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

Diabetic foot ulcers (DFU) represent a severe and challenging complication of diabetes, where healing is impaired by neuropathy, vascular dysfunction, persistent inflammation, and oxidative stress. Conventional therapies, including debridement and negative pressure wound therapy, often fail to fully restore the healing cascade, creating a need for advanced dressings that can actively interact with the wound microenvironment. This review systematically summarizes recent progress in DFU dressings, categorizing them into traditional, natural polymer-based (chitosan, alginate, collagen), synthetic polymer-based (PLGA, PVA, PEG), and multifunctional systems. A key focus is placed on elucidating their mechanisms of action, particularly in promoting angiogenesis, reducing oxidative stress, facilitating the transition of macrophages from proinflammatory M1 to reparative M2 phenotypes, and regulating critical signaling pathways such as AMPK, Wnt/β-catenin, and Nrf2/ARE. While preclinical evidence for many bioactive dressings is promising, their clinical translation remains limited, with only a few (e.g., collagen-based, silveralginate dressings) currently approved for use. Future research directions should prioritize the development of multifunctional and responsive dressings, underpinned by robust clinical validation through standardized evaluation and large-scale trials. This review provides a comprehensive and critical synthesis of current evidence, highlighting both mechanistic insights and the existing gaps between laboratory research and clinical application in DFU dressing technology.