Multiphase modelling of the effect of fluid shear stress on cell yield and distribution in a hollow fibre membrane bioreactor.

We present a simplified two-dimensional model of fluid flow, nutrient transport and cell distribution in a hollow fibre membrane bioreactor, with the aim of exploring how fluid flow can be used to control the distribution and yield of a cell population which is sensitive to both fluid shear stress and nutrient concentration. The cells are seeded in a scaffold in a layer on top of the hollow fibre, only partially occupying the extracapillary space. Above this layer is a region of free-flowing fluid which we refer to as the upper fluid layer. The flow in the lumen and upper fluid layer is described by the Stokes equations, whilst the flow in the porous fibre membrane is assumed to follow Darcy's law. Porous mixture theory is used to model the dynamics of and interactions between the cells, scaffold and fluid in the cell-scaffold construct. The concentration of a limiting nutrient (e.g. oxygen) is governed by an advection-reaction-diffusion equation in each region. Through exploitation of the small aspect ratio of each region and asymptotic analysis, we derive a coupled system of partial differential equations for the cell volume fraction and nutrient concentration. We use this model to investigate the effect of mechanotransduction on the distribution and yield of the cell population, by considering cases in which cell proliferation is either enhanced or limited by fluid shear stress and by varying experimentally controllable parameters such as flow rate and cell-scaffold construct thickness.