Multifunctional microneedle patch loaded with microfluidic-synthesized hybrid gas-nanozyme for myocardial infarction treatment

Myocardial infarction (MI) remains a critical global health challenge. Excessive reactive oxygen species (ROS) and intense inflammation are two primary drivers of myocardial injury, leading to cardiac dysfunction and heart failure. Herein, a multifunctional microneedle (MN) patch based on gelatin methacryloyl (GelMA) is developed to deliver a hybrid gas-nanozyme with antioxidant and anti-inflammatory activities for MI treatment. The hybrid gas-nanozyme (ZnSBS), comprising zinc sulfide (ZnS) and superoxide dismutase (SOD), is fabricated via microfluidic synthesis. It exhibits pH-responsive hydrogen sulfide (H₂S) release in the acidic myocardial microenvironment, thereby synergizing with SOD to enhance ROS scavenging and mitigate oxidative damage in vitro. Furthermore, ZnSBS promotes macrophage polarization toward the M2 phenotype, suppressing inflammatory cytokine secretion. Upon implantation of the MN patch onto the infarcted myocardium in a rat MI model, the patch exhibits strong cardiac adhesion and prolonged ZnSBS retention in infarcted area. This localized delivery effectively inhibits fibrosis, reduces infarct size and improves cardiac function by attenuating ROS-induced injury and inflammation in vivo. This innovative MN patch, integrated with microfluidic-synthesized hybrid gas-nanozyme, offers a promising strategy for MI treatment by targeting oxidative stress and modulating inflammatory.