Self-Powered Thermoelectric Hydrogels Accelerate Wound Healing

Electrical stimulation (ES) serves as a biological cue that regulates critical cellular processes, including proliferation and migration, offering an effective approach to accelerating wound healing. Thermoelectrics, capable of generating electricity by exploiting the temperature difference between skin and the surrounding environment without external energy input, present a promising avenue for ES-based therapies. Herein, we developed Ag₂Se@gelatin methacrylate (Ag₂Se@GelMA) thermoelectric hydrogels with high room-temperature thermoelectric performance and employed them as self-powered ES devices for wound repair. Systematic <i>in vivo</i> and <i>in vitro</i> investigations elucidated their biological mechanisms for enhancing wound healing. Our findings reveal that the Ag₂Se@GelMA thermoelectric hydrogels can significantly accelerate the wound closure by amplifying the endogenous electric field, thereby promoting cell proliferation, migration, and angiogenesis. Comprehensive <i>in vitro</i> experiments demonstrated that ES generated by the hydrogels activates voltage-gated calcium ion channels, elevating intracellular Ca²⁺ levels and enhancing mitochondrial functions through the Ca²⁺/CaMKKβ/AMPK/Nrf2 pathway. This cascade improves mitochondrial dynamics and angiogenesis, thereby accelerating tissue regeneration. The newly developed Ag₂Se@GelMA thermoelectric hydrogels represent a marked progress in wound dressing technology with the potential to improve clinical strategies in tissue engineering and regenerative medicine.