Advanced Biomaterials and Topical Medications for Treating Diabetic Foot Ulcers: A Systematic Review and Network Meta-Analysis.

Significance: With the increasing diabetic population worldwide, diabetic foot ulcers (DFUs) are a significant concern. This study aimed to compare the efficacy of skin substitutes, biomaterials, and topical agents with standard care. Recent Advances: A meta-analysis was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, EMBASE, and Web of Science were searched using the following keywords: diabetes mellitus AND skin graft OR tissue replacement OR dressing OR drug. Two independent reviewers performed data collection and quality assessment of the eligible studies. The primary outcome was the 12- to 16-week healing rates and the secondary outcome was recurrence rates. Critical Issues: Thirty-eight randomized controlled trials, including 3,862 patients, were analyzed. The studies exhibited low heterogeneity (τ2 = 0.10) without significant asymmetry (Egger's test, p = 0.8852). After pooling direct and indirect estimates, placenta-based tissue products exhibited the best wound healing probability (p-score = 0.90), followed by skin substitutes with living cells (p-score = 0.70), acellular skin substitutes (p-score = 0.56), and advanced topical dressings (p-score = 0.34) compared with standard of care. The recurrence analysis showed significant improvement in the intervention group compared with the control group (11.21% vs. 15.15%). Future Directions: This network meta-analysis provides the relative effectiveness and rank of biomaterials and topical dressings in DFU healing. The results could help clinical decision making.