A New Form of Decellularized Extracellular Matrix Hydrogel for Treating Ischemic Tissue via Intravascular Infusion

Extracellular matrix (ECM) hydrogels have been widely used in preclinical studies as injectable materials for tissue engineering therapies. We have developed a new ECM therapy, the soluble fraction derived from decellularized, digested ECM, for intravascular infusion. This new form of ECM is capable of gelation in vivo and can be delivered acutely after an injury to promote cell survival and improve vascularization. In this study, we show proof-of-concept for the feasibility, safety, and efficacy of ECM infusions using small and large animal models of acute myocardial infarction (MI) and intracoronary infusion. Following infusion, the ECM material was retained in the heart, specifically in regions of ischemia, and colocalized with endothelial cells, coating the leaky microvasculature. Functional improvements, specifically reduced left ventricular volumes, were observed after ECM infusion post-MI. Genes associated with angiogenesis were upregulated, and genes associated with cell apoptosis/necrosis and fibrosis were downregulated. The ECM was also delivered using a clinically-relevant catheter in a large animal model of acute MI. This study shows proof-of-concept for a new intravascular delivery strategy for ECM biomaterial therapies with potential implications for a variety of pathologies with ischemic tissue or injured vasculature.