Annals of Biomedical Engineering

, Volume 35, Issue 11, pp 1885-1897

First online:

Analysis of pH Gradients Resulting from Mass Transport Limitations in Engineered Heart Tissue

  • David A. BrownAffiliated withDepartment of Bioengineering, University of California, Los Angeles Email author 
  • , William R. MacLellanAffiliated withDepartments of Medicine, Physiology, and The Cardiovascular Research Laboratories, David Geffen School of Medicine University of California, Los Angeles
  • , Benjamin M. WuAffiliated withDepartment of Bioengineering, University of California, Los AngelesDepartment of Materials Science, University of California, Los Angeles
  • , Ramin E. BeyguiAffiliated withDepartment of Surgery, University of California, Los Angeles

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Transport limitations of critical nutrients are a major obstacle in the construction of engineered heart tissues (EHTs), and the importance of oxygen in this regard is well-documented throughout the literature. An indirect effect of cellular hypoxia is the shunt to the less-efficient glycolytic metabolism, which is accompanied by a reduction in extracellular pH. Image analysis of phenol red coloration in an experimental model of EHTs demonstrated pH gradients towards the center of the construct, which were dependent on experimental variables. Based on these observations, a four-species, 2-D diffusion–reaction mathematical model was developed to predict pH in a radial-diffusion model. The mathematical model predicted lethal values of pH (<6.5) in EHTs comprised of a nominal cell density of 106 cells/cm3. pH predictions were moderately dependent on O2 concentration, and strongly dependent on cell density, CO2 concentration, and diffusion path length. It can be concluded from this study that hypoxia-induced acidosis is an important element in the mass transport problem, and future experiments measuring pH with more sensitive methods is expected to further elucidate the extent of this effect.

Key terms

Cardiac tissue engineering Diffusion Hypoxia Hydrogel