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ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.
Sec. Biomechanics
Volume 12 - 2024 | doi: 10.3389/fbioe.2024.1340653

Analytical and computational studies predict negligible risk of cell death from eddy generation off flat surfaces in cell culture flow systems

Provisionally accepted
Elliot J. Morley Elliot J. Morley 1,2Claire L. Brockett Claire L. Brockett 1,2Stefaan W. Verbruggen Stefaan W. Verbruggen 2,3,4*
  • 1 Department of Mechanical Engineering, Faculty of Engineering, The University of Sheffield, Sheffield, England, United Kingdom
  • 2 Insigneo Institute, Faculty of Engineering, The University of Sheffield, Sheffield, England, United Kingdom
  • 3 Queen Mary University of London, London, United Kingdom
  • 4 Centre for Predictive in Vitro Models, Faculty of Science and Engineering, Queen Mary University of London, London, England, United Kingdom

The final, formatted version of the article will be published soon.

    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 adherent 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 simulation of cells can be selectively altered through small changes in flow rate.

    Keywords: cell culture therapy, fluid shear stress, eddy formation, Microfluidics, T cell bioreactor, Reynolds number

    Received: 18 Nov 2023; Accepted: 24 Jul 2024.

    Copyright: © 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) or licensor 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.

    * Correspondence: Stefaan W. Verbruggen, Queen Mary University of London, London, United Kingdom

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.