Tesis doctoral de Clara Inés Sandino Velásquez
Mechanical stimuli are one of the factors that affect cell differentiation in the process of bone tissue regeneration; therefore, in the development of scaffolds for tissue engineering, mechanical loads can be applied in order to induce cell activity. The specific mechanical stimuli transmitted to cells at a microscopic level when mechanical loads are applied can be studied using numerical techniques. The objective of this thesis was to study the mechanoregulation of tissue differentiation within calcium phosphate scaffolds using micro computed tomographed based finite element models. two samples of porous calcium phosphate based materials were used. Congruent finite element meshes, with the solid phase and the interconnected pores discretized, were developed in order to account for the scaffold irregular morphology. first, a study of the distribution of mechanical stimuli was performed. The solid phase and the fluid flow within the pores were modeled as linear elastic solid material and newtonian fluid respectively. Compressive strains of 0.5% of total deformation applied to the solid and interstitial fluid flows with inlet velocities of 1, 10 and 100 µm/s applied to the pores were simulated. Similar strain distributions for both materials were found, with compressive and tensile strain maximal values of 1.6% and 0.6% respectively. For the fluid flow models, the fluid velocity in some of the scaffold pores increased to 100 and 1000 times the inlet velocity. This study showed how mechanical loads and fluid flow applied to the scaffolds caused different levels of mechanical stimuli within the samples according to the morphology of the materials. next, a study of the mechanoregulation of tissue differentiation over time in a scaffold subjected to in vitro loads was performed. The solid phase and the fluid flow were modeled as in the study described above. 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 based on the theory of prendergast et al. (1997). When a constant velocity was simulated, 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 the pores. However, when constant pressure was applied, stimuli equivalent to bone formation were predicted in about half of the pore volume. These results suggest that in order to allow tissue differentiation within a scaffold, the fluid velocity should be decreased when tissue starts mineralizing. finally, a study of the angiogenesis and the mechanoregulation of tissue differentiation over time in a scaffold subjected to in vivo conditions was performed. Octahedral shear strain and relative fluid velocity were used as mechano-regulatory stimuli. The solid and pore phases were treated as poroelastic materials. Individual cell activity was simulated within the pore domain. Compressive strains of 0.5 and 1% of total deformation were simulated. Most vessels grew in the pores at the periphery of the scaffolds and were blocked by the scaffold walls. Similar capillary networks were formed independently of the magnitude of the mechanical strain applied. When 0.5% of strain was applied, 70% of the pore volume was affected by mechano-regulatory stimuli corresponding to bone formation; however, because of the lack of oxygen, only 40% of the volume was filled with osteoblasts. This study showed the effect of the lack of vascularization in the center of the scaffold on the tissue differentiation. such kind of studies, combined with in vitro studies, should contribute to the understanding of the process of tissue differentiation within the constructs and therefore to the improvement of scaffold design methods.
Datos académicos de la tesis doctoral «Simulatin of mechanoregulation and tissue differentiation in calcium phosphate scaffolds for tissue engineering«
- Título de la tesis: Simulatin of mechanoregulation and tissue differentiation in calcium phosphate scaffolds for tissue engineering
- Autor: Clara Inés Sandino Velásquez
- Universidad: Politécnica de catalunya
- Fecha de lectura de la tesis: 11/11/2010
Dirección y tribunal
- Director de la tesis
- Damien Lacroix
- Tribunal
- Presidente del tribunal: María pau Ginebra molins
- patrich Chabrand (vocal)
- ito Keita (vocal)
- patrick j. Prendergast (vocal)