Optimal metabolite transport in hollow fibre membrane bioreactors

Abstract

Hollow fibre membrane bioreactors provide a fast and efficient method for engineering functional tissue for use in medical treatments. Flow is utilised to overcome mass transport limitations by perfusing a nutrient-rich culture medium through the fibre lumen, which can then transport along the fibre lumen or across the porous membrane wall. Cells seeded at the outer membrane wall consume the nutrient and subsequently produce waste metabolites, which are transported away through an external extra-capillary space (ECS) along with excess nutrient. We present and investigate a two-dimensional axisymmetric model for fluid flow and solute transport through a single-fibre bioreactor configuration, with cells seeded to the external fibre wall. Fluid flow is modelled by steady lubrication and Darcy equations, which are coupled to the solute transport problem modelled by a system of advection–diffusion equations, supplemented with a reaction term to model the cell layer. Our model analysis reveals how spatially varying wall permeability distributions can be utilised to provide uniform nutrient delivery to a spatially uniform, homogeneous cell population. We also reveal how maximising the transmural pressure drop across the membrane wall is the dominant mechanism for waste removal rather than traditional experimental methods of flushing the ECS.