Infusible Extracellular Matrix Biomaterial Enhances Cell-Specific Pro-Repair Responses Following Acute Myocardial Infarction.

To mitigate the pathological effects of myocardial infarction, we developed and investigated a pro-reparative decellularized extracellular matrix (ECM) biomaterial, an intravascularly infusible ECM (iECM). However, the cellular and molecular mechanisms by which iECM mediates repair are unknown because investigations have relied on bulk techniques. Here, we leverage single-nucleus RNA sequencing (snRNAseq) to measure pro-repair responses in various cell types across acute timepoints (1, 3, and 7 days post infusion). In iECM, we found pro-reparative macrophage activation, fibroblast remodeling, increased vascular development, lymphangiogenesis, cardioprotection, and neurogenesis. These findings are validated through spatial transcriptomics. Thus, we define the pro-reparative nature of the decellularized ECM biomaterial on cardiac cell types and elucidate previously undiscovered therapeutic pathways, further demonstrating the potential of iECM as an MI therapy, as well as display the wealth of data generated from next-generation sequencing.