Multifunctionalized Silver-Based Metal-Organic Framework Cooperated with Berberine Hydrochloride: Orchestrating Antibacterial Synergy and Antioxidant Shield for Enhanced Repair of Infected Wounds

The development of multifunctional wound dressings that concurrently eradicate bacterial infections and orchestrate tissue regeneration remains a critical challenge in clinical wound management. Herein, we report the fabrication of a BBH/Ag-MOF composite, synthesized by integrating berberine hydrochloride (BBH) into a silver-based metal-organic framework (Ag-MOF). This hybrid platform synergistically combines the potent antimicrobial efficacy of Ag + with the broad-spectrum bioactivity of BBH. In vitro investigations demonstrate that BBH/Ag-MOF exerts robust inhibitory effects against both Gram-positive ( Staphylococcus aureus ( S. aureus ) and Methicillin-resistant Staphylococcus aureus ( MRSA )) and Gram-negative ( Escherichia coli ( E. coli ) and Multidrug-resistant Escherichia coli ( MDR E. coli )) bacteria, significantly prolonging the bacterial lag phase, reducing proliferation rates, and achieving a superior bactericidal efficiency at remarkably low concentrations. Mechanistically, BBH/Ag-MOF facilitates bacterial targeting through electrostatic attraction, disrupts membrane integrity via Ag + release, and triggers intracellular respiratory chain inhibition through the delivered BBH molecules. Furthermore, the composite effectively scavenges reactive oxygen species (ROS) and suppresses biofilm maturation, thereby rebalancing the hostile wound microenvironment into a pro-healing state. In vivo assessments in an S. aureus -infected murine wound model reveal that BBH/Ag-MOF significantly accelerates wound closure, enhances organized collagen deposition, and stimulates angiogenesis. These therapeutic outcomes are accompanied by the downregulation of pro-inflammatory cytokines (TNF-α and IL-6), with no detectable cytotoxicity or systemic toxicity. Collectively, this study establishes BBH/Ag-MOF as a biocompatible, multifunctional therapeutic agent that synergistically bridges antibacterial, antioxidant, and regenerative functions, offering a highly effective strategy for the advanced management of infected chronic wounds.