Infusible Extracellular Matrix Biomaterial Enhances and Expedites Cell-Specific Pro-Repair Following Acute Myocardial Infarction

Myocardial infarctions (MI) affect 805,000 people per year in the United States. To mitigate the pathological effects of MI, we have developed and investigated pro-reparative decellularized extracellular matrix (ECM) biomaterials: an intravascularly infusible ECM (iECM). However, no one has ever utilized single cell and spatially resolved transcriptomics to further probe how systemically administered infusible ECM can elicit pro-repair in an MI model. Thus, we utilize spatial transcriptomics and single nucleus RNA sequencing (snRNAseq) to further measure pro-repair in various cell types, and thus validate these findings with spectral flow cytometry.With iECM, we found pro-reparative macrophage activation, fibroblast remodeling, increased vasculature development, and cardioprotection. Thus, we depict the pro-reparative nature of decellularized ECM biomaterials on cardiac cell types and elucidate previously undiscovered therapeutic pathways, further demonstrating infusible ECM's potential as an MI therapy. Overall design: Gene expression profiling of 10x Genomic Chromium single nucleus RNA-Seq or Visium spatial transcriptomics from the left ventricular myocardium short axis sections on injured Sprague Dawley female rats (225-250 g). Injuries include I/R (45 minutes of ischemia followed by reperfusion).