Photo-Cross-Linkable Hydrogel with Lubricating, Antimicrobial, and Antioxidant Properties for Bacteria-Infected Wound Healing

Wound healing is a prolonged physiological process involving a series of complicated biological responses influenced by various factors, such as bacterial infection and oxidative damage. Existing treatments, while effective, have certain limitations in terms of biocompatibility, responsiveness to the wound environment, and efficacy in promoting tissue regeneration. To address these shortcomings, bioinspired by hydration lubrication mechanism of articular cartilage, we successfully designed and developed an injectable in situ photo-cross-linkable hydrogel, which was synthesized via modifying aminated hyaluronic acid with a polymer obtained by free radical polymerization of o-nitrobenzyl alcohol derivative (NB) and 2-methoxyethyl phosphocholine (MPC). The hydrophilic hydration layer formed around the zwitterionic charges in MPC endowed the hydrogel with enhanced lubrication and antimicrobial effects, whereas the hydroxymethyl group in NB enabled the hydrogel to process ultraviolet light-induced cross-linking property. The hydrogel, doped with polydopamine nanoparticles, facilitated multifaceted wound healing by the mechanism of photothermally responsive antibacterial, anti-inflammation, and angiogenesis. Specifically, upon injection of the hydrogel precursor solution into the wound site and exposure to ultraviolet light, the hydrogel cross-linked and adhered closely to the skin tissues, achieving hemostasis and exudate absorption. Additionally, the hydrogel showed excellent reactive oxygen species scavenging property, reducing cellular oxidative stress and meanwhile promoting the bactericidal effect with near-infrared light irradiation. Furthermore, the hydrogel, with its networked porous structure, was conducive to cell adhesion and proliferation, remarkably enhancing the cellular activity and tissue regeneration. The wound-healing performances of the hydrogel were investigated in both in vitro and in vivo experiments, showcasing its potential for wound treatment applications, offering a promising improvement over the current methods by providing a photothermal responsive, biocompatible, and effective healing process.