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

ABSTRACT 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 Ca 2+ 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.