Several issues need to be improved to construct better tissue engineered cardiac replacements.
- Better cell sources. Currently, there is no optimal cell source that is easy to harvest, unlimited, proliferate in large numbers, autologous and has the ability to differentiate into mature, functional cardiomyocytes
- Better survival rates of cardiac myocytes in a three-dimensional environment. In particular, these constructs need to be thicker (about 1 cm) to resemble native cardiac tissue. However, current bioreactors cannot supply enough nutrients and oxygen for that much thickness. Further, after implantation, these constructs need to be able to survive the ischemic state until new vessels can grow into the constructs and maintain viability and function.
- Better mechanical properties (particularly contractile function)
More research is needed to address the above limitation issues. The future work will focus on:
- Stem cell technologies – More research to settle controversial data on stem cells and an efficient and reproducible method is needed to control and direct differentiation of stem cells to the desired cell type.
- Gene therapy – More research to determine if genetic manipulations of cardiac myocytes may improve their regenerative potential.
- Cell biology – More research to increase understanding of interactions between cells and extracellular matrix, to identify all factors including optimal concentrations and time windows in which specific factors have to be present during culture, and to understand the interactions of vascularization and the construct.
- Mechanical properties and current strategies for constructing these tissue engineered cardiac replacements – More research is needed to determine how to create a replacement with better mechanical properties, in terms of matrix material modifications or varying cell compositions of sheets.