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We present a simplified two-dimensional model of fluid flow, solute transport, and cell distribution in a hollow fibre membrane bioreactor. We consider two cell populations, one undifferentiated and one differentiated, with differentiation stimulated either by growth factor alone, or by both growth factor and fluid shear stress. Two experimental configurations are considered, a 3-layer model in which the cells are seeded in a scaffold throughout the extracapillary space (ECS), and a 4-layer model in which the cell-scaffold construct occupies a layer surrounding the outside of the hollow fibre, only partially filling the ECS. Above this is a region of free-flowing fluid, referred to as the upper fluid layer. Following previous models by the authors (Pearson et al. in Math Med Biol, 2013, Biomech Model Mechanbiol 1-16, 2014a, we employ porous mixture theory to model the dynamics of, and interactions between, the cells, scaffold, and fluid in the cell-scaffold construct. We use this model to determine operating conditions (experiment end time, growth factor inlet concentration, and inlet fluid fluxes) which result in a required percentage of differentiated cells, as well as maximising the differentiated cell yield and minimising the consumption of expensive growth factor.

Original publication

DOI

10.1007/s10237-015-0717-6

Type

Journal article

Journal

Biomech Model Mechanobiol

Publication Date

06/2016

Volume

15

Pages

683 - 700

Keywords

Asymptotic reduction, Cell differentiation, Chemical stimulation, Fluid shear, Multiphase flow, Tissue engineering, Animals, Bioreactors, Cell Differentiation, Cell Proliferation, Humans, Intercellular Signaling Peptides and Proteins, Models, Biological, Numerical Analysis, Computer-Assisted, Stress, Mechanical, Time Factors