Highly biocompatible Ag nanocluster-reinforced wound dressing with long-term and synergistic bactericidal activity

Clinical application of antibiotic-free agents like silver nanoparticle-derived materials remains a critical challenge due to their limited long-term antibacterial activity and potential system toxicity. Herein, a highly biocompatible Ag nanocluster-reinforced hydrogel with enhanced synergistic antibacterial ability has been developed. Specifically, bioactive curcumin was incorporated into lysozyme-protected ultrasmall Ag nanoclusters (LC-AgNCs) and further integrated with sodium alginate (Sa) hydrogel (LC-AgNCs@Sa) through multiple interaction forces. Due to the synergistic antibacterial activity, LC-AgNCs could effectively kill both S. aureus and E. coli bacteria with a concentration down to 2.5 μg mL^-1. In-depth mechanism investigations revealed that the bactericidal effect of LC-AgNCs lies in their bacterial membrane destruction, reactive oxygen species (ROS) production, glutathione depletion and prooxidant-antioxidant system disruption ability. Curcumin can mediate the intracellular ROS balance to protect NIH 3T3 cells from oxidative stress and improve the biocompatibility of LC-AgNCs@Sa. LC-AgNCs@Sa with long-term antibacterial ability can effectively protect the wound from bacterial invasion in vivo, and significantly accelerate the wound healing process due to their distinctive functions of inhibiting inflammatory factor (TNF-α) production, promoting collagen deposit and facilitating re-epithelization. This study provides a new, versatile strategy for the design of high-performance antibacterial dressing for broad infectious disease therapy.