Multifunctional injectable photothermal hydrogel with RuCo3O4-Au nanoarchitectures for combating drug-resistant infection and enhancing diabetic wound healing.

Chronic wounds represent a major global health burden. They are closely associated with drug-resistant bacteria (DRB), largely due to biofilm formation that impedes antimicrobial penetration and delays tissue healing and regeneration. To address these limitations, we developed hetero/nanoarchitectures combining ruthenium cobalt (IV) oxide (Ru-Co3O4)-doped spiky gold nanostars (Ag@Au), known as RCA, with high photothermal conversion efficiency and strong reactive oxygen species (ROS) generation. These hetero/nanoarchitectures were incorporated into a near-infrared (NIR)-responsive photothermal hydrogel based on biocompatible carboxymethyl chitosan and plutonic (PC@RCA) matrix. The as-fabricated PC@RCA hydrogel demonstrated enhanced bacterial killing and over 90% biofilm-destroying activity against both methicillin-resistant S. aureus (MRSA) and E. coli strains. Additionally, the synergistic effect of photothermal-ROS antibacterial action was confirmed by significant downregulation of key biofilm- and bacterial-survival-related genes identified by genomic and transcriptomic analysis. Concurrently, the hydrogel enhanced M2 macrophage polarization and keratinization-related gene expression in keratinocyte cells, while in vivo NIR-activated PC@RCA hydrogels promoted angiogenesis and epidermal regeneration, leading to scar-free wound healing in a diabetic wound model. Collectively, the PC@RCA hydrogel developed in this study not only represents a powerful antimicrobial platform for the treatment of antibiotic-resistant bacterial infections but also grants potential for next-generation chronic wound treatment.