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 mm 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.
Kofidis
T
T
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany. tkofidis@stanford.edu
Lenz
A
A
Boublik
J
J
Akhyari
P
P
Wachsmann
B
B
Mueller-Stahl
K
K
Hofmann
M
M
Haverich
A
A
D000818:Animals; D000831:Animals, Newborn; D019149:Bioreactors; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D046508:Culture Techniques / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005947:Glucose / Q000378:metabolism*; D018056:Hemorheology / Q000295:instrumentation* / Q000379:methods; D008567:Membranes, Artificial; D044085:Microfluidics / Q000295:instrumentation / Q000379:methods; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000000981:diagnostic imaging / Q000502:physiology*; D011673:Pulsatile Flow / Q000502:physiology*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods
D008567:Membranes, Artificial; D005947:Glucose