Electroactive microneedle augmented stem cell therapy in myocardial infarction

Ischemic heart disease and related sequelae pose tremendous burdens on worldwide medical care. The excessive activation of cardiomyocytes and cardiac fibroblasts further exacerbates the prognosis after necrosis. Decades of stem cell therapy in preclinical studies suggested promising results in cardiomyocyte regeneration and tissue remodeling. However, few formulations achieved clinical translation due to the limited stem cell engraftment and insufficient arousal of resident cardiomyocytes. Here, we reported an implantable electroactive device to leverage stem cell therapy and cardiomyocyte restoration for effective heart recovery. Assisted by the piezoelectric microneedle patch with 80-cubic millimeter cavity, 1.5 × 10⁵ mesenchymal stem cells could be delivered efficiently to the infarcted site and sustained longer for continuous paracrine effects. Meanwhile, the piezoelectric stimulation generated from the poly(l-lactic) acid microneedle matrix further potentiated the stem cells and elicited more vigorous self-repair responses in cardiomyocytes. This approach was validated to effectively suppress inflammatory monocytes, reduce cardiomyocyte necrosis, and improve heart remodeling in a rat heart infarction model.