Pulsatile perfusion and cardiomyocyte viability in a solid three-dimensional matrix

Background: The manufacture of full thickness three-dimensional myocardial grafts by means of tissue engineering is limited by the impeded cellular viability in unperfused in vitro systems. We introduce a novel concept of pulsatile tissue culture perfusion to promote ubiquitous cellular viability and metabolism. Methods: In a novel bioreactor we established pulsatile flow through the embedded three-dimensional tissue culture. Fibrin glue served as the ground matrix wherein neonatal rat cardiomyocytes were inoculated. Fluor- Deoxy-Glucose-Positron-Emission Tomography (FDG-PET) and life/dead assays were employed for comparative studies of glucose uptake resp. cell viability. Results: A solid 8 turn thick structure resulted. Cellular viability significantly increased in the perfused chambers. We observed centripetal migration of the embedded cardiomyocytes to the site of the core vessel. However, cellular viability was high in the periphery of the tissue block too. FDG-PET revealed enhanced metabolic activity in perfused chambers. Conclusions: The present concept is highly effective in enhancing cellular viability and metabolism in a three-dimensional tissue culture environment. It could be utilized for various co-culture systems and the generation of viable tissue grafts. (C) 2003 Elsevier Ltd. All rights reserved.