Jean-Louis Milan

Computational modelling of the mechanical environment of osteogenesis within a polylactic acid–calcium phosphate glass scaffold

A computational model based on finite element method (FEM) and computational fluid dynamics (CFD) is developed to analyse the mechanical stimuli in a composite scaffold made of polylactic acid (PLA) matrix with calcium phosphate glass (Glass) particles. Different bioreactor loading conditions were simulated within the scaffold. In vitro perfusion conditions were reproduced in the model. Dynamic compression was also reproduced in an uncoupled fluid-structure scheme: deformation level was studied analyzing the mechanical response of scaffold alone under static compression while strain rate was studied considering the fluid flow induced by compression through fixed scaffold. Results of the model show that during perfusion test an inlet velocity of 25 microm/s generates on scaffold surface a fluid flow shear stress which may stimulate osteogenesis. Dynamic compression of 5% applied on the PLA-Glass scaffold with a strain rate of 0.005 s(-1) has the benefit to generate mechanical stimuli based on both solid shear strain and fluid flow shear stress on large scaffold surface area. Values of perfusion inlet velocity or compression strain rate one order of magnitude lower may promote cell proliferation while values one order of magnitude higher may be detrimental for cells. FEM-CFD scaffold models may help to determine loading conditions promoting bone formation and to interpret experimental results from a mechanical point of view.

Simulation of bone tissue formation within a porous scaffold under dynamic compression

A computational model of mechanoregulation is proposed to predict bone tissue formation stimulated mechanically by overall dynamical compression within a porous polymeric scaffold rendered by micro-CT. Dynamic compressions of 0.5–5% at 0.0025–0.025 s−1 were simulated. A force-controlled dynamic compression was also performed by imposing a ramp of force from 1 to 70 N. The model predicts homogeneous mature bone tissue formation under strain levels of 0.5–1% at strain rates of 0.0025–0.005 s−1. Under higher levels of strain and strain rates, the scaffold shows heterogeneous mechanical behaviour which leads to the formation of a heterogeneous tissue with a mixture of mature bone and fibrous tissue. A fibrous tissue layer was also predicted under the force-controlled dynamic compression, although the same force magnitude was found promoting only mature bone during a strain-controlled compression. The model shows that the mechanical stimulation of bone tissue formation within a porous scaffold closely depends on the loading history and on the mechanical behaviour of the scaffold at local and global scales.

HOMOGENIZATION AND μCT ANALYSIS FOR THE TRABECULAR BONE REMODELLING

Fractures in trabecular bone are due to degradations: bone density decreases and microarchitecture is altered with respect to aging. Many authors aimed modelling degradation of trabecular bone architecture due to aging or disease ([Adachi, 2001], [Muller, 2005], [Liu, 2008]). The precited models were only based on biological kinetics and parameters: lengths of apposition and resorption phase, depth of resorption lacunae, frequency activation... However, models considered millions of elements and did not integrate mechanical stimulus as a precursor of bone remodelling adaptation. As a result, they have simulated the micro-structure degradation and not the influence of mechanical stimulus on bone stiffness.

Model of cancellous bone adaptation considering hypermineralised bone tissue

Ageing and a low physical activity often involve a decrease in bone mass and a mechanical weakening of bone at global scale, increasing fracture risk. In particular, cancellous bone tissue, which plays a mechanical role on the overall rigidity and strength of bone organs, is importantly degraded. Numerous computational models have been developed to simulate bone remodelling process and predict over decades the evolution of microstructure of cancellous bone and its mechanical behaviour (Van Der Linden et al. 2003; Liu et al. 2008). These models were based on mCT reconstruction of bone samples and consider generally the tissue as a homogeneous material. However, bone remodelling is spatially heterogeneous with concomitance of aged and new bone tissue. Moreover, mineralisation is a process occurring with time leading to heterogeneous mineral concentration and so mechanical properties. To determine the influence of a heterogeneous material on remodelling of cancellous bone, a computational study was performed here on a bone sample reconstructed in 3D from a mCT image stack. Heterogeneous material properties were defined depending on mineral density revealed by mCT grey value. The results show that hypermineralisation of cancellous bone influences considerably local mechanical behaviour although overall mechanical behaviour was not affected. Besides, bone cells are mechano-sensitive and adapt bone microstructure by resorbing aged or damaged tissue and apposing new one. So, an iterative computation of bone degradation was then performed in case of a low physical activity. Sites which were underloaded were considered as possible sites of remodelling process. This study shows that heterogeneous material properties may influence localisation of bone remodelling. This model which analyses alterations of cancellous bone microstructure may help in the prediction of fracture risk. It can also be implemented so as to predict effect of drug treatment on bone cell activity and the balance between apposition and resorption. 2. Methods