Canalicular Fluid Flow Research Articles

Computer model of non-Newtonian canalicular fluid flow in lacunar-canalicular system of bone tissue.

Brittle bone diseases are a global healthcare problem for orthopaedic clinicians, that reduces bone strength and promotes bone fracture risk. In vivo studies reported that loading-induced fluid flow through the lacunar-canalicular channel (LCS) of bone tissue inhibit such bone loss and encourages osteogenesis i.e. new bone formation. Canalicular fluid flow converts mechanical signals into biological signals and regulates bone reconstruction by releasing signalling molecules responsible for mechanotransduction. In-silico model mostly considers canalicular fluid is Newtonian, however, physiological canalicular fluid may be non-Newtonian in nature as it contains nutrients and supplements. Accordingly, this study attempts to develop a two-dimensional in-silico model to compute loading-induced non-Newtonian canalicular fluid flow in a complex LCS of bone tissue. Moreover, canalicular fluid is considered as a Jeffery fluid, that can easily be reduced to Newtonian fluid as a special case. The results show that physiological loading modulates the canalicular fluid flow, wall shear stress (WSS) and streamline in bone LCS. Fluid velocity and WSS increases with increase in non-dimensional frequency and non-Newtonian parameter (Jeffery fluid parameters) and reduce with change in permeability. The outcomes of this study may provide new insights in the role of mechanical loading-induced non-Newtonian canalicular fluid flow dynamics in bone LCS. The key findings of this study can be used to improve the understanding of osteocyte mechanobiology involved inside the bone tissue.

A computational study on electric field-induced canalicular fluid flow in bone tissue

A computational study on electric field-induced canalicular fluid flow in bone tissue

Electromagnetic field induced alterations in fluid flow through lacuno-canalicular system of bone

Osteoporosis, bone-muscle disuse, and long-term exposure to space microgravity cause bone loss and promote bone fractures. Therapeutic devices and interventions for the prevention of bone loss and regulation of fracture healing are serious challenges for orthopaedic clinicians and researchers. Electromagnetic field exposure in combination with mechanical loading has the potential to prevent disuse bone loss as it promotes osteogenesis i.e., new bone formation. Loading-induced fluid motion in lacunar space acts as a stimulus for osteo-activities. Nevertheless, how the electromagnetic field regulates biomechanical stimulus such as fluid motion required for osteogenesis within bone tissue is not well understood. Accordingly, this paper attempts to establish a mathematical model to investigate the role of electromagnetic fields to alter the cantilever bending-induced lacunar fluid flow behaviour. A more realistic curvy canalicular channel subjected to electrohydrodynamics (EHD) mechanism is modelled to study poromechanical and canalicular fluid flow parameters such as pore-pressure gradient, fluid velocity, wall shear, and streamline patterns. Computational results indicate that electromagnetic fields modulate the fluid motion required for osteogenic activities even in bone tissues with higher porosity and permeability. The present study explains how electromagnetic fields possibly modulate mechanobiological stimulus in bone tissue. Based on the outcomes, an optimal loading regimen along with the electromagnetic field can be selected to enhance osteogenic response to prevent and mitigate irreversible bone loss that occurred due to microgravity and disuse.

Physiological Loading-Induced Interstitial Fluid Dynamics in Osteon of Osteogenesis Imperfecta Bone.

Osteogenesis imperfecta (OI), also known as "brittle bone disease," is a genetic bone disorder. OI bones experience frequent fractures. Surgical procedures are usually followed by clinicians in the management of OI. It has been observed physical activity is equally beneficial in reducing OI bone fractures in both children and adults as mechanical stimulation improves bone mass and strength. Loading-induced mechanical strain and interstitial fluid flow stimulate bone remodeling activities. Several studies have characterized strain environment in OI bones, whereas very few studies attempted to characterize the interstitial fluid flow. OI significantly affects bone micro-architecture. Thus, this study anticipates that canalicular fluid flow reduces in OI bone in comparison to the healthy bone in response to physiological loading due to altered poromechanical properties. This work attempts to understand the canalicular fluid distribution in single osteon models of OI and healthy bone. A poromechanical model of osteon is developed to compute pore-pressure and interstitial fluid flow as a function of gait loading pattern reported for OI and healthy subjects. Fluid distribution patterns are compared at different time-points of the stance phase of the gait cycle. It is observed that fluid flow significantly reduces in OI bone. Additionally, flow is more static than dynamic in OI osteon in comparison to healthy subjects. This work attempts to identify the plausible explanation behind the diminished mechanotransduction capability of OI bone. This work may further be extended for designing better biomechanical therapies to enhance the fluid flow in order to improve osteogenic activities in OI bone.

