An infection-adaptive, NIR-regulated self-healing hydrogel for antibiotic-free MRSA-infected wound repair

Bacterial infection, oxidative stress, and persistent inflammation impede wound repair, and antibiotic-dependent treatment may promote the emergence of bacterial resistance. We developed an infection-adaptive, near infrared (NIR) regulated self-healing hydrogel dressing (PACH) comprising polydopamine anchored silver nanostructures (PDA@Ag) within a dynamic Schiff base network of carboxymethyl chitosan and oxidized hyaluronic acid. Because Methicillin-resistant Staphylococcus aureus (MRSA) secretes hyaluronidase during infection, the oxidized hyaluronic acid network was designed to undergo infection-adaptive degradation; NIR-induced photothermal heating further loosened and disassembled the network, thereby increasing the accessibility of PDA@Ag-related antibacterial components. PDA@Ag exhibited enhanced NIR absorption and photothermal performance (ΔT _max  = 35.7 °C at 0.75 W/cm 2 ). PACH protected fibroblasts against H₂O₂ induced oxidative injury, promoted fibroblast migration, and attenuated inflammatory responses in lipopolysaccharide stimulated macrophages. In vitro, PACH exhibited potent antibacterial and antibiofilm activity against MRSA, with 808 nm irradiation reducing relative bacterial viability to 0.001%. In an MRSA infected full-thickness wound model, PACH with NIR reduced relative bacterial viability to 1.42 ± 0.59% on Day 3 and residual wound area to 2.518 ± 0.97% on Day 14, and enhanced re-epithelialization, collagen deposition, angiogenesis, and macrophage polarization toward a reparative phenotype without evident systemic toxicity. PACH is therefore a bio based hydrogel that forms in water at room temperature without organic solvents and provides antibacterial treatment without conventional antibiotics. These findings support an integrated dressing strategy for bacterial control and wound repair. Download: Download high-res image (148KB) Download: Download full-size image