Near-infrared light-driven photocatalytic reactive oxygen species-generating antibacterial and self-shrinking hybrid hydrogels for combating drug-resistant bacterial biofilm infection and accelerating wound healing

The development of wound dressings with tunable antibacterial activity and controllable self-shrinkage remains an intractable medical task for treating drug-resistant bacterial biofilm-infected wounds. Herein, we prepared a near-infrared-light (NIR)-controlled hydrogel (Co-BOS@C/F Gel) using an oxygen vacancy (OV)-rich cobalt (Co)-doped bismuth oxysulfide (Co-Bi₂O_2-XS, Co-BOS) photocatalyst as the guest molecule and a hydrazide-modified chondroitin sulfate/aldehyde-terminated Pluronic F127 hydrogel (C/F Gel) as the host carrier. First, the two-dimensional Co-BOS photocatalysts were synthesized <i>via</i> a one-step liquid-phase ion-exchange method. Co doping decreased the band gap, increased the number of OVs, and promoted charge transfer. Co-BOS also exhibited excellent photothermal performance (<i>η</i> = 34.09 %) and strong photocatalytic reactive oxygen species (ROS)-generating ability. The Co-BOS@C/F Gel formed via a dynamic Schiff reaction showed good temperature sensitivity, adhesion, hemostasis, and electrical conductivity and unique NIR-light-driven self-shrinkage. It exhibited broad-spectrum antibacterial activity against various bacteria and eliminated 95 % of the methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) biofilm using photothermal therapy/antibacterial photocatalytic therapy. Integrated transcriptomic analyses revealed that the Gel operates <i>via</i> multiple antibacterial mechanisms, including the regulation of oxidative stress pathways and metabolic networks. Furthermore, this Gel significantly promoted cell proliferation and migration. In a mouse model of MRSA biofilm-infected wounds, the Co-BOS@C/F Gel under NIR light adaptively covered irregular wounds, eliminated MRSA biofilms, and accelerated wound closure. Without NIR light, the gel effectively promoted collagen deposition and angiogenesis. This study provides an innovative "kill four birds with one stone" strategy to treat drug-resistant bacteria-infected wounds and promotes the application of hybrid hydrogels in the biomedical field.