Chapter 38 – Cardiac Tissue Engineering

In the developed world, cardiovascular disease is responsible for the loss of more human lives than all cancers combined. Due to the minimal intrinsic ability of the adult heart to regenerate itself following injury, myocardial infarction (MI) results in rapid death of hundreds of millions of cardiomyocytes (CMs), and vigorous inflammatory response. Over subsequent weeks to months, fibroblasts (FBs) and endothelial cells (ECs) form granulation tissue and a dense collagenous scar that reduces the contractile function of the heart and leads to a pathological remodeling and, in many cases, heart failure. Adult CMs are terminally differentiated, and thus it is not possible to expand them to sufficient numbers starting from small cardiac biopsies. Current clinical trials focus on cell replacement through application of bone marrow mesenchymal stem cells, peripheral blood mononuclear cells, or resident cardiac cells. Most of these cell types have no intrinsic ability to give rise to a large number of CMs; instead they improve function through paracrine effects. Additionally, cells can be applied alone or in combination with different types and forms of biomaterials (e.g., hydrogels, scaffolds). An appropriate combination of a biomaterial, cell type, delivery method and requirements for tissue culture prior to implantation will depend on the specific type of heart disease and patient population. Here we provide design criteria for the generation of functional cardiac patches, and discuss different biomaterials and cell types used during the tissue engineering process.