A Dual-Crosslinked Collagen/Hyaluronic Acid/Chitosan Hydrogel for Integrated Hemostasis and Infected Wound Healing

Abstract

Conventional wound dressings often fail to integrate rapid hemostasis, antibacterial protection, and a pro-regenerative microenvironment, leading to persistent infection and delayed healing in complex wounds. Herein, we report a multifunctional self-adhesive hydrogel for integrated hemostatic, antibacterial, and regenerative wound management with a synergistic dual-crosslinked network. The hydrogel is composed of methylacrylamide-modified type I collagen (ColMA), o-nitrobenzene-modified hyaluronic acid (HANB), and methylacrylamide-modified chitosan (CSMA), and can rapidly form in situ under UV irradiation through free-radical polymerization of methacrylamide groups and Schiff base reactions between HANB and amino groups on ColMA/CSMA. Once applied to infected wounds, the hydrogel rapidly seals the wound bed and adheres tightly to the tissue, where HANB contributes hemostatic and adhesive properties, CSMA provides intrinsic antibacterial activity to inhibit bacterial colonization, and ColMA offers extracellular matrix-mimicking cues to support cell adhesion and tissue regeneration. Through this coordinated mechanism, the hydrogel not only controls bleeding and reduces infection risk at the early stage but also promotes the growth of granulation tissue, re-epithelialization, and matrix reconstruction during the subsequent repair phase. This platform integrates wound closure, antibacterial defense, and tissue regeneration into a single dressing system, acting as a promising strategy for the treatment of infected wounds.