ABSTRACT
Ischemic heart disease kills millions of people across the world every year and has contributed to >13% of total global deaths in 2012 [1]. The vast majority of these heart diseases are slow, degenerative conditions that eventually lead to heart failure over a period of months to years. Thus, there is time and opportunity to intervene in the disease process and repair the damage. The heart, however, does not have the ability to regenerate or undergo repair that is sufficient to overcome myocardial infarction (MI) or other types of cardiomyopathy. A substantial number of therapies have been developed to mitigate the disease processes, but these efforts generally only slow disease progression. Over the past decade, advances in cardiac tissue engineering have demonstrated that it is possible to generate myocardium-like tissue constructs with structural and functional properties that start to recapitulate native muscle. However, the contractile properties and size have remained limited, demonstrating that significant improvements are still needed. For example, neonatal rat cardiomyocytes have been used to engineer cardiac muscle with electromechanical properties that are comparable to native tissue [2–6] and implanted back into rat heart to augment contractile function. Similar techniques have enabled the engineering of myocardium from embryonic stem cell (ESC)-derived cardiomyocytes as well [7–9]. However, these constructs are often of low density and not well aligned. Further, vascularization is only achieved when constructs are implanted in vivo and/or cocultured with endothelial cells in specific conditions. Thus, organizing cardiomyocytes, and potentially endothelial cells, to approximate or mimic the 3D structure of stereotypical myocardium is still a major and unresolved challenge.
