Mechanical Stimulation of Bone Marrow In Situ Induces Bone Formation in Trabecular Explants

Abstract

Low magnitude high frequency (LMHF) loading has been shown to have an anabolic effect on trabecular bone in vivo. However, the precise mechanical signal imposed on the bone marrow cells by LMHF loading, which induces a cellular response, remains unclear. This study investigates the influence of LMHF loading, applied using a custom designed bioreactor, on bone adaptation in an explanted trabecular bone model, which isolated the bone and marrow.Bone adaptation was investigated by performing micro CT scans pre and post experimental LMHF loading, using image registration techniques. Computational fluids dynamics models were generated using the pre-experiment scans to characterise the mechanical stimuli imposed by the loading regime prior to adaptation. Results here demonstrate a significant increase in bone formation in the LMHF loaded group compared to static controls and media flow groups.The calculated shear stress in the marrow was between 0.575 and 0.7 Pa, which is within the range of stimuli known to induce osteogenesis by bone marrow mesenchymal stem cells in vitro. Interestingly, a correlation was found between the bone formation balance (bone formation/resorption), trabecular number, trabecular spacing, mineral resorption rate, bone resorption rate and mean shear stresses. The results of this study suggest that the magnitude of the shear stresses generated due to LMHF loading in the explanted bone cores, has a contributory role in the formation of trabecular bone and improvement in bone architecture parameters.3

Comparison of titanium dioxide scaffold with commercial bone graft materials through micro-finite element modelling in flow perfusion

“…Our permeability values obtained computationally were comparable to cancellous bone as described by Grimm and Williams [15] and Nauman et al [35] and also similar to other studied bone graft materials using computational studies [3,10,36,45].…”

The In Situ Mechanics of Trabecular Bone Marrow: The Potential for Mechanobiological Response

“…The bone was assigned a uni form isotropic modulus of 15GPa and Poisson's ratio of 0.3, based on previous reports [38,39]. A no-slip interface was assumed at the bone-marrow interface, assuming that marrow cells adhere to the extracellular matrix [20,33], Sinusoidal strain profiles were applied along the inferio rsuperior axis of the trabecular bone models by fixing the inferior nodes and uniformly displacing the nodes on the superior surface. A no-slip interface was assumed at the bone-marrow interface, assuming that marrow cells adhere to the extracellular matrix [20,33], Sinusoidal strain profiles were applied along the inferio rsuperior axis of the trabecular bone models by fixing the inferior nodes and uniformly displacing the nodes on the superior surface.…”

“…Hydrostatic pressures of 10 MPa are chondrogenic in comparison to pressures of 0.1 MPa [23,24], and oscil latory pressures as small as 8kPa increase osteoblast formation in vitro [25,26] and bone formation in vivo [27], Hydrostatic pres sure also decreases osteoclastogenesis in vitro [28,29]. Indeed, isolated mechanical stimulation of marrow by compression [31,32] or by inertial load ing within trabecular bone explants [33] induces ossification and bone formation in the laboratory. Indeed, isolated mechanical stimulation of marrow by compression [31,32] or by inertial load ing within trabecular bone explants [33] induces ossification and bone formation in the laboratory.…”

Bone Homeostasis and Repair: Forced Into Shape

“…Using computational models, the resulting flow-induced shear stress in the canalicular space in bone has been estimated to be 0.5 to 2 Pa [34,36]. Similarly, estimated shear stress in the marrow near individual trabeculae is 0.5 to 2 Pa [33,37]. In some cases, shear stress may reach up to 5 Pa when the marrow is modeled as a highly viscous material [38].…”

“…During vigorous activity, strains can reach up to 10,000 με (1 %) [31]. Bone strain mediates fluid flow within the hard matrix, lacuna-canalicular space [32], and marrow [33], and is proposed to result in amplified strain at the level of the cell due to fluid drag through glycocalyx proteoglycans and integrin attachments located along the osteocyte processes [34,35]. Using computational models, the resulting flow-induced shear stress in the canalicular space in bone has been estimated to be 0.5 to 2 Pa [34,36].…”