Chitosan-based double-network hydrogel with synergistic photothermal/nitric oxide therapy for methicillin-resistance Staphylococcus aureus infected wound healing.

The development of advanced wound dressings that incorporate synergistic antibacterial strategies is essential for addressing antibiotic-resistant infections and facilitating tissue regeneration. This study presents a near-infrared (NIR)-responsive double-network hydrogel (Gel@HS) that combines photothermal therapy (PTT) and nitric oxide (NO) gas therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The hydrogel was engineered with acrylamide as the primary network and chitosan, a carbohydrate polymer, as the secondary network, capitalizing on chitosan's natural tissue adhesion and antibacterial properties. Hollow copper sulfide nanoparticles (HCuS) and sodium nitroprusside (SNP) were incorporated to enable photothermal conversion and controlled NO release upon NIR irradiation. The hydrogel demonstrated remarkable mechanical stability, adhesion, and targeted antibacterial activity, facilitating bacterial eradication through PTT-induced membrane disruption and NO-mediated protein inactivation. In vitro experiments confirmed its broad-spectrum antibacterial efficacy (>99 % MRSA elimination) and anti-inflammatory effects via macrophage modulation. In vivo testing using an MRSA-infected murine wound model showed accelerated healing (93 % wound closure within 9 days), reduced bacterial load, and diminished inflammatory cytokine levels. This research highlights the potential of carbohydrate polymer-based hydrogels as multifunctional platforms for combating resistant infections and promoting wound healing through physicochemical synergy.