Synergistic and Long-Lasting Wound Dressings Promote Multidrug-Resistant Staphylococcus Aureus-Infected Wound Healing

BACKGROUND: Multidrug-resistant staphylococcus aureus infected wounds can lead to nonhealing, systemic infections, and even death. Although advanced dressings are effective in protecting, disinfecting, and maintaining moist microenvironments, they often have limitations such as single functionality, inadequate drug release, poor biosafety, or high rates of drug resistance. METHODS: Here, a novel wound dressing comprising glycyrrhizic acid (GA) and tryptophan-sorbitol carbon quantum dots (WS-CQDs) was developed, which exhibit synergistic and long-lasting antibacterial and anti-inflammatory effects. We investigated the characterization, mechanical properties, synergistic antibacterial effects, sustained-release properties, and cytotoxicity of GA/WS-CQDs hydrogels in vitro. Additionally, we performed transcriptome sequence analysis to elucidate the antibacterial mechanism. Furthermore, we evaluated the biosafety, anti-inflammatory effects, and wound healing ability of GA/WS-CQDs dressings using an in vivo mouse model of methicillin-resistant staphylococcus aureus (MRSA)-infected wounds. RESULTS: The prepared GA/WS-CQDs hydrogels demonstrated superior anti-MRSA effects compared to common antibiotics in vitro. Furthermore, the sustained release of WS-CQDs from GA/WS-CQDs hydrogels lasted for up to 60 h, with a cumulative release of exceeding 90%. The sustained-released WS-CQDs exhibited excellent anti-MRSA effects, with low drug resistance attributed to DNA damage and inhibition of bacterial biofilm formation. Notably, in vivo experiments showed that GA/WS-CQDs dressings reduced the expression of inflammatory factors (TNF-α, IL-1β, and IL-6) and significantly promoted the healing of MRSA-infected wounds with almost no systemic toxicity. Importantly, the dressings did not require replacement during the treatment process. CONCLUSION: These findings emphasize the high suitability of GA/WS-CQDs dressings for MRSA-infected wound healing and their potential for clinical translation.