PH‐Responsive Cu‐Fe‐MOF@Ag Nanocomposite Modulates Antibacterial and Anti‐Inflammatory Activity in Infected Wounds

ABSTRACT Bacterial colonization disrupts wound microenvironments, triggering oxidative stress and macrophage dysfunction that impede healing. Addressing the need for adaptive therapies, we developed a pH‐responsive metal‐organic framework (MOF) decorated with Ag nanoparticles (Cu‐Fe‐MOF@Ag) integrating 2‐methylimidazole, Cu 2 + , and Ag nanoparticles. Here, we synthesized this multifunctional material that autonomously modulates antibacterial and anti‐inflammatory activities in response to wound pH changes. Under acidic conditions, Cu‐Fe‐MOF@Ag achieved a 99.99% antibacterial rate against drug‐resistant Escherichia coli ( D–E. coli) at a concentration of 35 µg mL − 1 , and accelerated wound closure to 98% within 12 d. Its antibacterial mechanism arises from the synergistic effect of surface positive charge, reactive oxygen species (ROS), and released metal ions. As the pH shifts to alkaline, it scavenges excess reactive oxygen species, promoting macrophage polarization and tissue regeneration. In vivo, Cu‐Fe‐MOF@Ag accelerated the infected wound's closure, reduced inflammation, and enhanced collagen deposition and angiogenesis without systemic toxicity. This study presents a dynamic, infection‐responsive platform that synchronizes antibacterial and anti‐inflammatory regulation, offering a promising strategy for managing chronic and infected wounds.