Elastin-like recombinamers-based hydrogel modulates post-ischemic remodeling in a non-transmural myocardial infarction in sheep

Ischemic heart disease is a leading cause of mortality due to irreversible damage to cardiac muscle. Inspired by the post-ischemic microenvironment, we devised an extracellular matrix (ECM)-mimicking hydrogel using catalyst-free click chemistry covalent bonding between two elastin-like recombinamers (ELRs). The resulting customized hydrogel included functional domains for cell adhesion and protease cleavage sites, sensitive to cleavage by matrix metalloproteases overexpressed after myocardial infarction (MI). The scaffold permitted stromal cell invasion and endothelial cell sprouting in vitro. The incidence of non-transmural infarcts has increased clinically over the past decade, and there is currently no treatment preventing further functional deterioration in the infarcted areas. Here, we have developed a clinically relevant ovine model of non-transmural infarcts induced by multiple suture ligations. Intramyocardial injections of the degradable ELRs-hydrogel led to complete functiona...