On-Demand Dissociable Antibacterial Self-Healing Hydrogel with Rapid Arginine-Related Biosynthesis Capacity to Promote Full-Thickness Bacteria-Infected Wound Healing

Developing a self-healing hydrogel wound dressing with intrinsic antibacterial and on-demand dissociable properties is highly desired yet challenging in clinician applications to enhance angiogenesis and collagen growth for rapid wound healing. Herein, we present a thermoresponsive self-healing hydrogel dressing with intrinsic antimicrobial property based on a poly(Nisopropylacrylamide)-derived ABA triblock copolymer (TNOTN) and an aldehyde beta-cyclodextrin (ACD) for rapid healing of fullthickness infected wounds. The prepared TNOTN-ACD hydrogel exhibits excellent thermal responsiveness with a well-defined thermal-induced sol-gel transition, allowing in situ gelling and on-demand removal of wound dressing via temperature switch. Meanwhile, the dynamic Schiff base bonds formed between TNOTN and ACD endow the hydrogel with excellent self-healing properties, which can maintain structural integrity for constant and effective antibacterial performance. Meanwhile, TNOTN-ACD hydrogels have good antibacterial properties against both S. aureus and E. coli, as well as good biocompatibility and hemocompatibility. More importantly, in vivo spatial metabolomics revealed that the TNOTN-ACD hydrogel dressing could accelerate angiogenesis and collagen deposition via the arginine-related biosynthesis pathways, thereby effectively promoting wound closure in a full-thickness bacteria-infected skin defect.