Journal of Artificial Organs

, Volume 17, Issue 4, pp 329–336 | Cite as

Applying shear stress to endothelial cells in a new perfusion chamber: hydrodynamic analysis

  • Fatemeh Anisi
  • Nasim Salehi-Nik
  • Ghassem Amoabediny
  • Behdad Pouran
  • Nooshin Haghighipour
  • Behrouz Zandieh-Doulabi
Original Article Tissue Engineering / Regenerative Medicine


Perfusion bioreactors have been proved to be an impartible part of vascular tissue engineering due to its broad range of applications as a means to distribute nutrients within porous scaffold along with providing appropriate physical and mechanical stimuli. To better understand the mechanical phenomena inside a bioreactor, computational fluid dynamics (CFD) was adopted followed by a validation technique. The fluid dynamics of the media inside the bioreactor was modeled using the Navier–Stokes equation for incompressible fluids while convection through the scaffold was described by Brinkman’s extension of Darcy’s law for porous media. Flow within the reactor determined the orientation of endothelial cells on the scaffold. To validate flow patterns, streamlines and shear stresses, colorimetry technique was used following attained results from CFD. Our bioreactor was modeled to simulate the optimum condition and flow patterns over scaffold to culture ECs for in vitro experimentation. In such experiments, cells were attached firmly without significant detachment and more noticeably elongation process was triggered even shortly after start up.


Computational fluid dynamics (CFD) Perfusion bioreactor Shear stress Colorimetry Endothelial cells (ECs) 


