Multiphase mixing characteristics in a microcarrier-based stirred tank bioreactor suitable for human mesenchymal stem cell expansion

Large-scale human mesenchymal stem cell expansion calls for a bioreaction system, that provides a sufficient growth surface. An alternative to static cultivations systems like cell factories are disposable stirred tank reactors. Here, microcarriers provide the required growth surface, but these make it difficult to achieve a complete homogenization in the bioreactor, while avoiding shear stress. To gain insight into this process, we investigated the impact of different power inputs (0.02-2.6 W m−3) on the mixing time (tm). Whereas tm was inversely proportional to agitation in a one-phase-system, aeration resulted in a constant mixing time at 30-70 rpm. A high microcarrier concentration (30 g L−1) and low stirrer speed (30 rpm) in the liquid-solid system caused a 50-fold increase in tm and the formation of a discrete non-mixed upper zone. The effect of the microcarrier concentration on tm became negligible at higher stirrer speeds. In the three-phase system, microcarrier settling was prevented by aeration and a minimal specific power input of 0.6 W m−3 was sufficient for complete homogenization. We confirmed that a low power input during stem cell expansion leads to inhomogeneity, which has not been investigated in the three-phase system up to date.