A core-shell microneedle patch coordinates early anti-inflammatory modulation and sustained pro-angiogenic stimulation for cardiac repair after myocardial infarction.

Myocardial infarction (MI) involves a temporally evolving pathological cascade, in which acute NLRP3 inflammasome-mediated inflammation and insufficient reparative angiogenesis sequentially contribute to adverse ventricular remodeling. However, most current therapies lack the spatiotemporal control needed to match these evolving therapeutic demands. Here, we developed a core-shell microneedle (MN)-based epicardial patch for spatiotemporally programmed MI treatment through sequential delivery of the NLRP3 inhibitor MCC950 and basic fibroblast growth factor (bFGF). The rapidly hydrating methacrylated hyaluronic acid (HAMA) shell enabled early release of MCC950 to suppress acute inflammatory injury, whereas the chitosan-based core and backing layer provided sustained bFGF release to support later angiogenesis. The resulting HAMA/CS MN patch exhibited a well-defined core-shell architecture, suitable mechanical strength, excellent cytocompatibility, and differentiated release behavior. In vitro, MCC950-loaded MN patches effectively suppressed oxygen-glucose deprivation-induced activation of the NLRP3 inflammasome, lowered the expression levels of caspase-1, IL-1β, and IL-18, and attenuated cardiomyocyte apoptosis. Meanwhile, sustained bFGF release substantially improved endothelial cell proliferation, migration, and tube formation. In a rat MI model, epicardial implantation of the dual-loaded MN patch reduced inflammatory activation, enhanced angiogenesis, decreased fibrosis, and showed greater preservation of cardiac function relative to untreated MI or single-agent controls. These findings demonstrate that core-shell MN-mediated sequential local delivery can align therapeutic kinetics with post-MI pathophysiology. This study provides a localized and programmable platform for cardiac repair and potentially for other dynamic inflammatory-regenerative diseases.