A spatiotemporally coordinated curcumin-based microneedle patch for SDF-1α delivery and synergistic myocardial infarction therapy

INTRODUCTION: Effective myocardial regeneration following infarction remains a major clinical challenge due to the complex and dynamic pathological microenvironment. Current clinical management fails to adequately modulate the dynamic infarct microenvironment, where dysregulated inflammation and insufficient angiogenesis represent key therapeutic targets. METHODS: To address this challenge, we developed a spatiotemporally coordinated microneedle (MN) patch based on curcumin-conjugated gelatin methacrylate (Cur-GelMA) hydrogel for co-delivery of curcumin and stromal cell-derived factor-1α (SDF-1α). RESULTS: The engineered Cur-GelMA network significantly enhanced curcumin solubility and bioavailability, while PDMS micromolding enabled fabrication of mechanically robust MN patches. This integrated system provides rapid, reactive oxygen species-responsive curcumin release along with sustained SDF-1α delivery, achieving spatially targeted penetration and localized drug deposition in the infarcted myocardium. In vitro studies demonstrated that curcumin-hydrogel effectively reprogrammed macrophage polarization from pro-inflammatory M1 to reparative M2 phenotype, downregulating pro-inflammatory cytokines while upregulating anti-inflammatory cytokine. Simultaneously, sustained SDF-1α release promoted endothelial cell proliferation, migration, and tube formation via VEGF pathway activation. In a rat MI model, the SDF-1α@Cur-MN patch significantly improved recovery of cardiac function, attenuated fibrosis, enhanced M2 macrophage infiltration, and promoted mature neovessel formation. CONCLUSION: This dual-target MN system provides a coordinated approach to regulating inflammation and angiogenesis, demonstrating therapeutic potential for myocardial repair.