Canal of Hering loss is an initiating step for primary biliary cholangitis (PBC): A hypothesis

The origin and initiating features of PBC remain obscure despite decades of study. However, recent papers have demonstrated loss of canals of Hering (CoH) to be the earliest histologic change in liver biopsy specimens from patients with primary biliary cholangitis (PBC). We posit that CoH loss prior to significant inflammation or evidence of bile duct injury might be a very early, perhaps even an initiating lesion of PBC. As a potential target of inflammatory or toxic injury, CoH loss may initiate rather than follow the cascade of events leading to duct injury and loss and their sequelae. Toxins may be exogenous in origin, such as environmental toxins or drug exposures, or endogenous, resulting from genetic or epigenetic alterations in canalicular bile transporters upstream from the CoH. In turn, this hypothesis suggests that loss of CoH would lead to altered bile flow and composition injurious to downstream bile ducts, because bile composition has not been modulated by normal CoH physiologic functions or because, in the absence of CoH, canalicular fluid flow into the biliary tree is disrupted interfering with soluble trophic factors important for bile duct integrity. Regardless of the pathogenic mechanism causing CoH loss, only following such loss would the characteristic diagnostic findings of PBC become evident: damage to downstream interlobular and sub-lobular bile ducts. To the extent that the causal mechanisms for CoH loss can be identified, clinical identification (as through early identification of CoH loss) and intervention (depending on the inciting cause) may offer promise for treatment of this enigmatic disease.

Estimation of Loading-Driven Fluid-Flow Pattern in Lacunar-Canalicular Space Using Fluid Structure Interaction

Bone cells namely osteoblasts and osteocytes are assumed responsible for loading-induced osteogenesis. Osteocytes lie within the bone and connect to each other via cell process passing through canalicular spaces which forms a canalicular network. Fluid motion across this network acts as a medium of communication with neighbouring cells. Mechanical loading-induced pressure gradients in lacunar canalicular space (LCS) causes canalicular fluid to flow. However, it remains unclear how canalicular fluid motion and solid structure interact with each other under loading derived strain environment. In the present study, a two-way fluid structure interaction model is developed to estimate canalicular fluid flow behaviour. Flow streamlines and wall shear stress are computed. Results indicates that wall shear due to fluid flow on the pores wall is also in the same pattern as the velocity streams and velocity is maximum at those regions where the wall shear is also maximum. The outcomes provide a better understanding for developing strategies to enhance the fluid flow in bone, which may ultimately be useful in the development of effective countermeasure for the reversal of bone loss.

The role of fluid flow on bone mechanobiology: mathematical modeling and simulation

The effect of fluid flow on tissue adaptation was the focus of many research works during the last years. Moreover, the use of poroelasticity models to simulate and understand the interstitial flow movement has taken interest due to the possibility to include the fluid effect on mechanical simulations. In particular, shear stresses induced by bone canalicular fluid flow are suggested to be one of the mechanical stimulus controlling bone remodeling processes. Due to the high difficulty to measure canalicular fluid flow and shear stresses, computational poroelastic models can be used in order to estimate these parameters. In this work, a finite element dual porosity model based on Russian doll poroelasticity is developed. Two experiments with a turkey ulna and a human femur are simulated. Bone lacuno-canalicular fluid flow is computed and compared with the experimental results, focusing on the zones of bone remodeling and showing a relation between this flow and the bone formation process.

Canalicular Junctions in the Osteocyte Lacuno-Canalicular Network of Cortical Bone.

