Systematic Review of Cellular, Acellular, and Matrix-like Products and Indirect Treatment Comparison Between Cellular/Acellular and Amniotic/Nonamniotic Grafts in the Management of Diabetic Foot Ulcers.

Significance: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant review focuses on the efficacy of cellular, acellular, and matrix-like products (CAMPs) in the management of diabetic foot ulcers (DFUs) based on published randomized controlled trials (RCTs). Recent Advances: Although CAMPs have been incorporated into the clinical algorithm for chronic wounds, evidence is lacking to comparatively evaluate the efficacy of these products. Critical Issues: Level 1 RCT studies are the gold standard to evaluate the efficacy of different treatment approaches; however, due to differences in surgical techniques, patient demographics, and compliance, standard-of-care (SOC) outcomes in the wound care space can vary significantly between different RCTs, making it difficult to compare them against each other. Future Directions: To mitigate variability between different RCTs, wound closure outcomes can be reported as risk ratios (RRs). This review of all the currently published RCTs (with a similar trial design) in patients with DFU and RRs confirms that CAMPs adjunct to SOC result in statistically superior wound closure outcomes in DFUs, when compared with SOC alone, with a RR of 1.72 [1.56, 1.90], p < 0.00001. Enough evidence is still lacking to determine a statistical difference between broad categories of cellular/acellular and amniotic/nonamniotic CAMPs, and hence, decision makers should consider published head-to-head comparative studies, real-world evidence, and cost-effectiveness evidence between individual CAMPs to decide on which to use in practice.