Scab-Inspired Thermoresponsive Hydrogel Dressing for Accelerated Healing of Infected Wounds

Infected wounds pose persistent clinical challenges due to microbial colonization, sustained inflammation, and impaired tissue regeneration. Drawing inspiration from the multifunctional role of natural scabs, we developed a thermoresponsive hydrogel dressing that integrates four synergistic functions to address these barriers. The hydrogel, synthesized by copolymerizing poly(<i>N</i>-isopropylacrylamide) (PNIPAM) with trihydroxymethyl acrylamide (THMA) and incorporating silver ions, exhibits strong tissue adhesion, temperature-triggered contraction, broad-spectrum antibacterial activity, and dual pro-regenerative effects. Abundant hydroxyl groups enable firm interfacial adhesion, while thermoresponsive shrinkage mechanically approximates wound edges. In vitro, the hydrogel demonstrated excellent cytocompatibility, minimal hemolysis, potent bactericidal activity, suppression of pro-inflammatory macrophage responses, and enhanced angiogenesis. In vivo, application to full-thickness infected murine wounds markedly reduced bacterial burden and inflammation, promoted collagen deposition and neovascularization, and accelerated closure to nearly complete healing within 14 days, accompanied by YAP-mediated mechanotransduction. This scab-inspired strategy transforms hydrogel dressings from passive coverings into active therapeutic platforms by coengineering mechanical and biochemical cues, thereby addressing the dual challenges of infection control and impaired healing. Owing to its facile fabrication, durable adhesion, thermoresponsive contraction, and multifunctionality, this hydrogel holds strong potential for clinical translation in the treatment of complex acute and chronic wounds.