Wireless Thermoelectric Hydrogel Recreates Biomimetic Electric Field and Angiogenic Signal Accelerating Diabetic Ulcer Repair

Abstract Endogenous electric field (EF)‐actuated reepithelization, dermal formation, and growth factors‐induced angiogenesis are crucial for wound healing. It is however, challenging to initiate both endogenous EF and growth factors in diabetic ulcer due to severe electrolyte loss and hyperglycemia‐resulted endothelial dysfunction. Current therapeutic systems supply electrostimulation by integrating self‐powered and conductive materials continue to encounter obstacles in nondegradability‐induced low biocompatibility and anisotropic EF‐resulted limited regeneration. Recombinant growth factors for angiogenesis are also limited in high cost, low stability, and potential bio‐risk. Herein, a wireless biocompatible thermoelectric hydrogel (HFN) co‐crosslinked by biodegradable hyaluronic acid and polyether F127 is developed to achieve effective directional‐EF stimulation. Target‐modified ginseng‐derived exosomes (RGE) is further embedded in the design of HFN‐RGE for enhanced diabetic ulcer healing. Specifically, HFN‐RGE recreates biomimetic EF through “cationic trap” effect to trigger robust epithelial and fibroblast electrotaxis, meanwhile controlling release of precise pro‐angiogenic exosomes with unique ability to reverse endothelial dysfunction. In vivo, HFN‐RGE is demonstrated to stimulate reepithelialization, dermal regeneration, and nascent vessel network reconstruction. Single‐cell RNA‐seq further revealed that HFN‐RGE activates the PPAR signaling‐meditated diabetic ulcer tissue regeneration. As such this work provides a promising electrical‐biological hybrid system with high biosafety for diabetic ulcer therapy.