Hyaluronic acid-based hybrid hydrogel synergizes antibacterial and anti-inflammatory activity for accelerated wound healing.

Chronic and infected wounds remain a major clinical challenge due to persistent bacterial infection and prolonged inflammation. Hyaluronic acid (HA), a natural polysaccharide with excellent biocompatibility and tissue regenerative properties, has shown great promise in wound management. To overcome the limitations of conventional wound dressings, we developed a multifunctional hyaluronic acid-based hydrogel (HMGF), co-functionalized with glycyrrhizic acid (GA) and Fe3+. The hydrogel was synthesized via ionic and photocrosslinking of methacrylated hyaluronic acid (HAMA) and acrylamide (AM), combining the structural and biological advantages of HA with the antibacterial and anti-inflammatory properties of GA and Fe3+. The resulting HMGF hydrogel exhibited rapid in situ gelation, tunable mechanical strength, and excellent cytocompatibility. In vitro and in vivo studies demonstrated its potent antibacterial activity, suppression of pro-inflammatory cytokines, and accelerated wound closure, reaching 90 % healing by day 14. Importantly, histological and systemic evaluations confirmed its biosafety. The photocrosslinked hydrogel enables spatiotemporal regulation of infection-inflammation microenvironments, offering a potent strategy for infected wound management.