Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.

Handle URI:
http://hdl.handle.net/10754/596805
Title:
Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
Authors:
Chapman, Lloyd A C; Shipley, Rebecca J; Whiteley, Jonathan P; Ellis, Marianne J; Byrne, Helen M; Waters, Sarah L
Abstract:
The need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to 0:05 Pa are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges 2.75 x 10(-5) m(2) s(-1) to 3 x 10(-5) m(2) s(-1) (equivalent to 2.07 ml min(-1) to 2.26 ml min(-1)) and 1.077 x 10(5) Pa to 1.083 x 10(5) Pa (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells.
Citation:
Chapman LAC, Shipley RJ, Whiteley JP, Ellis MJ, Byrne HM, et al. (2014) Optimising Cell Aggregate Expansion in a Perfused Hollow Fibre Bioreactor via Mathematical Modelling. PLoS ONE 9: e105813. Available: http://dx.doi.org/10.1371/journal.pone.0105813.
Publisher:
Public Library of Science (PLoS)
Journal:
PLoS ONE
KAUST Grant Number:
KUK-C1-013-04
Issue Date:
26-Aug-2014
DOI:
10.1371/journal.pone.0105813
PubMed ID:
25157635
PubMed Central ID:
PMC4144904
Type:
Article
ISSN:
1932-6203
Sponsors:
The work is primarily supported by an EPSRC Life Sciences Interface Doctoral Training Centre grant from the University of Oxford (EP/F500394/1). HMB is supported by King Abdullah University of Science and Technology, Saudi Arabia (Award No. KUK-C1-013-04). SLW is funded by the EPSRC through an Advanced Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Full metadata record

DC FieldValue Language
dc.contributor.authorChapman, Lloyd A Cen
dc.contributor.authorShipley, Rebecca Jen
dc.contributor.authorWhiteley, Jonathan Pen
dc.contributor.authorEllis, Marianne Jen
dc.contributor.authorByrne, Helen Men
dc.contributor.authorWaters, Sarah Len
dc.date.accessioned2016-02-21T08:51:02Zen
dc.date.available2016-02-21T08:51:02Zen
dc.date.issued2014-08-26en
dc.identifier.citationChapman LAC, Shipley RJ, Whiteley JP, Ellis MJ, Byrne HM, et al. (2014) Optimising Cell Aggregate Expansion in a Perfused Hollow Fibre Bioreactor via Mathematical Modelling. PLoS ONE 9: e105813. Available: http://dx.doi.org/10.1371/journal.pone.0105813.en
dc.identifier.issn1932-6203en
dc.identifier.pmid25157635en
dc.identifier.doi10.1371/journal.pone.0105813en
dc.identifier.urihttp://hdl.handle.net/10754/596805en
dc.description.abstractThe need for efficient and controlled expansion of cell populations is paramount in tissue engineering. Hollow fibre bioreactors (HFBs) have the potential to meet this need, but only with improved understanding of how operating conditions and cell seeding strategy affect cell proliferation in the bioreactor. This study is designed to assess the effects of two key operating parameters (the flow rate of culture medium into the fibre lumen and the fluid pressure imposed at the lumen outlet), together with the cell seeding distribution, on cell population growth in a single-fibre HFB. This is achieved using mathematical modelling and numerical methods to simulate the growth of cell aggregates along the outer surface of the fibre in response to the local oxygen concentration and fluid shear stress. The oxygen delivery to the cell aggregates and the fluid shear stress increase as the flow rate and pressure imposed at the lumen outlet are increased. Although the increased oxygen delivery promotes growth, the higher fluid shear stress can lead to cell death. For a given cell type and initial aggregate distribution, the operating parameters that give the most rapid overall growth can be identified from simulations. For example, when aggregates of rat cardiomyocytes that can tolerate shear stresses of up to 0:05 Pa are evenly distributed along the fibre, the inlet flow rate and outlet pressure that maximise the overall growth rate are predicted to be in the ranges 2.75 x 10(-5) m(2) s(-1) to 3 x 10(-5) m(2) s(-1) (equivalent to 2.07 ml min(-1) to 2.26 ml min(-1)) and 1.077 x 10(5) Pa to 1.083 x 10(5) Pa (or 15.6 psi to 15.7 psi) respectively. The combined effects of the seeding distribution and flow on the growth are also investigated and the optimal conditions for growth found to depend on the shear tolerance and oxygen demands of the cells.en
dc.description.sponsorshipThe work is primarily supported by an EPSRC Life Sciences Interface Doctoral Training Centre grant from the University of Oxford (EP/F500394/1). HMB is supported by King Abdullah University of Science and Technology, Saudi Arabia (Award No. KUK-C1-013-04). SLW is funded by the EPSRC through an Advanced Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.publisherPublic Library of Science (PLoS)en
dc.rightsThis is an open-access article distributed under the terms of the , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.titleOptimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.en
dc.typeArticleen
dc.identifier.journalPLoS ONEen
dc.identifier.pmcidPMC4144904en
dc.contributor.institutionMathematical Institute, University of Oxford, Oxford, United Kingdom; Department of Computer Science, University of Oxford, Oxford, United Kingdom.en
dc.contributor.institutionDepartment of Mechanical Engineering, UCL, London, United Kingdom.en
dc.contributor.institutionDepartment of Computer Science, University of Oxford, Oxford, United Kingdom.en
dc.contributor.institutionDepartment of Chemical Engineering, University of Bath, Bath, United Kingdom.en
dc.contributor.institutionMathematical Institute, University of Oxford, Oxford, United Kingdom.en
kaust.grant.numberKUK-C1-013-04en

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