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Eur J Cardiothorac Surg 2003;24:906-911
© 2003 Elsevier Science NL

Bioartificial grafts for transmural myocardial restoration: a new cardiovascular tissue culture concept

^a Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany
^b ARTISS GmbH, Hannover, Germany
^c Leibniz Laboratories for Biotechnology and Artificial Organs, Hannover, Germany

Received 8 January 2003; received in revised form 10 June 2003; accepted 21 July 2003.

^* Corresponding author. Cardiothoracic Surgery/Falk Research Center, 2 fl, Stanford University Medical School, 300 Pasteur Dr., Stanford CA 94305, USA. Tel.: +1-650-725-3828; fax: +1-650-725-3846
e-mail: tkofidis{at}stanford.edu

Objective: Survival of bioartificial grafts that are destined to restore cardiac function stands and falls with their nutrient supply. Engineering of myocardial tissue is limited because of lack of vascularization. We introduce a new concept to obtain bioartificial myocardial grafts in which perfusion by a macroscopic core vessel is simulated. Methods: We have designed an experimental reactor with multiple chambers for the production of bioartificial tissue or tissue precursors. By introduction of in- and output lines of distinct diameter and insertion of a core vessel into each chamber, we established pulsatile, continuous flow through the embodied three-dimensional tissue culture. In the present study, collagen components served as the ground matrix wherein neonatal rat cardiomyocytes were inoculated. For the assessment of cellular viability and distribution in comparison to static, non-perfused culture, fluor-desoxy-glucose-positron-emission-tomography and life/dead assays were employed. Results: We obtained 3D constructs of 8-mm thickness, which display high viability and metabolism (6.0±1.3^e-03 in the perfused vs. 4.0±0.3^e-03 in the unperfused chambers). The core vessel has the size of a human coronary and remained patent during the entire culture process. We observed centripetal migration of the embedded cardiomyocytes to the site of the core vessel. Cardiomyocytes partially resumed a spindle like form without additional stretch. Conclusions: The present dynamic tissue culture concept is highly effective in manufacturing thick, viable grafts for cardiac muscle restoration, which could be surgically anastomosable. The bioreactor may accommodate multiple types of cells and tissues for innumerable in vitro and in vivo applications.

Key Words: Myocardial grafts • Tissue engineering • Cardiomyocytes