Abstract
The epicardial surface of the heart is readily accessible during cardiac surgery and presents an opportunity for therapeutic intervention for cardiac repair and regeneration. As an important anatomic niche for endogenous mechanisms of repair, targeting the epicardium using decellularized extracellular matrix (ECM) bioscaffold therapy may provide the necessary environmental cues to promote functional recovery. Following ischemic injury to the heart caused by myocardial infarction (MI), epicardium derived progenitor cells (EPDCs) become activated and migrate to the site of injury. EPDC differentiation has been shown to contribute to endothelial cell, cardiac fibroblast, cardiomyocyte, and vascular smooth muscle cell populations. Post-MI, it is largely the activation of cardiac fibroblasts and the resultant dysregulation of ECM turnover which leads to maladaptive structural cardiac remodeling and loss of cardiac function. Decellularized ECM bioscaffolds not only provide structural support, but have also been shown to act as a bioactive reservoir for growth factors, cytokines, and matricellular proteins capable of attenuating maladaptive cardiac remodeling. Targeting the epicardium post-MI using decellularized ECM bioscaffold therapy may provide the necessary bioinductive cues to promote differentiation toward a pro-regenerative phenotype and attenuate cardiac fibroblast activation. There is an opportunity to leverage the clinical benefits of this innovative technology with an aim to improve the prognosis of patients suffering from progressive heart failure. An enhanced understanding of the utility of decellularized ECM bioscaffolds in epicardial repair will facilitate their growth and transition into clinical practice. This review will provide a summary of decellularized ECM bioscaffolds being developed for epicardial infarct repair in coronary artery bypass graft (CABG) surgery.
Highlights
TO HEART FAILUREHeart failure is a chronic and progressive condition characterized by maladaptive structural cardiac remodeling and poor cardiac pump function
We have shown that the interaction of human cardiac fibroblasts with CorMatrix R Extracellular matrix (ECM) results in a robust fibroblast growth factor-2 (FGF-2) dependent cell-mediated paracrine response capable of stimulating new blood vessel assembly [65]
A unique opportunity exists to augment surgical revascularization via coronary artery bypass graft (CABG) surgery using acellular ECM bioscaffold therapy
Summary
Heart failure is a chronic and progressive condition characterized by maladaptive structural cardiac remodeling and poor cardiac pump function. There are an increasing number of individuals living with heart failure, with 960,000 new cases reported each year in the US alone [2]. Biomaterials for the Surgical Management of Heart Failure will be living with heart failure in the US by 2030 [3]. Heart failure is often referred to as a “revolving door condition” due to high rates of readmission. Given its increasing prevalence and high rate of readmission, it is necessary to improve our understanding of the surgical management of heart failure. Extracellular matrix (ECM) bioscaffolds may be the key to unlocking the potential of the epicardial surface of the heart with the ultimate goal of driving endogenous mechanisms of repair and attenuating progressive heart failure following ischemic injury
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