WEB Hydrodynamics of microcarrier suspensions in stirred-tank bioreactors for stem cell proliferation – Principles and challenges
The potential applications of stem cells in medicine are very promising but usual cell cultures methods (T-Flasks) do not provide sufficient amounts for clinical studies nor clinical application. Upscaling and automation of the process will be required in the near future to ensure reproducibility and quality of the cell acquisition process. The most promising expansion technique to date is based on the use of spherical particles, the so-called microcarriers, on which the cells multiply, suspended in a stirred tank bioreactor. However, some challenges have to be overcome, including the understanding and the control of the hydrodynamics generated in the vessel by mechanical agitation.
For optimum growth, the microcarriers need to be suspended to ensure medium homogenization and avoid microcarrier aggregation, while limiting the power input to avoid mechanical stresses due to (1) liquid-solid interaction (shear stress) and to (2) solid-solid interactions (collisions between particles and collisions between particles and walls). Such hydromechanical stresses could damage the cells attached on microcarriers or altered their quality.
Still today, stirred tank bioreactor for stem cell cultures are usually operated at the just-suspended agitation rate NJs i.e. at the minimal agitation rate needed to suspend all the particles. However, this criterion is not sufficient to characterize neither the spatial distribution of microcarriers inside the bioreactor nor the mechanical stresses encountered by the cells. On one hand, the impeller and bioreactor design have a significant impact on the just-suspended agitation rate, the solid spatial distribution, as well as on the power input and thus the hydromechanical stresses. On the other hand, the microcarrier properties, especially the size and density, have also an influence on the suspension state and on the mechanical stresses arising from the collisions.