Berberine@AgNPs@Carboxylated chitosan hydrogel dressing with immunomodulatory and anti-biofilm properties promotes wound repair in drug-resistant bacterial infections

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial strain resistant to multiple antibiotics frequently encountered in clinical settings. Excessive antibiotic use has increased bacterial resistance, leaving a lack of effective treatments for MRSA infections. MRSA often colonizes the surface of skin wounds, resulting in chronic inflammation and protracted wound healing. The biofilm formation hinders the complete eradication of the bacteria, exacerbating the local inflammatory response and impeding wound healing. This study presents an innovative methodology for managing MRSA-infected skin wounds. The novel immunomodulatory hydrogel composed of Berberine, silver nanoparticles (AgNPs), and carboxylated chitosan (designated as Ber@AgNPs@CHI hydrogel) demonstrates enhanced therapeutic efficacy in a murine model of MRSA skin infection. This hydrogel is effective in eradicating MRSA and preventing biofilm formation. Furthermore, it modulates the local immune microenvironment by facilitating the transition of macrophages from the M1 to M2 phenotype and increasing the production of vascular endothelial growth factor (VEGF). These actions collectively facilitate the progression of the wound from the inflammatory to the proliferative phase, enhancing the early stages of wound healing. Hence, this safe and effective hydrogel mediates wound healing from multiple perspectives and targets, providing a new potential avenue for treating persistent infected wounds caused by clinical MRSA.