Cysteine-Derived Carbon Dots Hydrogels with Visible-Light-Driven Photocatalytic Therapy for Infected Wound Healing

The escalating crisis of multidrug resistance and biofilm recalcitrance poses severe challenges to conventional wound management. Photocatalytic antimicrobial therapy (PCAT) represents a promising nonantibiotic alternative that triggers the generation of reactive oxygen species (ROS) under illumination, thereby achieving broad-spectrum sterilization. Herein, we engineered a metal-free, visible-light-driven photocatalyst based on cysteine-derived carbon dots (Cys-CDs) via a facile microwave-assisted approach. Through precise N, S-heteroatom doping, the Cys-CDs possess tailored bandgaps of 2.78 eV, conferring them with superior visible-light harvesting capability. Upon visible-light exposure, the photocatalytic generation of ROS drives potent antibacterial efficacy, achieving >95% bacterial eradication against Staphylococcus aureus at 31.25 μg/mL and Escherichia coli at 62.5 μg/mL. Importantly, the unique ROS-mediated antibacterial mechanism of Cys-CDs induces nonspecific oxidative damage to bacterial components, thereby fundamentally circumventing the evolution of resistance. Subsequently, Cys-CDs were covalently integrated into an alginate hydrogel matrix to construct a sustained-release platform (CCDs/SA). The resultant hydrogel retains robust photocatalytic antibacterial activity, demonstrating excellent performance in inhibiting biofilm formation and eradicating mature biofilms. Notably, the CCDs/SA hydrogel exerts selective bactericidal activity through differential enzymatic modulation, effectively eliminating bacteria while simultaneously promoting mammalian cell proliferation and migration. In an infected full-thickness skin wound model, the hydrogel combined with visible-light irradiation achieved near-complete bacterial eradication (99.07%) by day 7 and accelerated wound closure to 97.35% within 14 days, significantly outperforming commercial antibacterial dressings. Collectively, this work establishes a nonantibiotic therapeutic strategy for engineering visible-light-driven platforms, holding great promise for the clinical management of infected wounds.