An Environmentally Tolerant 5A Hydrogel with Photothermal Effect for Frostbite Treatment.

Rapid rewarming is the most conventional and primary treatment for frostbite, yet effective adjunctive strategies remain absent. Conventional wound dressings, such as therapeutic hydrogels, tend to freeze and lack the necessary rewarming ability, rendering them unsuitable for direct application. Herein, we engineered an environmentally tolerant photothermal hydrogel, named 5A-Gel, featuring anti-swelling, anti-pressure, antioxidant, anti-freezing, and anti-drying capacities, for the treatment of frostbite. 5A-Gel was formed via dynamic crosslinking between gelatin and tea polyphenols in a glycerol/water solvent system. The incorporation of glycerol endowed the hydrogel with superior anti-swelling, anti-freezing, and anti-drying performance (remaining flexible at -20 °C and 37 °C for at least 60 days), along with concentration-dependent antioxidant activity due to tea polyphenols. Furthermore, 5A-Gel exhibited excellent photothermal effects, maintaining stable temperature and softness under 808 nm laser irradiation with robust cyclic durability. In addition, 5A-Gel showed slow degradability, excellent hemocompatibility, and favorable in vivo biosafety. Functionally, in a mouse frostbite wound model, photothermal rewarming therapy using 5A-Gel markedly expedited frostbite healing, promoting re-epithelialization, enhancing collagen deposition, alleviating inflammatory response, and stimulating neovascularization. Therefore, the as-prepared 5A-Gel serves as a competent therapeutic platform for in situ frostbite treatment and offers innovative principles for the rational engineering of high-performance hydrogel systems targeting frostbite tissue injuries.