Environmentally Responsive Catalytic Microneedles Enable Cascade Fenton Reaction for Antibacterial Therapy and Accelerated Infected Wound Healing

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ABSTRACT The persistence of bacterial biofilms and resistance limits the efficacy of traditional therapies, slowing tissue regeneration. Here, we report an innovative pH‐responsive catalytic microneedle system (GZIF@Fe MN) designed to combat bacterial infections by disrupting bacterial redox homeostasis through a cascade Fenton reaction, generating highly reactive hydroxyl radicals (·OH). The system utilizes a Schiff base reaction between oxidized hyaluronic acid and carboxymethyl chitosan to construct a pH‐sensitive microneedle matrix capable of transdermal and delivery of embedded glucose oxidase (GOx) and Fe 3+ ‐modified metal‐organic framework ZIF‐8 (ZIF@Fe) for deep tissue release. The catalytic product of GOx, gluconic acid, creates an acidic microenvironment that facilitates the degradation of ZIF@Fe, leading to the rapid release of Fe 3+ . Simultaneously, GOx catalyzes glucose metabolism to generate H 2 O 2 , which drives continuous production of ·OH, enhancing the bactericidal effect. In vitro studies demonstrate that the cascade reaction achieves nearly 99% bactericidal efficacy against S. aureus and E. coli . In vivo experiments reveal that GZIF@Fe MN promotes macrophage polarization toward the anti‐inflammatory M2 phenotype, thereby reducing excessive inflammation and facilitating tissue regeneration, with wound closure exceeding 90%. Overall, the GZIF@Fe MN system provides an effective antibacterial wound therapy strategy and offers new insights into the development of next‐generation antibacterial biomaterials.

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