The osteocyte lacuno-canalicular network (LCN) is essential for bone remodeling because osteocytes regulate cell recruitment. This has been proposed to occur through liquid-flow-induced shear forces in the canaliculi. Models of the LCN have thus far assumed that it contains canaliculi connecting the osteocyte lacunae. However, here, we reveal that enlarged spaces occur at places where several canaliculi cross; we name these spaces canalicular junctions. We characterize them in detail within mice cortical bone using synchrotron nanotomography at two length scales, with 50 and 130 nm voxel size, and show that canalicular junctions occur at a density similar to that of osteocyte lacunae and that canalicular junctions tend to cluster. Through confocal laser scanning microscopy, we show that canalicular junctions are widespread as we have observed them in cortical bone from several species, even though the number density of the canalicular junctions was not universal. Fluid flow simulations of a simple model system with and without a canalicular junction clearly show that liquid mass transport and flow velocities are altered by the presence of canalicular junctions. We suggest that these canalicular junctions may play an important role in osteocyte communication and possibly also in canalicular fluid flow. Therefore, we believe that they constitute an important component in the bone osteocyte network.

Canalicular fluid flow induced by loading waveforms: A comparative analysis

Dynamic loading on the bone is beneficial in prevention and cure of bone loss as it encourages osteogenesis (i.e., new bone formation). Loading parameters such as strain magnitude, frequency, cycles, and strain rate (depending on loading waveform) affect the new bone formation. In-vivo studies suggested an optimal and osteogenic range of strain magnitude, frequency, and cycles to elicit the maximum new bone response. Still, there is no consensus on the selection of loading waveform. Animal studies on bone adaptation considered sinusoidal, and non-sinusoidal (e.g., trapezoidal, sawtooth, and triangular) loading waveforms according to physiological loadings (e.g., walking, running, and jumping etc.) without considering the relative effect of these waveforms on the loading-induced mechanical environment. The present study attempts to bridge this gap. Accordingly, this work hypothesizes that bone being a biphasic material (solid and fluid phases) experiences the same strain distribution for the different loading waves of the same amplitude, however, other components of the mechanical environment such as pore-pressure and interstitial fluid motion regulating the bone adaptation may differ. An in-vivo cantilever bending study is selected to substantiate the hypothesis. A poroelastic model is used to estimate the pore pressure and fluid motion developed in mouse tibia subjected to the: (i) trapezoidal, (ii) sawtooth, and (iii) triangular bending waves. Furthermore, poroelastic response of pore-pressure and fluid motion induced by these loading waveforms are compared and analyzed. This work also investigates how bone loss associated alterations in the microstructural environment of cortical bone affect the canalicular fluid motion induced by these waveforms. Overall results may be useful in designing optimal biomechanical interventions such as physical exercises to improve the bone health.

Mathematically modeling fluid flow and fluid shear stress in the canaliculi of a loaded osteon.

BackgroundMechanical load-induced intraosseous pressure gradients may result in some fluid stimuli effects, such as fluid flow and fluid shear stress (FSS), which may enable bone cells to detect external mechanical signals. Interstitial bone fluid flow is known to occur in lacunar–canalicular porosity (PLC).MethodsIn order to characterize lacunar–canalicular fluid flow behavior, a hierarchical osteon system is developed. The osteon is modeled as a poroelastic annular cylinder with two types of impermeable boundary cases considered on its outer wall: one is elastic restrained (Case I), whereas the other is displacement confined (Case II). Analytical solutions such as canalicular fluid velocity, pressure, fluid flow rate (FFR), and shear stress are obtained.ResultsResults show that the amplitudes of FFR and FSS are proportional to strain amplitude and frequency. However, the key loading factor governing canalicular fluid flow behavior is the strain rate. The larger canalicular radius is, the larger amplitudes of FFR and FSS generalized, especially, the FSS amplitude is proportional to canalicular radius. In addition, both FFR and FSS amplitudes produced in case II are larger than those of case I.ConclusionStrain rate can be acted as a representative loading parameter governing the canalicular fluid flow behavior under a physiological state. This model can facilitate better understanding the load induced the fluid permeation in the PLC. The approach can also be used to analyze the structure of the proteoglycan matrix in the fluid space surrounding the osteocytic process in the canaliculus.

Computer modelling of bone's adaptation: the role of normal strain, shear strain and fluid flow.

