Improving Diabetic Wound Healing Outcomes with Topical Growth Factor Therapies: Systematic Review and Network Meta-analysis of Randomised-controlled Trials.

Abstract

Diabetes mellitus is associated with morbid complications such as diabetic foot ulcers (DFUs) that may lead to amputations or mortality if not managed adequately. New adjunctive interventions to treat diabetic wounds include topical biologics and growth factors. This study aims to evaluate their efficacy in improving wound healing outcomes and safety. Comprehensive database searches of MEDLINE via PubMed, EMBASE and Cochrane performed from inception to December 2022. Three independent researchers selected the studies. Randomised-controlled trials that compared the use of a topical biologic growth factor-containing regimen to other biologics or standard of care (SOC) were included. This review followed PRISMA guidelines. Risk of bias analysis was performed using the Jadad scale. Network meta-analysis was performed. Treatments were grouped into common nodes based on the type of biologic agent. Primary outcomes of interest were healing rate and time to wound closure. Secondary outcomes included wound infection, serious adverse events, and amputation rate. Human umbilical cord (HUC) was associated with the highest cure, followed by recombinant human epidermal growth factor (hEGF). A significantly greater reduction in the time to cure DFUs was seen in HUC, hEGF and fibroblast growth factor (FGF). There was a significantly lower risk of adverse events (AEs) when platelet-rich plasma (PRP) was administered. HUC, hEGF and FGF are promising topical biologics with statistically significant primary outcomes compared to SOC, while PRP is effective in reducing ulcer-related AEs. HUC has been found to be the most effective in terms of cure rate and a reduction in time to cure.