Self-Powered Piezoelectric Nanofibrous Hydrogel for Synergistic Electro-Pharmacological Therapy of Chronic Wounds

Chronic wounds such as diabetic foot ulcers and burns pose clinical challenges due to persistent inflammation and impaired endogenous bioelectric signaling. Here, we report a self-powered piezoelectric nanofibrous hydrogel for synergistic electro-pharmacological therapy, fabricated via dual-nozzle electrospinning and Ca²⁺ crosslinking. This therapeutic paradigm facilitates a dual-action mechanism that integrates direct biophysical stimulation with electro-kinetically accelerated drug delivery, both driven autonomously by physiological motion. This platform integrates a β-phase-rich poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) matrix with an ion-crosslinked polyvinyl alcohol-sodium alginate (PVA-SA) hydrogel, successfully transforming a hydrophobic interface into a hydrophilic one and matching human skin's modulus (1.8-2.1 MPa). By encapsulating immunomodulator resveratrol (RSV) and bactericidal silver nanoparticles (Ag NPs), the dressing converts biomechanical energy into therapeutic bioelectric potentials (0.3-3.0 V). Mechanistically, the motion-induced piezoelectric field generates electro-kinetic driving forces that actively upregulate the transport rate constant (K) by reducing the energy barrier for molecular diffusion, thereby accelerating RSV bioavailability beyond passive diffusion. In a Staphylococcus aureus-infected chronic wound model, the synergy significantly facilitates wound closure (95.8% vs 63.3% by day 10) by effectively suppressing inflammation, promoting angiogenesis, and accelerating collagen maturation, with excellent biocompatibility and no systemic toxicity. This study establishes a scalable strategy for recalcitrant inflammatory injuries and motion-associated pathologies.