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

Zhiyue Feng,Shiqi Chen,Ke Han,Qiang Ma,Boyan Sun,Chujun Liu,Qiqi Wang,Hao Zhao,Zimo Liu,Junying He,Zhimeng Zhang,Haiyang Jiang

Published 2025 in International Journal of Biological Macromolecules

ABSTRACT

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.

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