Quaternized Chitosan-based Photothermal Antibacterial Hydrogel with Pro-vascularization and On-demand Degradation Properties for Enhanced Infected Wound Healing

Compromised skin barrier fails to prevent pathogenic bacterial invasion, leading to wound infection and potentially severe tissue damage, for which conventional wound dressings provide inadequate therapeutic outcomes. Herein, we have developed a multifunctional injectable hydrogel (QCS-APA/P@D@C) based on quaternized chitosan (QCS) and aldehyde-modified aliphatic polycarbonate (APA), incorporating Prussian Blue (PB) @Polydopamine (PDA) @Cu (P@D@C) submicron particles (SPs). This novel hydrogel exhibits photothermal antibacterial properties, on-demand removal capability, and Cu-facilitated wound healing enhancement. The QCS-APA/P@D@C hydrogel, crosslinked via dynamic Schiff-base bonds, exhibits remarkable antibacterial efficacy (>99 %) against various bacteria, including multidrug-resistant (MDR) bacteria, through the synergistic effects of QCS, Cu, and 808 nm near-infrared (NIR) photothermal effect. The hydrogel demonstrates rapid degradation (~12 min) upon exposure to N-acetylcysteine (NAC), facilitating on-demand removal and minimizing secondary trauma during dressing changes. Furthermore, the sustained release of Cu within 1-10 μM significantly enhances the migration and tube formation of human umbilical vein endothelial cells (HUVECs). In a Staphylococcus aureus (S. aureus)-infected wound model of Sprague-Dawley (SD) rats, the QCS-APA/P@D@C hydrogel demonstrated effectively modulating wound inflammation, promoting collagen deposition and angiogenesis, and accelerating wound closure. These findings demonstrate that the QCS-APA/P@D@C hydrogel can effectively promote the healing of bacterially infected wounds.