Bioartificial grafts for transmural myocardial restoration: a new cardiovascular tissue culture concept.
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.
Kofidis
Theo
T
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany. tkofidis@stanford.edu
Lenz
Andre
A
Boublik
Jan
J
Akhyari
Payam
P
Wachsmann
Bjoern
B
Stahl
Knut Mueller
KM
Haverich
Axel
A
Leyh
Rainer G
RG
D000818:Animals; D001011:Aorta / Q000502:physiology; D021522:Bioartificial Organs; D019149:Bioreactors; D002470:Cell Survival; D018920:Coculture Techniques; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000000981:diagnostic imaging / Q000378:metabolism; D011673:Pulsatile Flow; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods*; D014055:Tomography, Emission-Computed