Morley, E.J., Brockett, C.L. orcid.org/0000-0002-6664-7259 and Verbruggen, S.W. (2024) Analytical and computational studies predict negligible risk of cell death from eddy generation off flat surfaces in cell culture flow systems. Frontiers in Bioengineering and Biotechnology, 12. 1340653. ISSN 2296-4185
Abstract
Cell-based therapies represent the current frontier of biomedical innovations, with the technologies required underpinning treatments as broad as CAR-T cell therapies, stem cell treatments, genetic therapies and mRNA manufacture. A key bottleneck in the manufacturing process for each of these lies in the expansion of cells within a bioreactor vessel, requiring by far the greatest share of time for what are often time-critical therapies. While various designs, culture feeding and mixing methods are employed in these bioreactors, a common concern among manufacturers and researchers lies in whether shear stresses generated by culture media flow will damage cells and inhibit expansion. This study develops an analytical tool to link macro-scale measures of flow to risk of cell death using relationships with eddy size and dissipation rates, from eddies generated off flat surfaces. This analytical tool was then employed using computational fluid dynamics (CFD) to replicate a range of generic bioreactor geometries and flow conditions. We found that no combination of flow condition or design parameter was predicted by the tool to cause cell death within eddies, indicating negligible risk of cell death due to eddy formation within cell culture systems. While this requires experimental validation, and does not apply when cells are expanded using microcarriers, this tool nonetheless provides reassurance and accessible prediction of bioreactor design parameters that could result in cell death. Finally, our findings show that bioreactor design can be tailored such that the shear stress stimulation of cells can be selectively altered through small changes in flow rate.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 Morley, Brockett and Verbruggen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. http://creativecommons.org/licenses/by/4.0/ |
Keywords: | cell culture therapy; fluid shear stress; eddy formation; microfluidics; T cell bioreactor; Reynolds number |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Mechanical Engineering (Sheffield) |
Funding Information: | Funder Grant number European Commission 748305 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Aug 2024 11:17 |
Last Modified: | 29 Aug 2024 11:17 |
Status: | Published |
Publisher: | Frontiers Media SA |
Refereed: | Yes |
Identification Number: | 10.3389/fbioe.2024.1340653 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:216507 |