Protocols, Clinical Effects, and Safety of Platelet-Rich Plasma for Diabetes-Related Foot Ulcers: A Systematic Review with Narrative Synthesis

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Abstract
Introduction. Platelet-rich plasma (PRP) has been investigated as an adjunctive therapy for diabetes-related foot ulcers, but heterogeneity in preparation and application protocols limits interpretation of the evidence. This review aimed to analyze current evidence on PRP, focusing on protocols, clinical effects, safety, and standardization gaps. Methods. This systematic review with narrative synthesis followed PRISMA 2020, the Cochrane Handbook, and SWiM guidance. Searches were conducted between September and October 2025 in MEDLINE/PubMed, LILACS, BDENF, CUMED, the Cochrane Library, Web of Science, and Scopus. Primary human studies published from 2021 to 2025 evaluating PRP or related platelet-derived products were included. Two reviewers independently screened studies and extracted data. Meta-analysis was not performed because of substantial clinical and methodological heterogeneity. Results. Of 907 records identified, 34 studies involving 3,597 participants were included. PRP was administered through different modalities, including dressings, gels, topical applications, injections, platelet-rich fibrin, and combinations with other wound-care technologies. Some studies reported favorable findings for complete ulcer closure, wound area or volume reduction, shorter healing time, granulation, re-epithelialization, and fewer local complications. Complete healing rates ranged from 55.3% to 95%, while healing time was most often between four and 16 weeks. However, methodological heterogeneity, moderate methodological quality, risk-of-bias concerns, and incomplete safety reporting limited interpretation of the findings. Discussion. PRP showed potential as an adjunctive treatment for diabetes-related foot ulcers, with favorable findings for tissue regeneration and wound healing in several studies. Its minimally invasive nature and relatively simple application may support clinical feasibility. However, heterogeneity among protocols, risk of bias, and incomplete safety reporting preclude definitive conclusions regarding its clinical effectiveness and safety.

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