Oscillatory Bone Fluid Flow and its Role in Initiating Remodeling in the Absence of Matrix Strain

Author(s):  
Yixian Qin ◽  
Anita Saldanha ◽  
Tamara Kaplan

Abstract Load-generated intracortical fluid flow is proposed to be an important mediator for regulating bone mass and morphology [1]. Although the mechanism of cellular response to induced flow parameters, i.e., fluid pressure, pressure gradient, velocity, and fluid shear stress, are not yet clear, interstitial fluid flow driven by loading may be necessary to explain the adaptive response of bone, which is either coupled with load-induced strain magnitude or independent with matrix strain per se [2]. It has been demonstrated that load-induced intracortical fluid flow is contributed by both bone matrix deformation and induced intramedullary (IM) pressure [3]. To examine the hypothesis of fluid flow generated adaptation, it is necessary to test the mechanism under the circumstances of solely fluid induced bone adaptation in the absence of matrix deformation. While our previous data has demonstrated that bone fluid flow and its associated streaming potential product can be influenced by the dynamic IM pressure quantitatively [4], the objective of this study was to evaluate fluid induced bone adaptation in an avian ulna model using oscillatory IM fluid pressure loading in the absence of bone matrix strain. The potential fluid pathway was measured in the model.

Author(s):  
W. Scott Van Dyke ◽  
Eric Nauman ◽  
Ozan Akkus

The causes, mechanisms, and biology of bone adaptation have been under intense investigation ever since Julius Wolff proposed that bone architecture is determined by mathematical laws as a result of mechanical loading. How bone responds to mechanical loads by converting the mechanical signals into chemical signals is known as mechanotransduction. The in vivo environment of bone is complex, and most studies of cell-level phenomena have relied on the use of in vitro experiments using mechanical bioreactors. The main types of bioreactors are fluid flow shear stress, tensile and/or compressive strain, and hydrostatic pressure [1–2]. Of these bioreactors, the most intuitive mechanical stimulus for bone would be the tensile and compressive strain bioreactors. However, many researchers now claim that shear stress via interstitial fluid flow in the lacunar-canalicular porosity is the primary mechanosensory stimulus [3]. A handful of studies have attempted to compare the effects of both of these mechanical stimuli on osteoblasts, but these studies are lacking in two respects [4–6]. First, if both fluid flow and strain are performed in the same bioreactor, the magnitude of one loading mode is explicitly determined through constitutive equations, while the other is only estimated. Second, if the magnitudes of the loading modes are able to be explicitly determined they are performed in different bioreactors, providing the cells different extracellular environments. Therefore, a highly controllable dual-loading mode mechanical bioreactor, as described and characterized in this study, is a necessary tool to further understand the mechanotransduction of bone.


Author(s):  
Yi-Xian Qin ◽  
Tamara Kaplan ◽  
Hoyan Lam

Anabolic response of bone to interstitial fluid flow is strongly dependent on the dynamic components of the fluid pressure, implying that fluid flow is a critical regulatory component to bone mass and morphology. While the fluid stimulus can be potentially applied for therapeutic in promoting turnover, the hypothesis of fluid induced bone adaptation was evaluated in an avian ulna model using varied flow rates and magnitudes. Total of 12 one-year old male avian animals was used in this study. A sinusoidal fluid pressure was applied to the experimental ulna 10 min/day for 4 weeks. Three experimental groups of loading were performed at 1 and 30 Hz of fluid loading. The results reveal an increase of 22.7%±7.2 in trabecular volume for group of 30 Hz, 76mmHg loading, while it had only 0.5 % increase at 1Hz, 76 mmHg loading. Under physiologic fluid pressure, a higher flow rate of stimuli generates much higher remodeling response than a lower rate of loading. This implies that bone turnover may be sensitive to the dynamic components of fluid flow, thereby initiating the adaptive response.


Materials ◽  
2004 ◽  
Author(s):  
Colby C. Swan ◽  
Hyung-Joo Kim

To explore the potential role that load-induced fluid flow plays as a mechano-transduction mechanism in bone adaptation, a lacunar-canalicular scale bone poroelasticity model is developed and exercised. The model uses micromechanics to homogenize the pericanalicular bone matrix, a system of straight circular cylinders in the bone matrix through which bone fluids can flow, as a locally anisotropic poroelastic medium. In this work, a simplified two-dimensional model of a periodic array of lacunae and their surrounding systems of canaliculi is developed and exercised to quantify local fluid flow characteristics in the vicinity of a single lacuna. When the cortical bone model is loaded, microscale stress and strain concentrations occur in the vicinity of individual lacunae and give rise to microscale spatial variations in the pore fluid pressure field. Consequently, loading of cortical bone can induce fluid flow in the canaliculi and exchange of fluid between canaliculi and lacunae. For realistic bone morphology parameters, and a range of loading frequencies, fluid pressures and fluid-solid shear stresses in the canalicular bone are computed and the associated energy dissipation in the models compared to that measured in physical in vitro experiments on human cortical bone. For realistic volume fractions of canaliculi, deformation-induced fluid flow is found to have a much larger characteristic time constant than deformation-induced flow in the Haversian system.


