Tissue engineering (TE) is an emergent interdisciplinary field that promises to increase our understanding of challenging issues in biomedical research that may facilitate tissue regeneration, or the replacement of dysfunctional organs and tissues. An approach of TE integrates cell sources, and materials into in vitro engineered substrates that may facilitate generation of tissue- like constructs, which may be used to understand pathological conditions, test pharmacological agents or elucidate pharmacokinetics, or as cell constructs for tissue replacement. Cardiac tissue, with its native in vivo complexity, represents a major challenge when trying to explain its physio- anatomical characteristics in vitro. Advances in cardiovascular tissue engineering may be improved by incorporation of materials that mimic the complex heart tissue environment, preferably those derived from primary cell sources. My findings indicate that integrating a multi- scale surface topography. along with extracellular matrix elements (ECM). facilitates the generation of confluent anisotropic cell mono-layers of fetal cardiomyocytes (FCM), neonatal cardiomyocytes NNCM, or derived from murine and human embryonic stem cells (CMdESC). In the case of primary cardiac cells, cardiac fibroblasts CF promote cell survival and phenotype. Also, my findings provide insight into the Cardiac fibroblast subpopulation including the importance of signaling derived elements to promote generation of in vitro cardiac micro environments. Importantly I developed a novel simplistic, cost-efficient, tunable, multi- scale fabrication approach to produce cell culture substrates with multi-scale feature topography for the alignment of cells that improve cell connectivity while enhancing and maintaining phenotypic characteristics.

This study suggests that for promoting and enhancing functionality and phenotypic characteristics of CM cultured in in vitro conditions, it is favorable to integrate multiple biomimetic cardiac microenvironmental factors into tissue culture systems.