Computational Fluid Dynamic Characterization Of Vertical-Wheel Bioreactors Used For Effective Scale-Up Of hiPSC Aggregate Culture

By Tiffany Dang, Breanna S. Borys, Shivek Kanwar, James Colter, Hannah Worden, Abigail Blatchford, Matthew S. Croughan, Tareq Hossan, Derrick E. Rancourt, Brian Lee, Michael S. Kallos, Sunghoon Jung

Explore the use of computational fluid dynamics (CFD) modeling to characterize and optimize vertical-wheel (VW) bioreactors for the large-scale expansion of human-induced pluripotent stem cells (hiPSCs). Since iPSCs are highly sensitive to hydrodynamic forces, effective scale-up strategies are crucial for maintaining cell viability, proliferation, and uniformity. The study models four VW bioreactor scales (0.1 L, 0.5 L, 3 L, and 15 L), analyzing key parameters such as velocity, energy dissipation rate (EDR), and shear stress.

The CFD simulations reveal that VW bioreactors produce uniform hydrodynamic force distributions, minimizing shear stress while maintaining effective mixing. By establishing scale-up correlation equations, the study provides a method for predicting agitation rates across different bioreactor sizes while maintaining constant volume-average EDR. Experimental validation at the 0.1 L and 0.5 L scales confirms that the suggested agitation ranges lead to high cell expansion, healthy aggregate formation, and consistent growth. The research also highlights the importance of maintaining appropriate aggregate sizes to prevent necrosis and improve downstream processing.

Additionally, the study compares experimental and CFD-predicted power numbers, showing strong correlation, further validating the accuracy of the modeling approach. The findings demonstrate that VW bioreactors provide an optimal, scalable platform for iPSC culture, supporting applications in regenerative medicine, disease modeling, and drug discovery. By integrating CFD modeling with experimental validation, this study establishes a robust framework for bioreactor scale-up in cell therapy manufacturing.