Author(s):  
HAO ZHANG ◽  
HAI-YING LIU ◽  
CHUN-QIU ZHANG ◽  
ZHEN-ZHONG LIU ◽  
WEI WANG

Background: Compact bone mainly consists of cylindrical osteon structures. In microgravity, the change in the mechanical microenvironment of osteocytes might be the root cause of astronauts’ bone loss during space flights. Methods: A multi-scale three-dimensional (3D) fluid–solid coupling finite element model of osteons with a two-stage pore structure was developed using COMSOL software based on the natural structure of osteocytes. Gradients in gravitational fields of [Formula: see text]1, 0, 1, 2.5, and 3.7[Formula: see text]g were used to investigate the changes in the mechanical microenvironment on osteocyte structure. The difference in arteriole pulsating pressure and static compression stress caused by each gravity gradient was investigated. Results: The mechanical response of osteocytes increased with the value of g, compared with the Earth’s gravitational field. For instance, the fluid pressure of osteocytes and the von Mises stress of bone matrix near lacunae decreased by 31.3% and 99.9%, respectively, in microgravity. Under static loading, only about 16.7% of osteocytes in microgravity and 58.3% of osteocytes in the Earth’s gravitational field could reach the fluid shear stress threshold of biological reactions in cell culture experiments. Compared with the Earth’s gravitational field, the pressure gradient inside osteocytes severely decreased in microgravity. Conclusion: The mechanical microenvironment of osteocytes in microgravity might cause significant changes in the mechanical microenvironment of osteocytes, which may lead to disuse osteoporosis in astronauts.


Author(s):  
Xuanhao Sun ◽  
Vipuil Kishore ◽  
Kateri Fites ◽  
Ozan Akkus

Bone cells are responsible for sensing and converting the mechanical signals into cellular signals to drive bone adaptation and damage repair [1]. Cell-mediated repair of bone is reported to be in preferential association with regions filled with microdamage [2]. Although different theories have been proposed for mechanisms involved in those processes (such as substrate deformation, fluid flow shear, and hydrostatic pressure in mechanotransduction [3], or microcrack and osteocyte apoptosis in damage detection [4]), knowledge on the exact form of physical stimuli which trigger bone cells, especially in critically loaded regions of bone, is still elusive.


Author(s):  
M. Hu ◽  
R. Yeh ◽  
M. Lien ◽  
Y. X. Qin

Osteoporosis is a debilitating disease characterized as decreased bone mass and structural deterioration of bone tissue. Osteoporotic bone tissue turns itself into altered structure, which leads to weaker bones that are more susceptible for fractures. While often happening in elderly, long-term bed-rest patients, e.g. spinal cord injury, and astronauts who participate in long-duration spaceflights, osteoporosis has been considered as a major public health thread and causes great medical cost impacts to the society. Mechanobiology and novel stimulation on regulating bone health have long been recognized. Loading induced bone fluid flow, as a critical mechanotransductive promoter, has been demonstrated to regulate cellular signaling, osteogenesis, and bone adaptation [4]. As one of the factors that mediate bone fluid flow, intromedullary pressure (ImP) creates a pressure gradient that further influence the magnitude of mechanotransductory signals [5]. As for a potential translational development of ImP, our group has recently introduced a novel, non-invasive dynamic hydraulic stimulation (DHS) on bone structural enhancement. Its promising effects on inhibition of disuse bone loss has been shown with 2 Hz loading through a 4-week hindlimb suspension rat study followed by microCT analysis. At the cellular level, mesenchymal stem cells (MSCs) are defined by their self-renewal ability and that to potentially differentiate into the cells that form tissues such as bone [1]. To further elucidate the cellular effects of DHS and its potential mechanism on bone quality enhancement, the objective of this study was to measure MSC quantification in response to the in vivo mechanical signals driven by DHS.


Author(s):  
M. Hu ◽  
J. Cheng ◽  
S. Ferreri ◽  
F. Serra-Hsu ◽  
W. Lin ◽  
...  

Bone loss is a critical health problem of astronauts in long-term space missions. A growing number of evidence has pointed out bone fluid flow as a critical regulator in mechanotransductive signaling and bone adaptation. Intramedullary pressure (ImP) is a key mediator for bone fluid flow initiation and it influences the osteogenic signals within the skeleton. The potential ImP-induced bone fluid flow then triggers bone adaptation [1]. Previous in vivo study has demonstrated that ImP induced by oscillatory electrical stimulations can effectively mitigate disuse osteopenia in a frequency-dependent manner in a disuse rat model [2, 3]. In order to develop the translational potentials of ImP, a non-invasive intervention with direct fluid flow coupling is necessary to develop new treatments for microgravity-induced osteopenia/osteoporosis.


