Bioactive wound dressings for diabetic foot ulcers: mechanisms, materials, and clinical translation

Diabetic foot ulcers (DFUs) constitute a severe and formidable complication of diabetes, in which the healing process is hampered by neuropathy, vascular dysfunction, persistent inflammation, and oxidative stress. Conventional therapeutic approaches, such as debridement and negative pressure wound therapy, frequently fail to completely reinstate the healing cascade, thereby necessitating the development of advanced dressings capable of actively interacting with the wound microenvironment. This review systematically summarizes the recent advancements in DFU dressings, classifying them into traditional, natural polymer-based (chitosan, alginate, collagen), synthetic polymer-based (poly (lactic-co-glycolic acid), polyvinyl alcohol, polyethylene glycol), and multifunctional systems. A primary emphasis is placed on clarifying their mechanisms of action, especially in promoting angiogenesis, alleviating oxidative stress, facilitating the transition of macrophages from the pro-inflammatory M1 phenotype to the reparative M2 phenotype, and regulating crucial signaling pathways such as AMPK, Wnt/β-catenin, and Nrf2/ARE. Although the preclinical evidence for numerous bioactive dressings is promising, their clinical translation remains restricted, with only a few (e.g. collagen-based, silver-alginate dressings), currently approved for utilization. Future research endeavors should prioritize the development of multifunctional and responsive dressings, supported by rigorous clinical validation through standardized evaluation and large-scale trials. This review offers a comprehensive and critical synthesis of the current evidence, highlighting both mechanistic understandings and the existing disparities between laboratory research and clinical application in DFU dressing technology.