SCI和EI收录∣中国化工学会会刊

Chinese Journal of Chemical Engineering ›› 2016, Vol. 24 ›› Issue (1): 163-174.DOI: 10.1016/j.cjche.2015.11.017

• 第25届中国过程控制会议专栏 • 上一篇    下一篇

A computational analysis of the impact of mass transport and shear on three-dimensional stem cell cultures in perfused micro-bioreactors

Himanshu Kaul1,2, Yiannis Ventikos3, Zhanfeng Cui1   

  1. 1 Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington, Oxford OX3 7DQ, UK;
    2 Department of Computer Science, University of Sheffield, Regent Court, Sheffield S1 4DP, UK;
    3 Department of Mechanical Engineering, University College London, Torrington Place, LondonWC1E 7JE, UK
  • 收稿日期:2015-03-20 修回日期:2015-07-03 出版日期:2016-01-28 发布日期:2016-02-23
  • 通讯作者: Zhanfeng Cui

A computational analysis of the impact of mass transport and shear on three-dimensional stem cell cultures in perfused micro-bioreactors

Himanshu Kaul1,2, Yiannis Ventikos3, Zhanfeng Cui1   

  1. 1 Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Old Road Campus Research Building, Headington, Oxford OX3 7DQ, UK;
    2 Department of Computer Science, University of Sheffield, Regent Court, Sheffield S1 4DP, UK;
    3 Department of Mechanical Engineering, University College London, Torrington Place, LondonWC1E 7JE, UK
  • Received:2015-03-20 Revised:2015-07-03 Online:2016-01-28 Published:2016-02-23
  • Contact: Zhanfeng Cui

摘要: In this study, Computational Fluid Dynamics (CFD) is used to investigate and compare the impact of bioreactor parameters (such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell (hMSC) expansion. The geometric characteristics of the TissueFlex® (Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate (in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium (DMEM), supplied at two inlet flow rates of 25 and 100 μl·h-1, was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to hMSC growth and expansion. Furthermore, results indicated that the ‘top-inout’ design (as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate (25 μl·h-1), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.

关键词: Alginate scaffolds, Bioreactors, Fluid mechanics, Dimensionless quantities, Mass transfer, Modelling, Perfusion

Abstract: In this study, Computational Fluid Dynamics (CFD) is used to investigate and compare the impact of bioreactor parameters (such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell (hMSC) expansion. The geometric characteristics of the TissueFlex® (Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate (in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium (DMEM), supplied at two inlet flow rates of 25 and 100 μl·h-1, was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to hMSC growth and expansion. Furthermore, results indicated that the ‘top-inout’ design (as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate (25 μl·h-1), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.

Key words: Alginate scaffolds, Bioreactors, Fluid mechanics, Dimensionless quantities, Mass transfer, Modelling, Perfusion