Synergistic antioxidant and antibacterial hydrogel for accelerated wound healing through ROS scavenging and pathogen elimination

Wound management remains a significant clinical challenge due to bacterial infection, oxidative stress, and inflammation. To address these issues, we developed a multifunctional hydrogel, NO-GM/Fle@FD, by combining gelatin methacryloyl (GelMA), Pluronic F127 diacrylate (F127DA), the nitric oxide (NO) donor S-nitrosoglutathione (GSNO), and the antibiotic fleroxacin (Fle). The hydrogel allows rapid photopolymerization under 405 nm light, forming a robust network with controlled NO release and localized antibiotic delivery. In infected murine wound model, NO-GM/Fle@FD accelerated wound closure through three mechanisms: (1) infection suppression via fleroxacin-mediated bactericidal activity, (2) ROS scavenging to reduce oxidative damage, and (3) inflammatory modulation through sustained NO release. Histological analysis revealed complete re-epithelialization by day 10, reduced inflammation, and enhanced collagen deposition in the NO-GM/Fle@FD group. Immunofluorescence showed decreased IL-1β (pro-inflammatory) and increased IL-10 (anti-inflammatory), confirming the hydrogel's ability to resolve inflammation and counteract oxidative stress. This study demonstrates that NO-GM/Fle@FD effectively targets the infection-oxidative stress-inflammation triad, providing a promising therapeutic solution for treating infectious wounds, diabetic ulcers, burns, and other chronic complex wounds.