Dihydromyricetin-loaded nanofiber membranes accelerate diabetic wound repair via PI3K/AKT-mediated immune regulation

Dihydromyricetin-loaded membranes sustain local delivery in diabetic wounds. • The membranes reduce inflammation and promote fibroblast migration. • Repair is linked to phosphoinositide 3-kinase/protein kinase B signaling. • Treatment speeds wound closure, collagen deposition, and angiogenesis. Diabetic wounds remain a major clinical challenge because of persistent inflammation, impaired angiogenesis, and delayed tissue repair. Here, we developed a dihydromyricetin (DHM)-loaded polyvinylpyrrolidone/polyvinyl butyral electrospun nanofiber membrane (PBDEM) as a local therapeutic dressing for diabetic wound treatment. PBDEM improved DHM dispersion and local retention, enabled sustained release, and showed favorable biocompatibility. By integrating network pharmacology, GEO transcriptomic analysis, molecular docking, molecular dynamics simulation, and in vitro and in vivo validation, we identified PI3K/AKT signaling as a key pathway associated with PBDEM action. In vitro , PBDEM reduced high-glucose-induced pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), increased anti-inflammatory factors (TGF-β1 and IL-10), and promoted fibroblast migration. In diabetic mice, PBDEM alleviated early inflammation, accelerated wound closure, and enhanced collagen deposition and angiogenesis. These findings indicate that PBDEM is an active local drug-delivery platform that promotes diabetic wound healing through PI3K/AKT-associated immune regulation. Download: Download high-res image (146KB) Download: Download full-size image