From Hypoxia to Healing: Topical Deferoxamine Enhances Wound Closure and Neovascularization in Diabetic Animal Models - A Systematic Review and Meta-Analysis.

Abstract

Chronic wounds are a major health burden, affecting approximately 0.22% of the global population. Diabetic foot ulcers are particularly common and serious, due to their high risks of infection, amputation, and recurrence. Deferoxamine (DFO), an iron chelator that stabilizes hypoxia-inducible factor signaling and promotes angiogenesis, has been studied as a topical therapy to improve diabetic wound repair in preclinical studies. This systematic review and meta-analysis evaluates topical DFO in diabetic rat and mouse wound models. Following PRISMA guidelines and prospective PROSPERO registration, MEDLINE (PubMed), Embase, and Web of Science were systematically searched in November 2025. Internal validity was evaluated using the SYRCLE risk-of-bias tool. The primary endpoint was wound closure rate (%), and the secondary endpoint was neovascularization assessed by immunohistochemical quantification of CD31-positive vessels. Thirty-eight studies were included in the systematic review, and 29 provided sufficient data for meta-analysis. Topical DFO significantly improved wound closure (MD 13.26%, 95% CI 10.70-15.83) and increased neovascularization (SMD 2.39, 95% CI 1.64-3.14) compared to DFO-free controls (both p < 0.0001). Benefits were observed across diverse experimental settings and delivery systems. Subgroup findings further suggest that sustained local DFO availability may enhance efficacy. Topical DFO therapy demonstrates robust preclinical evidence for improving diabetic wound healing, supporting clinical translation. Future work should prioritize developing delivery platforms that enable controlled, prolonged local DFO exposure to maximize therapeutic benefit for patients with chronic wounds, especially those with diabetes.