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Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue.

Publication ,  Journal Article
Brown, DA; MacLellan, WR; Laks, H; Dunn, JCY; Wu, BM; Beygui, RE
Published in: Biotechnol Bioeng
July 1, 2007

Cardiac tissue engineering has made notable progress in recent years with the advent of an experimental model based on neonatal cardiomyocytes entrapped in collage gels and purified basement membrane extract, known as "engineered heart tissues" (EHTs). EHTs are a formidable display of tissue-level contractile function and cellular-level differentiation, although they suffer greatly from mass transport limitations due to the high density of metabolically active cells and the diffusion-limited nature of the hydrogel. In this report, a mathematical model was developed to predict oxygen levels inside a one-dimensional, diffusion-limited model of EHT. These predictions were then compared to values measured in corresponding experiments with a hypoxia-sensitive stain (pimonidazole). EHTs were cast between two plastic discs, which allowed for mass transfer with the culture medium to occur in only the radial direction. EHTs were cultured for up to 36 h in the presence of pimonidazole, after which time they were snap-frozen, histologically sectioned, and stained for bound pimonidazole. Quantitative image analysis was performed to measure the distance from the culture medium at which hypoxia first occurs under various conditions. As tested by variation of simple design parameters, the trends in oxygen profiles predicted by the model are in reasonable agreement with those obtained experimentally, although a number of ambiguities related to the specific model parameters led to a general overprediction of oxygen concentrations. Based on the sensitivity analysis in the present study, it is concluded that diffusion-reaction models may offer relatively precise predictions of oxygen concentrations in diffusion-limited tissue constructs.

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Published In

Biotechnol Bioeng

DOI

ISSN

0006-3592

Publication Date

July 1, 2007

Volume

97

Issue

4

Start / End Page

962 / 975

Location

United States

Related Subject Headings

  • Tissue Engineering
  • Oxygen Consumption
  • Oxygen
  • Nitroimidazoles
  • Myocytes, Cardiac
  • Myocardium
  • Models, Cardiovascular
  • Indoles
  • Hydrogels
  • Fluorescent Dyes
 

Citation

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Brown, D. A., MacLellan, W. R., Laks, H., Dunn, J. C. Y., Wu, B. M., & Beygui, R. E. (2007). Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue. Biotechnol Bioeng, 97(4), 962–975. https://doi.org/10.1002/bit.21295
Brown, David A., W Robb MacLellan, Hillel Laks, James C. Y. Dunn, Benjamin M. Wu, and Ramin E. Beygui. “Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue.Biotechnol Bioeng 97, no. 4 (July 1, 2007): 962–75. https://doi.org/10.1002/bit.21295.
Brown DA, MacLellan WR, Laks H, Dunn JCY, Wu BM, Beygui RE. Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue. Biotechnol Bioeng. 2007 Jul 1;97(4):962–75.
Brown, David A., et al. “Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue.Biotechnol Bioeng, vol. 97, no. 4, July 2007, pp. 962–75. Pubmed, doi:10.1002/bit.21295.
Brown DA, MacLellan WR, Laks H, Dunn JCY, Wu BM, Beygui RE. Analysis of oxygen transport in a diffusion-limited model of engineered heart tissue. Biotechnol Bioeng. 2007 Jul 1;97(4):962–975.
Journal cover image

Published In

Biotechnol Bioeng

DOI

ISSN

0006-3592

Publication Date

July 1, 2007

Volume

97

Issue

4

Start / End Page

962 / 975

Location

United States

Related Subject Headings

  • Tissue Engineering
  • Oxygen Consumption
  • Oxygen
  • Nitroimidazoles
  • Myocytes, Cardiac
  • Myocardium
  • Models, Cardiovascular
  • Indoles
  • Hydrogels
  • Fluorescent Dyes