Spatiotemporally Orchestrated Cardiac Microneedle Patch Modulates Post-Infarction Immunity and Fibrosis

作者：Yanshan Chen, Li Zhang, Li Zhang, Yu Ding, Tao Zheng, Ximei Dai, Jie Sheng, Zhiyue Wang, Yunming Zhang, Ma La, Jing Pan, Guifen Yang, Sheng Wang, Longjiang Zhang, Longjiang Zhang · 发表于：ACS Nano · 年份：2026 · DOI：10.1021/acsnano.6c02542 · 研究领域：Cardiac Fibrosis and Remodeling、Tissue Engineering and Regenerative Medicine、Cardiac electrophysiology and arrhythmias

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Following MI, the initial inflammatory cascade may cause secondary myocardial injury, with excessive fibrosis subsequently leading to long-term functional impairment. To rationally address the dynamic post-MI pathology, we screened nine representative metal ions and identified magnesium (Mg 2+ ) as a potent protective ion against hypoxia-induced cardiomyocyte injury and inflammation. We then developed a spatiotemporally orchestrated, dissolvable microneedle patch (Mg-AAV-MN) for smart drug delivery to mitigate both early inflammation and late fibrosis. This system comprised two core functional modules aligned with the post-MI pathological phases: A fast-acting “Pioneer Module” comprising Mg 2+ -loaded lipid nanoparticles to modulate the early inflammatory microenvironment during the inflammatory phase, and a sustained “Sustainer Module” enabling adeno-associated virus-mediated interleukin-10 delivery to suppress aberrant fibroblast activation and limit pathological fibrosis during the remodeling phase. A “bead-like” structure was designed to ensure precise, sustained drug delivery to the beating heart. In vivo studies validated that Mg-AAV-MN significantly reduced infarct size, improved cardiac function, and mitigated adverse ventricular remodeling. This spatiotemporally orchestrated design addresses the limitation of a single therapeutic time window, achieving temporally phased and spati...