Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue

Biotechnology and Bioengineering - Tập 93 Số 2 - Trang 332-343 - 2006
Milica Radisic1,2, Jos Malda3,4, Eric Epping5, Wenliang Geng1, Róbert Langer1,2, Gordana Vunjak‐Novakovic6,2,7,8
1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts
2Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts
3Institute for BioMedical Technology, University of Twente, Enschede, The Netherlands.
4Tissue BioRegeneration and Integration, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia
5Royal Netherlands Institute for Sea Research, Den Hoorn, The Netherlands
6Department of Biomedical Engineering, Columbia University, New York, New York
7fax: (212) 854-8725
8telephone: (212)-854-5459

Tóm tắt

AbstractFor clinical utility, cardiac grafts should be thick and compact, and contain physiologic density of metabolically active, differentiated cells. This involves the need to control the levels of nutrients, and most critically oxygen, throughout the construct volume. Most culture systems involve diffusional transport within the constructs, a situation associated with gradients of oxygen concentration, cell density, cell viability, and function. The goal of our study was to measure diffusional gradients of oxygen in statically cultured cardiac constructs, and to correlate oxygen gradients to the spatial distributions of cell number and cell viability. Using microelectrodes, we measured oxygen distribution in a disc‐shaped constructs (3.6 mm diameter, 1.8 mm thickness) based on neonatal rat cardiomyocytes cultured on collagen scaffolds for 16 days in static dishes. To rationalize experimental data, a mathematical model of oxygen distribution was derived as a function of cell density, viability, and spatial position within the construct. Oxygen concentration and cell viability decreased linearly and the live cell density decreased exponentially with the distance from the construct surface. Physiological density of live cells was present only within the first 128 µm of the construct thickness. Medium flow significantly increased oxygen concentration within the construct, correlating with the improved tissue properties observed for constructs cultured in convectively mixed bioreactors. © 2005 Wiley Periodicals, Inc.

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Biotechnology and Bioengineering

Tập 93 Số 2

332-343

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