1996 ◽  
Vol 271 (1) ◽  
pp. E205-E208 ◽  
Author(s):  
D. L. Johnson ◽  
T. N. McAllister ◽  
J. A. Frangos

Interstitial fluid flow may mediate skeletal remodeling in response to mechanical loading. Because nitric oxide (NO) has been shown to be an osteoblast mitogen and inhibitor of osteoclastic resorption, we investigated and characterized the role of fluid shear on the release of NO in osteoblasts. Rat calvarial cells in a stationary culture produced undetectable levels of NO. Fluid shear stress (6 dyn/cm2) rapidly increased NO release rate to 9.8 nmol.h-1.mg protein-1 and sustained this production for 12 h of exposure to flow. Cytokine treatment also induced NO synthesis after a 12-h lag phase of zero production, followed by a production rate of 0.6 nmol.h-1.mg protein-1. Flow-induced NO production was blocked by the NO synthase (NOS) inhibitor NG-amino-L-arginine, but not by dexamethasone, which suggests that the flow stimulated a constitutive NOS isoform. This is the first time that a functional constitutively present NOS isoform has been identified in osteoblasts. Moreover, fluid flow represents the most potent stimulus of NO release in osteoblasts reported to date. Fluid flow-induced NO production may therefore play a primary role in bone maintenance and remodeling.


2018 ◽  
Vol 18 (07) ◽  
pp. 1840007
Author(s):  
XIAO-GANG WU ◽  
TENG ZHAO ◽  
XIAO-HONG WU ◽  
JIANG-LAN XIE ◽  
KUI-JUN CHEN ◽  
...  

Physiological loads are non-axisymmetric and can lead to interstitial bone fluid flow, particularly in osteon. According to research, interstitial bone fluid flow plays a key role in bone mechanotransduction. To evaluate the poroelastic responses of a non-axisymmetric loaded osteon, this paper presents a finite element osteon model that is bulit by using the Comsol Multiphysics software. Obtained results show that under the same loading amplitude, the generated pressure and velocity amplitudes in the axial compression loading case are the largest, followed by that in the compressive bending loading, and smallest in the bending case. Moreover, the induced pressure and velocity amplitudes in axial compression loading exhibit an axial symmetrical distribution and axial centrosymmetric distribution in the compressive bending. In the bend loading case, the pressure amplitude presents an antisymmetric distribution, but the velocity amplitude is axially symmetrically distributed. Therefore, the distributions of pressure and velocity are definitely affected by load types, which lead to different bone fluid stimuli in mechanotransduction.


2000 ◽  
Vol 122 (4) ◽  
pp. 336-346 ◽  
Author(s):  
W. Michael Lai ◽  
Van C. Mow ◽  
Daniel D. Sun ◽  
Gerard A. Ateshian

The main objective of this study is to determine the nature of electric fields inside articular cartilage while accounting for the effects of both streaming potential and diffusion potential. Specifically, we solve two tissue mechano-electrochemical problems using the triphasic theories developed by Lai et al. (1991, ASME J. Biomech Eng., 113, pp. 245–258) and Gu et al. (1998, ASME J. Biomech. Eng., 120, pp. 169–180) (1) the steady one-dimensional permeation problem; and (2) the transient one-dimensional ramped-displacement, confined-compression, stress-relaxation problem (both in an open circuit condition) so as to be able to calculate the compressive strain, the electric potential, and the fixed charged density (FCD) inside cartilage. Our calculations show that in these two technically important problems, the diffusion potential effects compete against the flow-induced kinetic effects (streaming potential) for dominance of the electric potential inside the tissue. For softer tissues of similar FCD (i.e., lower aggregate modulus), the diffusion potential effects are enhanced when the tissue is being compressed (i.e., increasing its FCD in a nonuniform manner) either by direct compression or by drag-induced compaction; indeed, the diffusion potential effect may dominate over the streaming potential effect. The polarity of the electric potential field is in the same direction of interstitial fluid flow when streaming potential dominates, and in the opposite direction of fluid flow when diffusion potential dominates. For physiologically realistic articular cartilage material parameters, the polarity of electric potential across the tissue on the outside (surface to surface) may be opposite to the polarity across the tissue on the inside (surface to surface). Since the electromechanical signals that chodrocytes perceive in situ are the stresses, strains, pressures and the electric field generated inside the extracellular matrix when the tissue is deformed, the results from this study offer new challenges for the understanding of possible mechanisms that control chondrocyte biosyntheses. [S0148-0731(00)00604-X]


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