Injectable BMSC‐Based Extracellular Matrix‐Mimicking Microtissue for Myocardial Infarction Repair

After myocardial infarction, the myocardial microenvironment is altered by cardiomyocyte loss, inflammation, and extracellular matrix degradation, creating a hostile environment that severely limits bone marrow-derived mesenchymal stem cell (BMSC) survival, migration, and differentiation. The BMSCs may differentiate into cardiomyocyte-like cells in vitro. However, this potential remains significantly limited in vivo because of the lack of supportive signals and conducive microenvironments. To overcome these challenges, this study presents a novel injectable biomimetic microtissue system containing a dual biomimetic extracellular matrix scaffold consisting of Janus Basic Nanotubes, laminin, stromal-derived factor-1 alpha, and vascular endothelial growth factor (JLSV) for BMSC delivery (JLSV-BMSC microtissue) designed to mimic the natural myocardial microenvironment. In vitro experiments showed that the microtissue enhanced BMSC survival, proliferation, migration, anti-apoptotic capacity, and paracrine signaling under oxygen-glucose deprivation conditions. In vivo studies have shown that the microtissue significantly improves BMSC retention at the infarct site, directs their differentiation into cardiomyocytes and endothelial cells, reduces myocardial fibrosis and apoptosis, and promotes angiogenesis, contributing to improved cardiac remodeling and functional recovery. These results suggest that the JLSV-BMSC microtissue is a promising therapeutic strategy for myocardial infarction that addresses the critical challenges of stem cell-based therapies.