pH‐Adaptive Microneedle Patch Based on Cerium‐Based Prussian Blue Analogues for the Treatment of MRSA‐Associated Wound Infections

ABSTRACT The presence of biofilm formation, excessive inflammatory responses, and a dynamic microenvironment makes methicillin‐resistant Staphylococcus aureus (MRSA)‐associated chronic wound infections difficult to cure. To address this challenge, we developed a smart pH‐responsive hyaluronic acid microneedle patch (CV MN) loaded with vancomycin and cerium‐based Prussian blue analogs (CPB) for time‐coordinated therapy of MRSA‐infected wounds. This system realizes its function by using the dynamic pH changes during wound healing: in the acidic infectious microenvironment, vancomycin is rapidly released to exert powerful bactericidal effects, and the release of cerium ions from CPB is accelerated to scavenge reactive oxygen species (ROS) via its catalase (CAT) and superoxide dismutase (SOD) activities. When the pH becomes neutral during the repair phase, the continuously released cerium ions sustainably modulate the immune microenvironment. In vitro experiments demonstrated that CV MN exhibited excellent antibacterial activity and biofilm disruption efficacy against MRSA. CPB had potent ROS‐scavenging capacity, protected mitochondrial function, and promoted fibroblast migration, angiogenesis, and macrophage polarization toward the pro‐healing M2 macrophage phenotype. In mouse full‐thickness infected wound/abscess models, CV MN accelerated wound healing, reduced bacterial burden, attenuated inflammation, and reshaped immunity via an anti‐inflammatory program, providing a novel synergistic strategy for chronic infected wounds.