Decellularization of whole hearts for cardiac regeneration

Cardiovascular disease is an important public health problem. Heart transplantation remains the definitive treatment for patients with end-stage heart failure (ESHF), but the availability of donor hearts falls short of the need. Although the use of mechanical devices has emerged as an alternative solution, these devices have several limitations. Tissue engineering techniques that utilize cells and regenerative medicine for the treatment of various heart diseases including ESHF have shown promise as new approaches in cardiovascular research. For the reconstruction of new tissues, scaffolds (i.e., biomaterials to be used as supports), cells, and appropriate growth factors are needed. Because the biomaterial plays an important role in the attachment of human cells and their functional integrity, generating an ideal scaffold is the greatest challenge in tissue engineering. A decellularized heart composed of native extracellular matrix has been shown to offer a complex, unique, and natural scaffold that provides both physical and chemical cues required for cardiac function. In this chapter, the key steps of reconstructing a whole heart from a decellularized scaffold are described, including procedures before decellularization (e.g., perfusion methods), during decellularization (e.g., monitoring of flow dynamics and outflow turbidity and viscosity), and after decellularization (e.g., disinfectant treatments, biomechanical and microstructural property evaluation). Remaining challenges in the field of cardiac regenerative research are also discussed.