Modelling Stirred Suspension Bioreactors for Scalable Expansion of Pluripotent Stem Cells

Date
2018-06-25
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Abstract
The emerging field of regenerative medicine seeks to leverage the potential of stem cell therapies to treat a wide variety of diseases and conditions. Sophisticated bioprocesses with engineering controls are required to produce the billions of cells required to facilitate these therapies. To this end, computational fluid dynamics (CFD) has been gaining popularity as a tool to characterize the hydrodynamic environment stem cells experience during bioprocessing. Recent studies have shown mammalian stem cell cultures have non-Newtonian viscosity, while CFD investigations of mammalian stem cell bioprocessing have assumed they are a Newtonian fluid. This study compares CFD simulations of 100mL and 500mL stirred suspension bioreactors with Newtonian and non-Newtonian viscosity models. Findings indicate shear stress, turbulent energy dissipation rate, power number, and turbulent power ratio are all significantly affected by the difference in viscosity models. Further, volume average turbulent energy dissipation rate from CFD studies with non-Newtonian viscosity was used to successfully maintain murine embryonic stem cell aggregate size distribution during bioreactor scale-up. The results of this study demonstrate the need for accurate representation of cell culture viscosity and highlight the power of CFD as a tool to control and optimize stem cell bioprocessing.
Description
Keywords
Bioreactor, CFD, Stem Cell, Aggregate, Rheology, Population Balance, Scale-Up
Citation
Wyma, A. A. (2018). Modelling Stirred Suspension Bioreactors for Scalable Expansion of Pluripotent Stem Cells (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32344