Abstract
A 2D model is developed for fluid flow, mass transport and cell distribution in a hollow fibre membrane bioreactor. The geometry of the modelling region is simplified by excluding the exit ports at either end and focusing on the upper half of the central section of the bioreactor. Cells are seeded on a porous scaffold throughout the extracapillary space (ECS), and fluid pumped through the bioreactor via the lumen inlet and/or exit ports. In the fibre lumen and porous fibre wall, flow is described using Stokes and Darcy governing equations, respectively, while in the ECS porous mixture theory is used to model the cells, culture medium and scaffold. Reaction-advection-diffusion equations govern the concentration of a solute of interest in each region. The governing equations are reduced by exploiting the small aspect ratio of the bioreactor. This yields a coupled system for the cell volume fraction, solute concentration and ECS water pressure which is solved numerically for a variety of experimentally relevant case studies. The model is used to identify different regimes of cell behaviour, and results indicate how the flow rate can be controlled experimentally to generate a uniform cell distribution under regimes relevant to nutrient- and/or chemotactic-driven behaviours.
Highlights
In our society, there is an increasing need for replacement tissue and organs as a result of damage due to trauma, disease or old age
We focus on hollow fibre membrane bioreactors (HFMBs), which consist of a cylindrical, hollow glass module with an exit port at the up- and down-stream ends
We have developed a multiphase model of fluid flow, cell population evolution and solute transport in a simplified HFMB setup
Summary
There is an increasing need for replacement tissue and organs as a result of damage due to trauma, disease or old age. Tissue engineering is a promising alternative, as long as it has the potential to reduce these costs and improve patient prognoses. Since the patient’s own (autologous) cells are often used, there is a significantly reduced risk of rejection of the new tissue (Stock et al, 2001) This approach can be used as an alternative to artificial implants such as hip or knee replacements, which have a limited lifespan and can cause allergic reactions (Pörtner et al, 2005). The immense cost of even small-scale experiments has limited progress in the field to date, and prevented widespread scale-up for clinical use This is despite significant research being carried out: e.g. there are over 5600 PubMed articles from the last 15 years on cartilage tissue engineering alone, yet no routine clinical solutions. As a result of this, a vast array of bioreactor designs and materials exist, each needing a different set of operating conditions to successfully grow a particular tissue (Pörtner et al, 2005)
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