Near-infrared-triggered photothermal/photodynamic anti-biofilm hydrogels encapsulated with antimicrobial peptide-modified copper-doped carbon quantum dots for methicillin-resistant Staphylococcus aureus-infected wound healing

The healing of wounds infected with drug-resistant bacteria has become a serious issue for the medical system, while designing an all stage biofilm-resistant wound dressing which can ideally address this problem still remains a challenge. Herein, we designed a photothermal/photodynamic/inherent synergistic antibacterial hydrogel based on caffeic acid grafted ε-poly-L-lysine (CE)-modified Cu-doped carbon quantum dots (CQDs-CE) and chitosan-phenylboronic acid (CSP)/oxidized dextran (OD)-based dual-dynamic-bond cross-linked hydrogels (CSP/OD/CQDs-CE) for the healing of methicillin-resistant Staphylococcus aureus (MRSA) infected wounds. The dual dynamic network crosslinked by pH-sensitive boronate esters and Schiff base bonds offers the hydrogel excellent self-healing properties and on-demand painless removal capacity. Mechanistically, antibacterial activity relied on membrane disruption by CE, reactive oxygen species generation from Cu-CQDs, photothermal/photodynamic damage mediated by CQDs, and electrostatic interactions from positively charged chitosan. Notably, the hydrogel achieved biofilm clearance ratios of 91.1 % in vitro and 90.6 % in vivo, markedly higher than those of the 6S Ag group (54.8 % and 64.0 %, respectively). Besides, the hydrogel exhibited good biocompatibility, injectability, antioxidant properties, and hemostatic properties. In MRSA-infected full-thickness skin defect models, wounds treated with CSP/OD/CQDs-CE1 + NIR showed a final healing ratio of 99.7 %, significantly surpassing that of Tegaderm™ hydrocolloid dressing (83.0 %). While effectively inhibiting infection, reduce inflammation, accelerate angiogenesis, and promote collagen deposition, suggesting great potential for the treatment of wounds infected with drug-resistant bacteria.