An Ultrasound‐Responsive Hydrogel for Diabetic Wound Electrotherapy Based on Interfacial Ion/Electron Transfer

Abstract Chronic diabetic wounds persist as a clinical healthcare challenge. In the hyperglycemic pathological milieu, excessive inflammation, peripheral neuropathy, and vascular disorders impede diabetic wound healing. Immunoregulation is substantially emphasized among these factors; however, research on neurovascular regeneration remains insufficient. Endogenous electric fields (EFs) can regulate cellular behaviors and significantly impact the wound healing process. Herein, a conductive composite hydrogel (CGGP) with ultrasound‐responsive electrical stimulation based on interfacial ion/electron transfer for diabetic wound electrotherapy is proposed. CGGP is synthesized through physicochemical crosslinking of gelatin and polyvinyl alcohol (PVA) dual networks and incorporated with curcumin‐loaded reduced graphene oxide (rGO). The conductivity of CGGP is comparable to that of skin. Notably, CGGP can generate electrical stimulation based on ion transfer at the fluid–solid interface (electrokinetic effects) and electron transfer at the curcumin‐rGO interface in response to ultrasound. Moreover, CGGP exhibits an ultrasound‐responsive release of curcumin for anti‐inflammatory treatment. The ultrasound‐responsive CGGP can promote the secretion of neurotrophic factors, vessel formation, and fibroblast migration. Furthermore, it facilitates local nerve regeneration, angiogenesis, and matrix remodeling in diabetic rat models, thereby accelerating diabetic wound healing. The sonoelectrical CGGP composite hydrogel holds great potential as a promising material for diabetic wound treatment.