Fabrication of a 3-dimensional Cardiac Tissue using a Modular Tissue Engineering Approach

Implantation of engineered cardiac tissue may restore lost cardiac function to damaged myocardium. We propose that functional cardiac tissue can be fabricated using a modular, vascularized tissue engineering approach developed in our laboratory. In this study, rat aortic endothelial cells (RAEC) were coated onto sub-millimetre size modules embedded with cardiomyocyte-enriched neonatal rat heart cells (CM) and assembled into a contractile, macroporous sheet-like construct. Cell morphologies, contractility and responsiveness to electrical stimulus were examined to evaluate the function of the resulting modular construct. CM embedded modules contracted spontaneously at day 7 post-fabrication and remained viable in vitro at day 14. Modules cultured in 10% bovine serum were more contractile and responsive to external stimulus compared to 10% FBS medium cultured modules. VE-cadherin staining showed a confluent layer of RAEC on CM embedded co-culture modules at day 7. Co-culture modules were also contractilie, but when compared to CM only modules their electrical responsiveness was slightly diminished. Modules assembled into macroporous sheets retained their characteristics at day 10 postassembly. Micrographs from histological sections revealed the existence of muscle bundles near the perimeter of modules and at inter-module junctions.