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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Brown, DA; MacLellan, WR; Laks, H; Dunn, JCY; Wu, BM; Beygui, RE

Published Date

  • July 1, 2007

Published In

Volume / Issue

  • 97 / 4

Start / End Page

  • 962 - 975

PubMed ID

  • 17195988

International Standard Serial Number (ISSN)

  • 0006-3592

Digital Object Identifier (DOI)

  • 10.1002/bit.21295


  • eng

Conference Location

  • United States