Light responsive chitosan hydrogel incorporated with PCN-224@berberine for antibiotic resistant bacterial infected wound management

Infections caused by multidrug-resistant bacteria significantly hinder wound healing, highlighting the need for non-antibiotic alternatives. Here, we developed a multifunctional hydrogel platform, LAMC@PCN-224@BBR, by incorporating photodynamic PCN-224 and the natural product berberine (BBR) into lipoic acid-modified chitosan (LAMC). This design combines photo-crosslinking for enhanced tissue adhesion with photodynamic therapy (PDT) for antimicrobial activity. Upon light irradiation, the hydrogel generates reactive oxygen species (ROS), effectively eradicating methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli ( E. coli ) with an efficiency exceeding 99 %. Its excellent biocompatibility and adaptive adhesion allow conformal coverage of irregular wounds. In a full-thickness skin defect model, the hydrogel accelerated healing by suppressing inflammation, promoting collagen deposition, enhancing angiogenesis, and polarizing macrophages toward the pro-regenerative M2 phenotype. These findings demonstrate that the LAMC@PCN-224@BBR hydrogel is a promising clinical strategy for controlling resistant infections and promoting tissue regeneration.