An Experimental and Computational Investigation of Bone Formation in Mechanically Loaded Trabecular Bone Explants

Abstract

Understanding how bone marrow multipotent stromal cells (MSCs) contribute to new bone formation and remodeling in vivo is of principal importance for informing the development of effective bone tissue engineering strategies in vitro. However, the precise in situ stimuli that MSCs experience have not been fully established. The shear stress generated within the bone marrow of physiologically loaded samples has never been determined, but could be playing an important role in the generation of sufficient stimulus for MSCs to undergo osteogenic differentiation. In this study fluid structure interaction (FSI) computational models were used in conjunction with a bioreactor which physiologically compresses explanted trabecular bone samples to determine whether MSCs can be directly stimulated by mechanical cues within the bone marrow. Experimentally loaded samples were found to have greater osteogenic activity, as verified by bone histomorphometry, compared to control static samples. FSI models demonstrated a linear relationship between increasing shear stress and decreasing bone volume. The FSI models demonstrated that bone strain, not marrow shear stress, was likely the overall driving mechanical signal for new bone formation during compression. However, the shear stress generated in the models is within the range of values which has been shown previously to generate an osteogenic response in MSCs.

Biomimetic fetal rotation bioreactor for engineering bone tissues—Effect of cyclic strains on upregulation of osteogenic gene expression

“…Bioreactor experiments have been conducted in the past to study the effects of combination systems that have both fluid flow and mechanical stimulation components to induce cellular proliferation and/or differentiation of 3D premature tissue grafts (Birmingham, Niebur, McNamara, & McHugh, ; Engelmayr et al, ; Haasper et al, ; Hoffmann, Feliciano, Martin, de Wild, & Wendt, ; Jagodzinski et al, ; S. T. Li et al, ; C. Liu et al, ; Orr & Burg, ; Witt, Duda, Bergmann, & Petersen, ). Few studies have compared the independent and combined effects of the perfusion flow and mechanical stimuli on cellular proliferation and osteogenic differentiation (Engelmayr et al, ; Jagodzinski et al, ; C. Liu et al, ).…”

Fatigue Prediction of Porous Magnesium Bone Scaffold Using Finite Element Method

“…The boundary condition of the FEA used in this simulation is shown in Figure 5. It defines the prescribed boundary condition of displacement on the top surface to simulate the uniaxial load because of the bone's mechanical loading [14]. Besides, a zero-displacement boundary condition is assigned to the opposite surface in its normal.…”

“…Nodes included in this boundary condition are confined only in the y-direction but can move freely inside the x-z plane. The model is fixed in the ydirection at the bottom, and a load-based strain 1000-3500 µε is applied to the upper surface according to the variation in the mechanical load of the bone [14] [15]. The magnesium's nonlinear-elastic/plastic material behaviour was modelled with: 3500 MPa as the elastic modulus, a Poisson's ratio of 0.35, and kinematic tangent modulus of 0.05 E.…”

Influence of bone marrow characteristic and trabecular bone morphology on bone remodelling process with FSI approach

“…To this date, experimental and simulation study have been performing in order to capture the value of these biomechanical stimuli that encourage the remodelling process. [6][7][8] Bone marrow is a prime component in trabecular bone, in which it accommodates bone predecessors' cells for bone remodelling. Thus, it is important to consider it presence to better represent the actual conditions of trabecular bone.…”