Abstract Summary (Max 250 words)
In vitro cultivation of human inducible pluripotent stem cells (hiPSCs) for the production of Red Blood cells (RBCs) is a promising therapeutic alternative to donor-based blood cell transfusions. The sensitivity of human stem cell aggregates requires a tight balance between hydrodynamic stresses and suspension of the 3D aggregates, while maintaining sufficient oxygen transfer. We performed CFD-DEM simulations to characterize a 250 mL MiniBio® bioreactor for shear sensitive microcarrier cultures. Our model uses the Lattice Boltzmann method with a large eddy simulation (LES) turbulence model to solve the fluid flow, combined with a discrete element method (DEM) for microcarrier particle motion. We extensively validated our simulations using mixing time, kLa, and just-suspension (Njs) experiments, demonstrating that our model can predict these engineering parameters with a 20% accuracy. Additionally, 4D-particle tracking velocimetry measurements showed a good agreement between measured and predicted particle velocity and acceleration profiles. Inclusion of the Hertzian particle-particle interactions was essential to correctly capture particle suspension behaviour. The validated model was used to study the influence of important operating conditions, including stirrer speed, pumping-mode, stirrer height and filling volume. Furthermore, the Lagrangian nature of the simulated microcarriers was used to characterize the spatial-temporal fluctuations in fluid strain and energy dissipation rate from the microcarrier perspective to quantify the hydrodynamic stresses on microcarriers for different operating conditions. Future work will focus on applying this model to a 3L bioreactor and will help accelerating the scale-up of shear-sensitive stem-cell microcarrier cultures.
