Biomechanics and Modeling in Mechanobiology

, Volume 10, Issue 4, pp 565–576 | Cite as

A dynamical study of the mechanical stimuli and tissue differentiation within a CaP scaffold based on micro-CT finite element models

Original Paper


The control of the mechanical stimuli transmitted to the cells is critical for the design of functional scaffolds for tissue engineering. The objective of this study was to investigate the dynamics of the mechanical stimuli transmitted to the cells during tissue differentiation in an irregular morphology scaffold under compressive load and perfusion flow. A calcium phosphate-based glass porous scaffold was used. The solid phase and the fluid flow within the pores were modeled as linear elastic solid material and Newtonian fluid, respectively. In the fluid model, different levels of viscosity were used to simulate tissue differentiation. Compressive strain of 0.5% and fluid flow with constant inlet velocity of 10 μm/s or constant inlet pressure of 3 Pa were applied. Octahedral shear strain and fluid shear stress were used as mechano-regulatory stimuli. For constant inlet velocity, stimuli equivalent to bone were predicted in 80% of pore volume for the case of low tissue viscosity. For the cases of high viscosity, fluctuations between stimuli equivalent to tissue formation and cell death were predicted due to the increase in the fluid shear stress when tissue started to fill pores. When constant pressure was applied, stimuli equivalent to bone were predicted in 62% of pore volume when low tissue viscosity was used and 42% when high tissue viscosity was used. This study predicted critical variations of fluid shear stress when cells differentiated. If these variations are not controlled in vitro, they can impede the formation of new matured tissue.


