Scaling-Up Vertical Wheel Bioreactors Based on Cell Aggregate Exposure to Shear Stress and Energy Dissipation Rate

This publication investigates hydrodynamic scale-up of human pluripotent stem cell aggregate cultures in 100 and 500 mL Vertical-Wheel bioreactors. Three-dimensional transient flow simulations were performed at multiple agitation rates, and trajectories were calculated for aggregates ranging from 200 to 1,000 micrometers. Shear stress and energy dissipation rate exposure histories were compared with aggregation efficiency, cell counts, aggregate size, and expansion measured during six-day cultures. Results showed that aggregate size, agitation, and vessel scale influence trajectory-based exposure in ways not fully represented by maximum or volume-average metrics. Energy dissipation exposure was associated with aggregation efficiency, cell number, aggregate size, and total fold expansion. Under the tested conditions, shear stress did not significantly affect hPSC aggregation or proliferation. The study proposes trajectory-based energy dissipation exposure as a more representative scale-up parameter.