The influence of bioreactor geometry and the mechanical environment on engineered tissues

A three phase model for the growth of a tissue construct within a perfusion bioreactor is examined. The cell population (and attendant extracellular matrix), culture medium and porous scaffold are treated as distinct phases. The bioreactor system is represented by a two-dimensional channel containin...

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Main Authors: Osborne, J.M., O'Dea, Reuben D., Whiteley, J.P., Byrne, H.M., Waters, S.L.
Format: Article
Published: American Society of Mechanical Engineers 2010
Online Access:https://eprints.nottingham.ac.uk/29049/
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author Osborne, J.M.
O'Dea, Reuben D.
Whiteley, J.P.
Byrne, H.M.
Waters, S.L.
author_facet Osborne, J.M.
O'Dea, Reuben D.
Whiteley, J.P.
Byrne, H.M.
Waters, S.L.
author_sort Osborne, J.M.
building Nottingham Research Data Repository
collection Online Access
description A three phase model for the growth of a tissue construct within a perfusion bioreactor is examined. The cell population (and attendant extracellular matrix), culture medium and porous scaffold are treated as distinct phases. The bioreactor system is represented by a two-dimensional channel containing a cell-seeded rigid porous scaffold (tissue construct) which is perfused with culture medium. Through the prescription of appropriate functional forms for cell proliferation and extracellular matrix deposition rates, the model is used to compare the influence of cell density-, pressure- and culture medium shear stress-regulated growth on the composition of the engineered tissue. The governing equations are derived in O'Dea \emph{et al.} (A multiphase model for tissue construct growth in a perfusion bioreactor, \emph{Math. Med. Biol.}, In press), in which the long-wavelength limit was exploited to aid analysis; here, finite element methods are used to construct two-dimensional solutions to the governing equations and to investigate thoroughly their behaviour. Comparison of the total tissue yield and averaged pressures, velocities and shear stress demonstrates that quantitative agreement between the two-dimensional and long-wavelength approximation solutions is obtained for channel aspect ratios of order $10^{-2}$ and that much of the qualitative behaviour of the model is captured in the long-wavelength limit, even for relatively large channel aspect ratios. However, we demonstrate that in order to capture accurately the effect of mechanotransduction mechanisms on tissue construct growth, spatial effects in at least two-dimensions must be included due to the inherent spatial variation of mechanical stimuli relevant to perfusion bioreactors, most notably, fluid shear stress, a feature not captured in the long-wavelength limit.
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spelling nottingham-290492020-05-04T20:25:05Z https://eprints.nottingham.ac.uk/29049/ The influence of bioreactor geometry and the mechanical environment on engineered tissues Osborne, J.M. O'Dea, Reuben D. Whiteley, J.P. Byrne, H.M. Waters, S.L. A three phase model for the growth of a tissue construct within a perfusion bioreactor is examined. The cell population (and attendant extracellular matrix), culture medium and porous scaffold are treated as distinct phases. The bioreactor system is represented by a two-dimensional channel containing a cell-seeded rigid porous scaffold (tissue construct) which is perfused with culture medium. Through the prescription of appropriate functional forms for cell proliferation and extracellular matrix deposition rates, the model is used to compare the influence of cell density-, pressure- and culture medium shear stress-regulated growth on the composition of the engineered tissue. The governing equations are derived in O'Dea \emph{et al.} (A multiphase model for tissue construct growth in a perfusion bioreactor, \emph{Math. Med. Biol.}, In press), in which the long-wavelength limit was exploited to aid analysis; here, finite element methods are used to construct two-dimensional solutions to the governing equations and to investigate thoroughly their behaviour. Comparison of the total tissue yield and averaged pressures, velocities and shear stress demonstrates that quantitative agreement between the two-dimensional and long-wavelength approximation solutions is obtained for channel aspect ratios of order $10^{-2}$ and that much of the qualitative behaviour of the model is captured in the long-wavelength limit, even for relatively large channel aspect ratios. However, we demonstrate that in order to capture accurately the effect of mechanotransduction mechanisms on tissue construct growth, spatial effects in at least two-dimensions must be included due to the inherent spatial variation of mechanical stimuli relevant to perfusion bioreactors, most notably, fluid shear stress, a feature not captured in the long-wavelength limit. American Society of Mechanical Engineers 2010-05 Article PeerReviewed Osborne, J.M., O'Dea, Reuben D., Whiteley, J.P., Byrne, H.M. and Waters, S.L. (2010) The influence of bioreactor geometry and the mechanical environment on engineered tissues. Journal of Biomechanical Engineering, 132 (5). 051006/1-051006/12. ISSN 0148-0731 http://biomechanical.asmedigitalcollection.asme.org/article.aspx?articleid=1475884 doi:10.1115/1.4001160 doi:10.1115/1.4001160
spellingShingle Osborne, J.M.
O'Dea, Reuben D.
Whiteley, J.P.
Byrne, H.M.
Waters, S.L.
The influence of bioreactor geometry and the mechanical environment on engineered tissues
title The influence of bioreactor geometry and the mechanical environment on engineered tissues
title_full The influence of bioreactor geometry and the mechanical environment on engineered tissues
title_fullStr The influence of bioreactor geometry and the mechanical environment on engineered tissues
title_full_unstemmed The influence of bioreactor geometry and the mechanical environment on engineered tissues
title_short The influence of bioreactor geometry and the mechanical environment on engineered tissues
title_sort influence of bioreactor geometry and the mechanical environment on engineered tissues
url https://eprints.nottingham.ac.uk/29049/
https://eprints.nottingham.ac.uk/29049/
https://eprints.nottingham.ac.uk/29049/