Tissue engineering Calcium phosphate Mechanoregulation Micro computed tomography Finite element modeling 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Byrne DP, Lacroix D, Planell JA, Kelly DJ, Prendergast PJ (2007) Simulation of tissue differentiation in a scaffold as a function of porosity Young’s modulus and dissolution rate: application of mechanobiological models in tissue engineering. Biomaterials 28: 5544–5554CrossRefGoogle Scholar
  2. Carter DR, Beaupré GS (2001) Skeletal function and form. Cambridge university press, CambridgeGoogle Scholar
  3. Cartmell SH, Porter BD, Garcia AJ, Guldberg RE (2003) Effects of medium perfusion rate on cell-seeded three-dimensional bone constructs in vitro. Tissue Eng 9: 1197–1203CrossRefGoogle Scholar
  4. Checa S, Prendergast PJ (2010) Effect of cell seeding and mechanical loading on vascularization and tissue formation inside a scaffold: a mechano-biological model using a lattice approach to simulate cell activity. J Biomech 43: 961–968CrossRefGoogle Scholar
  5. Cioffi M, Boschetti F, Raimondi MT, Dubini G (2006) Modeling evaluation of the fluid-dynamic microenvironment in tissue-engineered constructs: a micro-CT based model. Biotechnol Bioeng 93: 500–510CrossRefGoogle Scholar
  6. Glowacki J, Trepman E, Folkman J (1983) Cell shape and phenotypic expression in chondrocytes. Proc Soc Exp Biol Med 172: 93–98Google Scholar
  7. Holtorf HL, Sheffield TL, Ambrose CG, Jansen AJ, Mikos AG (2005) Flow perfusion culture of marrow stromal cells seeded on porous biphasic calcium phosphate ceramics. Ann Biomed Eng 33: 1238–1248CrossRefGoogle Scholar
  8. Isaksson H, Wilson W, van Donkelaar CC, Huiskes R, Ito K (2006) Comparison of biophysical stimuli for mechano-regulation of tissue differentiation during fracture healing. J Biomech 39: 1507–1516CrossRefGoogle Scholar
  9. Kelly DJ, Prendergast PJ (2006) Prediction of the optimal mechanical properties for a scaffold used in osteochondral defect repair. Tissue Eng 12: 1509–2519Google Scholar
  10. Lacroix D, Château A, Ginebra MP, Planell JA (2006) Micro-finite element models of bone tissue-engineering scaffolds. Biomaterials 27: 5326–5334CrossRefGoogle Scholar
  11. Lacroix D, Planell JA, Prendergast PJ (2009) Computer-aided design and finite-element modelling of biomaterial scaffolds for bone tissue engineering. Phil Trans R Soc A 367: 1993–2009MATHCrossRefGoogle Scholar
  12. Lacroix D, Prendergast PJ, Li G, Marsh D (2002) Biomechanical model to simulate tissue differentiation and bone regeneration: application to fracture healing. Med Biol Eng Comput 40: 14–21CrossRefGoogle Scholar
  13. Lesman A, Blinder Y, Levenberg S (2010) Modeling of flow-induced shear stress applied on 3D cellular scaffolds: implications for vascular tissue engineering. Biotechnol Bioeng 105: 645–654CrossRefGoogle Scholar
  14. Maes F, Van Ransbeeck P, Van Oosterwyck H, Verdonck P (2009) Modeling fluid flow through irregular scaffolds for perfusion bioreactors. Biotechnol Bioeng 103: 621–630CrossRefGoogle Scholar
  15. Martin I, Wendt D, Heberer M (2004) The role of bioreactors in tissue engineering. Trends Biotechnol 22: 80–86CrossRefGoogle Scholar
  16. Milan JL, Planell JA, Lacroix D (2009) Computational modelling of the mechanical environment of osteogenesis within a polylactic acid–calcium phosphate glass scaffold. Biomaterials 30: 4219–4226CrossRefGoogle Scholar
  17. Navarro M, Michiardi A (2008) The challenge of combining cells, synthetic materials and growth factors to engineer bone tissue. In: Barnes SJ, Harris LP (eds) Tissue engineering: roles, materials and applications. Novapublishers, New York, pp 19–66Google Scholar
  18. Olivares A, Marsal E, Planell JA, Lacroix D (2009) Finite element study of scaffold architecture design and culture conditions for tissue engineering. Biomaterials 30: 6142–6149CrossRefGoogle Scholar
  19. Porter B, Zauel R, Stockman H, Guldberg R, Fyhrie D (2005) 3-D computational modeling of media flow through scaffolds in a perfusion bioreactor. J Biomech 38: 543–549CrossRefGoogle Scholar
  20. Potier E, Noailly J, Ito K (2010) Directing bone marrow-derived stromal cell function with mechanics. J Biomech 43: 807–817CrossRefGoogle Scholar
  21. Prendergast PJ, Huiskes R, Søballe K (1997) Biophysical stimuli on cells during tissue differentiation at implant interfaces. J Biomech 30: 539–548CrossRefGoogle Scholar
  22. Raimondi MT, Moretti M, Cioffi M, Giordano C, Boschetti F, Lagana K, Pietrabissa R (2006) The effect of hydrodynamic shear stress on 3D engineered chondrocyte systems subject to direct perfusion. Biorheol 43: 215–222Google Scholar
  23. Sandino C, Checa S, Prendergast PJ, Lacroix D (2010) Simulation of angiogenesis and cell differentiation in a CaP scaffold subjected to compressive load strains using a lattice modeling approach. Biomaterials 31: 2446–2452CrossRefGoogle Scholar
  24. Sandino C, Planell JA, Lacroix D (2008) A finite element study of mechanical stimuli in scaffolds for bone tissue engineering. J Biomech 41: 1005–1014CrossRefGoogle Scholar
  25. Sikavitsas VI, Temenoff JS, Mikos AG (2001) Biomaterials and Bone mechanotransduction. Biomaterials 22: 2581–2593CrossRefGoogle Scholar
  26. Stops AJF, Heraty KB, Browne M, O’Brien FJ, McHugh PE (2010) A prediction of cell differentiation and proliferation within a collagen-glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow. J Biomech 43: 618–626CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Institute for Bioengineering of CatalunyaBarcelonaSpain

Personalised recommendations