Click chemistry-driven adhesive hydrogel for efficient healing of infected wounds through multistage comprehensive management

Infected wound treatment remains a critical challenge in clinical medicine. Although existing treatments, like local debridement, antimicrobial agents, and growth factor therapies, have demonstrated certain therapeutic effects, they primarily target only specific stages of wound healing. Moreover, the escalating issue of antibiotic resistance limits their efficacy. To address these challenges, this study employs click chemistry to develop a multifunctional composite hydrogel, aiming to provide a comprehensive and effective treatment strategy. This hydrogel hybrid system comprises methacrylated hyaluronic acid, sulfhydryl kappa-carrageenan, and tannic acid (referred to as HKT). By utilizing a one-step click chemistry strategy (thiol-ene reaction), we innovatively integrated a dynamically cross-linked network. This strategy eliminates toxic by-products while enabling sustained polyphenol release, establishing a therapeutic platform that orchestrates multistage interventions during infected wound management. The resulting composite hydrogel manifests appropriate mechanical characteristics, favorable rheological properties and strong tissue adhesiveness. Additionally, this hydrogel exhibits excellent antioxidant and antibacterial properties, with a ROS scavenging rate reaching 69.62% and an antibacterial efficacy of up to 99%. Furthermore, it demonstrates outstanding biocompatibility and a balanced ability to modulate inflammation and promote angiogenesis. <i>In vivo</i> studies reveal a significant enhancement in wound healing efficiency, with an improvement of 48.4% compared to the control group. This study provides a theoretical and practical foundation for the multistage comprehensive management of infected wound healing.