Abstract
Diabetic wound healing, characterized by persistent inflammation, impaired angiogenesis, and dysfunctional cellular responses, remains a major clinical challenge due to its complex pathophysiology. This challenge is most evident in diabetic foot ulcers (DFUs), which carry high risks of infection, recurrence, and amputation, contributing substantially to patient morbidity, mortality, and healthcare costs. Despite multidisciplinary care, debridement, and advanced dressings, healing outcomes are often suboptimal, highlighting an urgent need for deeper pathophysiological insights and more effective therapeutic strategies. This review synthesizes current understanding of DFU pathogenesis, emphasizing how sustained metabolic dysfunction disrupts fibroblast and immune cell function, thereby perpetuating chronic wounds. We also critically examine commonly used animal models and their limitations in replicating the complexity of human DFUs and discuss emerging therapeutic approaches with translational promise. Advancing our understanding of these mechanisms and validating innovative interventions may ultimately reduce DFU-related amputations and mortality, improve healing outcomes, and enhance patient quality of life. This review aims to catalyze future research and therapeutic innovation in diabetic wound care.