Abstract

A novel keratin-based wound dressing enriched with sodium acetate (FKDP+0.1%Act) was developed to address the constant challenges of chronic wound healing in diabetes. By combining bioactive keratin fibers with the anti-inflammatory properties of acetate, this study explored the material's regenerative and immunomodulatory potential using in vitro models of keratinocytes and macrophages, alongside full-thickness wounds in diabetic rats. FKDP+0.1%Act markedly accelerated wound closure and improved tissue architecture during early healing. It promoted a shift toward pro-regenerative M2 macrophage polarization, reduced M1-associated markers and tumor necrosis factor alpha (TNF alpha) expression, and significantly upregulated vascular endothelial growth factor (VEGF) and cytokeratins 16 and 17 (KRT16/17) - key angiogenesis and epidermal repair mediators. These effects were consistently observed across in vivo and in vitro methods, highlighting a synergistic interaction between keratin and acetate. The dressing preserved structural integrity, demonstrated favorable cytocompatibility, and modulated key inflammatory and regenerative pathways. These findings underscore the translational potential of FKDP+0.1%Act as a dual-functional biomaterial capable of enhancing epithelial regeneration and reprogramming inflammatory responses in impaired diabetic wound environments.