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Mathematical modelling of a liver hollow fibre bioreactor

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journal contribution
posted on 2019-05-21, 08:32 authored by Ian Sorrell, Rebecca Shipley, Sophie Regan, Iain Gardner, Michael P. Storm, Marianne J. Ellis, John WardJohn Ward, Dominic P. Williams, Pratibha Mistry, Jose D. Salazar, Andrew Scott, Steven Webb
A mathematical model has been developed to assist with the development ofa hollow fibre bioreactor (HFB) forhepatotoxicity testing of xenobiotics; specifically, to informthe HFBoperating set-up, interpret data from HFB outputsand aid in optimizingHFBdesign to mimic certain hepatic physiological conditions. Additionally,the mathematical model has been used to identify the key HFB and compound parameters that will affect xenobiotic clearance. The analysis of this model has produced novel results that allow the operating set-up to be calculated,and predictions of compound clearanceto begenerated.The mathematical modelpredictsthe inlet oxygen concentration and volumetric flow ratethat gives a physiological oxygen gradient in the HFB to mimic a liver sinusoid. It has also been used to predict the concentration gradients and clearanceof a test drug and paradigm hepatotoxin, paracetamol (APAP).The effect of altering theHFBdimensions and fibre propertieson APAP clearance under the condition of a physiological oxygen gradientis analysed.These theoretical predictions can be usedto design the most appropriateexperimental set upand data analysis toquantitatively compare the functionality of cell types that are cultured within the HFB to those in other systems

Funding

The work was supported by the National Centrefor the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) CRACK-IT fund, Challenge 5: IVIVE.

History

School

  • Science

Department

  • Mathematical Sciences

Published in

Journal of Theoretical Biology

Volume

475

Pages

25 - 33

Citation

SORRELL, I. ... et al., 2019. Mathematical modelling of a liver hollow fibre bioreactor. Journal of Theoretical Biology, 475, pp.25-33.

Publisher

© Elsevier BV

Version

  • AM (Accepted Manuscript)

Publisher statement

This paper was accepted for publication in the journal Journal of Theoretical Biology and the definitive published version is available at https://doi.org/10.1016/j.jtbi.2019.05.008.

Acceptance date

2019-05-13

Publication date

2019-05-14

ISSN

0022-5193

Language

  • en

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