Myocardial infarction patients are confronted with severe cardiac pathologies that eventually result in heart failure. The regenerative potential of the adult heart is very limited and insufficient to replace damaged muscle mass, and therefore, heart transplantation is still the standard therapy for end-stage heart failure patients. In recent years, advances in cell therapy and tissue engineering have emerged as the new hope for novel therapeutic approaches with the aim to trigger myocardial regeneration after injury with newly generated cardiac cells and tissue constructs. In combination with a biocompatible matrix, stem cell-derived cardiomyocytes (SC-CMs) represent ideal candidates for cardiac cell therapy, and current research focuses on the development of cardiac constructs for implantation and scaffold material optimization. However, before these cell constructs can be safely used for human therapy, the Basic properties of SC-CMs and their interactions with the immediate environment need to be carefully investigated. A great challenge in this field is to achieve the same high degree of structural and functional differentiation and maturation of the newly generated cardiac cells to match the characteristics of adult myocytes, and so far, this has not yet been realized.
Here, we propose an in-depth characterization of cell-material interactions of single SC-CMs on custom-built 3D scaffolds. Our major aim is to identify the trigger mechanisms that drive cardiomyocyte maturation towards an adult phenotype. Using highly sophisticated methods of direct laser writing, modern cell culture and cell physiological approaches, we will investigate the effect of different scaffold geometries and cell contact sites on the morphological maturation, subcellular myofilament arrangement and contractile properties of SC-CMs. The gain of knowledge from these experiments will significantly influence future improvements in the development of cardiac constructs for myocardial repair.