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

Abstract

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(N-isopropylacrylamide)-derived ABA triblock copolymer (TNOTN) and an aldehyde β-cyclodextrin (ACD) for rapid healing of full-thickness 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.