Near-infrared-triggered synergistic therapy with a Ru-based nanocomposite hydrogel for eradicating multidrug-resistant wound infections.

The increasing prevalence of antimicrobial-resistant pathogens necessitates the development of innovative treatment strategies. To address this challenge, we designed a multifunctional hydrogel (RBP) by embedding berberine-loaded, polyethylenimine-modified mesoporous ruthenium nanoparticles (BBR@Ru NPs-PEI) into a carboxymethyl chitosan network. The resulting RBP hydrogel exhibited excellent mechanical properties, a porous structure facilitating oxygen and moisture exchange, and remarkable photothermal conversion efficiency (49.03%). Under 808 nm NIR irradiation, the hydrogel generated rapid localized hyperthermia. In vitro studies demonstrated potent, broad-spectrum antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, achieving over 99.9% bacterial eradication. The bactericidal mechanism involved synergistic effects of NIR-induced hyperthermia causing membrane damage, intracellular content leakage, and reactive oxygen species (ROS) burst. Furthermore, the RBP hydrogel-NIR(+) treatment effectively disrupted pre-formed biofilms and downregulated key virulence genes. In a full-thickness MRSA-infected mouse wound model, the RBP hydrogel combined with NIR irradiation significantly accelerated wound closure, reduced bacterial load by 99.9%, and promoted a regenerative microenvironment by downregulating pro-inflammatory cytokines (IL-6, CRP) and upregulating vascular endothelial growth factor (VEGF). Comprehensive biosafety evaluations confirmed excellent biocompatibility, and hemocompatibility (hemolysis rate <3%), and no systemic toxicity. This work presents a safe and effective photothermal hydrogel platform that synergistically eliminates MRSA and promotes tissue regeneration, offering a promising therapeutic strategy for managing complex wound infections.