A molecular perspective on diabetic wound healing: Exploring key signaling pathways.

Diabetic wounds are a serious healthcare concern, affecting approximately 25% of individuals with diabetes globally. Their healing process is often delayed by chronic hyperglycemia, oxidative stress, and persistent inflammation, all of which disrupt normal tissue repair. This review explores the molecular signaling pathways involved in diabetic wound healing and discusses emerging therapeutic strategies targeting these pathways. Key signaling routes such as Wnt/β-catenin, MAPK/ERK, NF-κB/NLRP3, Hippo-YAP, HIF-1α/VEGF-SDF-1α, AKT/eNOS, PI3K/Akt, Nrf2, TGF-β/Smad, and Notch are analyzed for their roles in cell growth, new blood vessel formation, inflammation reduction, and extracellular matrix remodeling. Diabetes disrupts these pathways through advanced glycation end-products, reactive oxygen species, and persistent inflammation, which impair keratinocyte migration, decrease angiogenesis, and prolong inflammation. Recently, promising therapeutic strategies have included nanoparticle-based pathway activation, exosome therapies, and bioactive compounds. Given the extensive interactions among these signaling pathways, therapeutic approaches should target multiple pathways rather than individual signaling components. Future therapeutic strategies may increasingly emphasize personalized medicine, leveraging AI-assisted diagnostics and customised combination therapies to improve management of chronic diabetic wounds.