Crosslinker-free PVA/CS-ag@PDA hydrogel with controlled silver ion release and NIR-enhanced antibacterial activity for MRSA-infected diabetic wound repair

A crosslinker-free PVA/CS hydrogel with polydopamine-engineered Ag nanoparticles was developed. • The hydrogel shows strong tissue adhesion, mechanical robustness, and self-healing for long-term wound application. • PDA enables sustained Ag⁺ release and stable NIR-responsive photothermal heating. • Ag@PDA0.5 balances antibacterial efficacy, photothermal activity, and cytocompatibility. • NIR-mediated photothermal treatment reduces inflammation and promotes vascularization in MRSA-infected diabetic wounds. Chronic diabetic wounds complicated by multidrug-resistant bacterial infections remain a persistent clinical challenge, requiring advanced wound dressings that integrate effective antibacterial protection with tissue regeneration. Herein, we developed a biocompatible and crosslinker-free hydrogel system composed of polyvinyl alcohol (PVA) and chitosan (CS), integrated with polydopamine-coated silver nanoparticles (Ag@PDA). The PDA coating, together with the hydrogel matrix, regulated Ag + release, thereby maintaining antibacterial activity while reducing silver-associated cytotoxicity. The resulting PVA/CS-Ag@PDA hydrogel exhibited favorable mechanical properties, tissue adhesion, cytocompatibility, antioxidant activity, and broad-spectrum antibacterial efficacy. In vitro and in vivo experiments collectively demonstrated the pro-regenerative and immunomodulatory effects of the hydrogel. In vitro, the hydrogel promoted endothelial cell migration and regulated macrophage inflammatory responses, as evidenced by reduced pro-inflammatory markers and enhanced repair-associated gene expression. In an MRSA-infected diabetic rat wound model, PVA/CS-Ag@PDA treatment suppressed bacterial growth, attenuated inflammatory infiltration, downregulated pro-inflammatory genes including Il6 and Tnf, and upregulated repair-associated genes including Il10 and Mrc1. Moreover, Ag@PDA endowed the hydrogel with concentration-dependent near-infrared (NIR)-triggered photothermal behavior. Among the tested formulations, PVA/CS-Ag@PDA0.5 generated a moderate and stable photothermal response and was selected for NIR-assisted antibacterial treatment. Under NIR irradiation, PVA/CS-Ag@PDA0.5 further enhanced bacterial eradication against MRSA and E. coli . NIR-assisted treatment also reduced CD45 + inflammatory cell infiltration and CD68 + macrophage accumulation, enhanced CD206-associated reparative signaling, and improved epidermal remodeling, collagen deposition. This work presents a rational strategy for engineering silver-based hydrogel dressings with controlled Ag + release, NIR-enhanced antibacterial activity, and improved regenerative efficacy for infected diabetic wound repair. Download: Download high-res image (327KB) Download: Download full-size image