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

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 bi...

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Autores principales: Lloyd A C Chapman, Rebecca J Shipley, Jonathan P Whiteley, Marianne J Ellis, Helen M Byrne, Sarah L Waters
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Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/e8d7f704587d42848b1366cb2516c3ab
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spelling oai:doaj.org-article:e8d7f704587d42848b1366cb2516c3ab2021-11-25T06:03:11ZOptimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.1932-620310.1371/journal.pone.0105813https://doaj.org/article/e8d7f704587d42848b1366cb2516c3ab2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25157635/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Lloyd A C ChapmanRebecca J ShipleyJonathan P WhiteleyMarianne J EllisHelen M ByrneSarah L WatersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e105813 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lloyd A C Chapman
Rebecca J Shipley
Jonathan P Whiteley
Marianne J Ellis
Helen M Byrne
Sarah L Waters
Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
description 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.
format article
author Lloyd A C Chapman
Rebecca J Shipley
Jonathan P Whiteley
Marianne J Ellis
Helen M Byrne
Sarah L Waters
author_facet Lloyd A C Chapman
Rebecca J Shipley
Jonathan P Whiteley
Marianne J Ellis
Helen M Byrne
Sarah L Waters
author_sort Lloyd A C Chapman
title Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
title_short Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
title_full Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
title_fullStr Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
title_full_unstemmed Optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
title_sort optimising cell aggregate expansion in a perfused hollow fibre bioreactor via mathematical modelling.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/e8d7f704587d42848b1366cb2516c3ab
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