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 in vivo and in vitro 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 in vitro 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.