.81 times more likely to heal by 6 weeks than those treated with SOC dressings (P = 0.0001). Descriptively, 29 of 31 studies that assessed time to healing favored biologic dressings over SOC dressings.

This systematic review provides supporting evidence that biologic skin substitutes are more effective than SOC dressings at healing diabetic foot ulcers by 12 weeks. Future studies must address the relative benefits of different skin substitutes as well as the long-term implications of these products and their financial considerations.