Local Release of Copper Manganese Oxide Using HA Microneedle for Improving the Efficacy of Drug-Resistant Wound Inflammation

The production of bacterial toxins and excessive accumulation of reactive oxygen species (ROS) can induce localized oxidative stress, triggering an exaggerated immune response that impedes wound healing and culminates in chronic wounds. To address this issue, a microneedle (MN) system loaded with copper-manganese oxide (CMO) is developed to modulate the hyperimmune response in wounds. CMO@MN exhibits excellent antimicrobial and anti-inflammatory properties by effectively killing bacteria, scavenging ROS, and modulating macrophage polarization through their multiple enzymatic activities and photothermal properties. RNA sequencing revealed that CMO@MN improved the therapeutic effect on the infected skin of mice by balancing the ratio of M1/M2 macrophages and promoting cell migration and angiogenesis through the regulation of relevant pathways. Overall, this CMO@MN patch skillfully balances the complex issues between the immune response and wound healing and has potential applications in the treatment of other serious bacterial infections.