A computational analysis of the impact of mass transport and shear on three-dimensional stem cell cultures in perfused micro-bioreactors

In this study, Computational Fluid Dynamics (CFD) is used to investigate and compare the impact of bioreactor parameters (such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell (hMSC) expansion. The geometric characteristics of the TissueFlex® (Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate (in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium (DMEM), supplied at two inlet flow rates of 25 and 100 μl·h^{- 1}, was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to hMSC growth and expansion. Furthermore, results indicated that the 'top-inout' design (as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate (25 μl·h^{- 1}), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.