Whole Cardiac Tissue Bioscaffolds

Abstract

Bioscaffolds serve as structures for cells in building complex tissues and full organs including heart. Decellularizing cardiac tissue results in cell-free extracellular matrix (ECM) that can be used as a cardiac tissue bioscaffold. The field of whole-heart tissue engineering has been revolutionized since the 2008 publication of the first perfusion-decellularized whole heart, and since then, studies have shown how decellularized cardiac tissue retains its native architecture and biochemistry following recellularization. Chemical, enzymatic, and physical decellularization methods preserve the ECM to varying degrees with the widely accepted standard of less than 50 ng/mg of double-stranded DNA present in decellularized ECM. Following decellularization, replacement of cells occurs via recellularization: seeding cells into the decellularized ECM structure either via perfusion of cells into the vascular conduits, injection into parenchyma, or a combination of perfusion and injection. Endothelial cells are often perfused through existing vessel conduits to provide an endothelial lining of the vasculature, with cardiomyocytes and other parenchymal cells injected into the myocardium of decellularized ECM bioscaffolds. Uniform cell density and cell retention throughout the bioscaffold still needs to be addressed in larger animal models of the whole heart. Generating the necessary cell numbers and types remains a challenge. Still, recellularized cardiac tissue bioscaffolds offer therapeutic solutions to heart failure, heart valve replacement, and acute myocardial infarction. New technologies allow for decellularized ECM to be bioprinted into cardiac bioscaffolds or formed into a cardiac hydrogel patch. This chapter reviews the advances made in decellularization and recellularization of cardiac ECM bioscaffolds with a discussion of the potential clinical applications of ECM bioscaffolds.

Keywords: Cardiac extracellular matrix; Cardiac patches; Decellularization; Heart valves; Hydrogels; Recellularization.