  1. 1.
    Jaasma MJ, Plunkett NA, O’Brien FJ. Design and validation of a dynamic flow perfusion bioreactor for use with compliant tissue engineering scaffolds. J Biotechnol. 2008;133:490–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Ku DN. Blood flow in arteries. Annu Rev Fluid Mech. 1997;29:399–434.CrossRefGoogle Scholar
  3. 3.
    Lawrence BJ, Devarapalli M, Madihally SV. Flow dynamics in bioreactors containing tissue engineering scaffolds. Biotechnol Bioeng J. 2009;102:935–47.CrossRefGoogle Scholar
  4. 4.
    Min Leong Ch, Wei T, Nackman G. In vitro measurement of pulsatile flow over endothelial cells. Am Phys Soc. 2006: 28–31.Google Scholar
  5. 5.
    Whittaker RJ, Booth R, Dyson R, Bailey C, Chini LP, Naire Sh, Payvandi S, Rong Z, Woollard H, Cummings LJ, Waters SL, Mawasse L, Chaudhuri JB, Ellis MJ, Michael V, Kuiper NJ, Cartmell S. Mathematical modeling of fiber-enhanced perfusion inside a tissue-engineering bioreactor. J Theor Biol. 2009;256:533–46.PubMedCrossRefGoogle Scholar
  6. 6.
    Jungreuthmayer C, Jaasma MJ, Al-Munajjed AA, Zanghellini J, Kelly DJ, O’Brien FJ. Deformation simulation of cells seeded on a collagen-GAG scaffold in a flow perfusion bioreactor using a sequential 3D CFD-elastostatics model. Med Eng Phys. 2009;31:420–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Fisher AB, Chien S, Barakat AI, Nerem RM. Endothelial cellular response to altered shear stress. Am J Physiol Lung Cell Mol Physiol. 2001;281:529–33.Google Scholar
  8. 8.
    Davies PF, Mundel T, Barbee KA. A mechanism for heterogeneous endothelial responses to flow in vivo and in vitro. J Biomech. 1995;28:1553–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Ohashi T, Sato M. Remodeling of vascular endothelial cells exposed to fluid shearstress: experimental and numerical approach. Fluid Dyn Res. 2005;37:40–59.CrossRefGoogle Scholar
  10. 10.
    Davies PF, Remuzzi A, Gordon EJ, Dewey CF Jr, Gimbrone MA Jr. Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc Nat Acad Sci USA. 1986;83:2114–7.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    RJ Allen D, Bogle, Ridley AJ. Modelling morphological change in endothelial cells induced by shear stress. 16th European Symp on Computer Aided Process Eng. 2006: 1723–1728.Google Scholar
  12. 12.
    Traub O, Berk B. Laminar shear stress mechanisms by which endothelial cells transduce an atheroprotective force. Arterioscler Thromb Vasc Biol. 1998;18:677–85.PubMedCrossRefGoogle Scholar
  13. 13.
    Dewey CF Jr, Bussolari SR, Gimbrone MA Jr, Davies PF. The dynamic response of vascular endothelial cells to fluid shear stress. J Biomech Eng. 1981;103:177–85.PubMedCrossRefGoogle Scholar
  14. 14.
    Chisti Y. Hydrodynamic damage to animal cells. Crit Rev Biotechnol. 2001;21:67–110.PubMedCrossRefGoogle Scholar
  15. 15.
    Lacolley P. Mechanical influence of cyclic stretch on vascular endothelial cells. Cardiovasc Res. 2004;63:577–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Papaioannou TG, Stefanadis C. Vascular wall shear stress: basic principles and methods. Hellenic J Cardiol. 2005;46:9–15.PubMedGoogle Scholar
  17. 17.
    Porter B, Zauel R, Stockman H, Guldberg R, Fyhrie D. 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. J Biomech. 2005;38:543–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Gerald FY. A manual of physiology. Philadelphia: P. Blakiston; 1890.Google Scholar
  19. 19.
    Truskey GA, Yuan F, Katz DF. Transport phenomena in biological systems. 3rd ed. Upper Saddle River: Pearson Prentice-Hall; 2004.Google Scholar
  20. 20.
    Chung CA, Chen CP, Lin TH, Tseng CS. A compact computational model for cell constructs development in perfusion culture. Biotechnol Bioeng J. 2008;99:1535–41.CrossRefGoogle Scholar
  21. 21.
    Coletti F, Macchietto S, Elvassore N. Mathematical modeling of three-dimensional cell cultures in perfusion bioreactors. Ind Eng Chem Res. 2006;45:8158–69.CrossRefGoogle Scholar
  22. 22.
    Chung CA, Chen CW, Tseng CS. Enhancement of cell growth in tissue-engineering constructs under direct perfusion: modeling and simulation. Biotechnol Bioeng J. 2007;97:1603–16.CrossRefGoogle Scholar
  23. 23.
    Aloi LE, Cherry RS. Cellular response to agitation characterized by energy dissipation at the impeller tip. Chem Eng Sci. 1996;51:1523–9.CrossRefGoogle Scholar
  24. 24.
    Li YJ, Hoga J, Chien Sh. Molecular basis of the effects of shear stress on vascular endothelial cells. J of Biomech. 2005;38:1949–71.CrossRefGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2014

Authors and Affiliations

  • Fatemeh Anisi
    • 1
    • 2
    • 5
  • Nasim Salehi-Nik
    • 1
    • 2
  • Ghassem Amoabediny
    • 1
    • 2
  • Behdad Pouran
    • 1
    • 2
    • 6
  • Nooshin Haghighipour
    • 3
  • Behrouz Zandieh-Doulabi
    • 4
  1. 1.Department of Chemical Engineering, Faculty of EngineeringUniversity of TehranTehranIran
  2. 2.Department of Biomedical Engineering, Research Center for New Technologies in Life Science EngineeringUniversity of TehranTehranIran
  3. 3.National Cell BankPasteur Institute of IranTehranIran
  4. 4.Department of Oral Cell BiologyAcademic Centre for Dentistry Amsterdam-Universiteit van Amsterdam and Vrije UniversiteitAmsterdamThe Netherlands
  5. 5.Department of Process and Energy, Faculty of 3MEDelft University of TechnologyDelftThe Netherlands
  6. 6.Department of OrthopaedicsUMC UtrechtUtrechtThe Netherlands

Personalised recommendations