NIR Light‐Driven Photocatalytic Antibacterial Hydrogels for Synergistic MRSA Biofilm Eradication and Wound Regeneration

ABSTRACT The treatment of drug‐resistant bacterial biofilm infections remains a significant challenge in clinical practice. To address this challenge, 3D oxygen vacancy (OV)‐rich iron‐doped Bi ₂ O ₂ S (Fe‐Bi ₂ O _2‐X S, Fe‐BOS) nanoflowers (NFs) are synthesized for the first time via an ion‐exchange method. The resulting material exhibits a small band gap, abundant OVs, and favorable charge‐transfer properties. It also shows robust photothermal performance and strong photocatalytic reactive oxygen species (ROS)‐generation ability. Fe‐BOS@C/H Gel is subsequently prepared by crosslinking hydrazide‐modified chondroitin sulfate, the Fe‐BOS NFs, and oxidized hyaluronic acid via a dynamic Schiff reaction. Fe‐BOS@C/H Gel not only shows good hemostasis and injectability, but also achieves 97% methicillin‐resistant Staphylococcus aureus (MRSA) biofilm elimination. Transcriptomic analyses reveal that Fe‐BOS@C/H Gel operates through multiple antibacterial mechanisms, including the destruction of bacterial membranes and the regulation of oxidative stress pathways and metabolic networks. In vitro cell experiments show that Fe‐BOS@C/H Gel promotes cell proliferation and migration. In a mouse model of MRSA biofilm‐infected wounds, Fe‐BOS@C/H Gel under NIR light eliminates MRSA biofilm through localized high temperature and ROS storms, and promotes collagen deposition and angiogenesis without NIR light. This study provides an innovative solution that utilizes the synergistic strategy of “light‐driven antibacterial performance and pro‐regeneration” to treat drug‐resistant bacterial‐infected wounds.