Dually Crosslinked Copper‐Poly(tannic acid) Nanoparticles with Microenvironment‐Responsiveness for Infected Wound Treatment

Abstract Reducing the burden of death due to wound infection is an urgent global public health priority. Metal‐phenolic networks (MPNs) have received widespread attention in antimicrobial infections due to their facile synthesis process, excellent biocompatibility, and antimicrobial properties brought about by polyphenols and metal ions. However, typical therapeutic MPNs show rapid release of metal ions due to their poor solution stability, impeding long‐acting efficacy in multiple wound healing stages. To address these issues, copper‐poly (tannic acid) nanoparticles (Cu‐PTA NPs): robust (dually crosslinked), microenvironment‐responsive, antibacterial, antioxidative, and anti‐inflammatory are prepared, which hierarchically modulate the infected wound healing process. Covalently polymerized via phenol‐formaldehyde condensation and crosslinked with bioactive Cu 2+ , reactive polyphenols are preserved, and Cu 2+ is efficiently entrapped in the PTA scaffold. The proposed strategy relieves the systemic toxicity, and only high reactive oxygen species (ROS)level as stimuli can “turn on” the catalytic activity of Cu 2+ to implement antibacterial therapy specifically in an infected wound. Systematic tissue regeneration assessment on the infected full‐thickness skin wounds of rats demonstrates enhanced wound healing rate. Cu‐PTA NPs enables the direct application in infected wound and exertion of long‐acting healing efficacy. This synergetic therapy strategy will pave the way for more complicated infections and inflammatory diseases.