Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair

Highlights •Acellular ECM scaffolds retain bioactive properties capable of stimulating endogenous myocardial repair pathways that could be leveraged therapeutically to promote adaptive cardiac remodeling toward functional recovery after ischemic injury. •In rodents with MI, acellular bioactive ECM scaffolds surgically implanted on the epicardium stimulate adaptive cardiac repair and functional recovery with therapeutic effects highly dependent on the bioinductive properties of the biomaterial. •Interaction of human cardiac fibroblasts with bioactive ECM scaffolds can induce a robust FGF-dependent cell-mediated vasculogenic paracrine response capable of stimulating functional blood vessel assembly. •Acellular bioactive ECM scaffolds surgically implanted on the epicardium post-MI can reprogram resident fibroblasts and stimulate adaptive proreparative pathways enhancing functional recovery. •A novel surgical strategy for tissue repair is introduced that can be performed as an adjunct to conventional surgical revascularization with minimal translational challenges.