Bone loss is a serious health problem. In vivo studies have found that mechanical stimulation may inhibit bone loss as elevated strain in bone induces osteogenesis, i.e. new bone formation. However, the exact relationship between mechanical environment and osteogenesis is less clear. Normal strain is considered as a prime stimulus of osteogenic activity; however, there are some instances in the literature where osteogenesis is observed in the vicinity of minimal normal strain, specifically near the neutral axis of bending in long bones. It suggests that osteogenesis may also be induced by other or secondary components of mechanical environment such as shear strain or canalicular fluid flow. As it is evident from the literature, shear strain and fluid flow can be potent stimuli of osteogenesis. This study presents a computational model to investigate the roles of these stimuli in bone adaptation. The model assumes that bone formation rate is roughly proportional to the normal, shear and fluid shear strain energy density above their osteogenic thresholds. In vivo osteogenesis due to cyclic cantilever bending of a murine tibia has been simulated. The model predicts results close to experimental findings when normal strain, and shear strain or fluid shear were combined. This study also gives a new perspective on the relation between osteogenic potential of micro-level fluid shear and that of macro-level bending shear. Attempts to establish such relations among the components of mechanical environment and corresponding osteogenesis may ultimately aid in the development of effective approaches to mitigating bone loss.

Hierarchical model for strain generalized streaming potential induced by the canalicular fluid flow of an osteon

A hierarchical model is developed to predict the streaming potential (SP) in the canaliculi of a loaded osteon. Canaliculi are assumed to run straight across the osteon annular cylinder wall, while disregarding the effect of lacuna. SP is generalized by the canalicular fluid flow. Analytical solutions are obtained for the canalicular fluid velocity, pressure, and SP. Results demonstrate that SP amplitude (SPA) is proportional to the pressure difference, strain amplitude, frequency, and strain rate amplitude. However, the key loading factor governing SP is the strain rate, which is a representative loading parameter under the specific physiological state. Moreover, SPA is independent of canalicular length. This model links external loads to the canalicular fluid pressure, velocity, and SP, which can facilitate further understanding of the mechanotransduction and electromechanotransduction mechanisms of bones.

Interstitial fluid flow within bone canaliculi and electro-chemo-mechanical features of the canalicular milieu

Canalicular fluid flow is acknowledged to play a major role in bone functioning, allowing bone cells' metabolism and activity and providing an efficient way for cell-to-cell communication. Bone canaliculi are small canals running through the bone solid matrix, hosting osteocyte's dendrites, and saturated by an interstitial fluid rich in ions. Because of the small size of these canals (few hundred nanometers in diameter), fluid flow is coupled with electrochemical phenomena. In our previous works, we developed a multi-scale model accounting for coupled hydraulic and chemical transport in the canalicular network. Unfortunately, most of the physical and geometrical information required by the model is hardly accessible by nowadays experimental techniques. The goal of this study was to numerically assess the influence of the physical and material parameters involved in the canalicular fluid flow. The focus was set on the electro-chemo-mechanical features of the canalicular milieu, hopefully covering any in vivo scenario. Two main results were obtained. First, the most relevant parameters affecting the canalicular fluid flow were identified and their effects quantified. Second, these findings were given a larger scope to cover also scenarios not considered in this study. Therefore, this study gives insight into the potential interactions between electrochemistry and mechanics in bone and provides the rational for further theoretical and experimental investigations.

Decrease in the osteocyte lacunar density accompanied by hypermineralized lacunar occlusion reveals failure and delay of remodeling in aged human bone

Aging decreases the human femur's fatigue resistance, impact energy absorption, and the ability to withstand load. Changes in the osteocyte distribution and in their elemental composition might be involved in age-related bone impairment. To address this question, we carried out a histomorphometric assessment of the osteocyte lacunar distribution in the periosteal and endosteal human femoral cortexes of 16 female and 16 male donors with regard to age- and sex-related bone remodeling. Measurements of the bone mineral density distribution by quantitative backscattered electron imaging and energy dispersive X-ray analysis were taken to evaluate the osteocyte lacunar mineral composition and characteristics. Age-dependent decreases in the total osteocyte lacunar number were measured in all of the cases. This change signifies a risk for the bone's safety. Cortical subdivision into periosteal and endosteal regions of interest emphasized that, in both sexes, primarily the endosteal cortex is affected by age-dependent reduction in number of osteocyte lacunae, whereas the periosteal compartment showed a less pronounced osteocyte lacunar deficiency. In aged bone, osteocyte lacunae showed an increased amount of hypermineralized calcium phosphate occlusions in comparison with younger cases. With respect to Frost's early delineation of micropetrosis, our microanalyses revealed that the osteocyte lacunae are subject to hypermineralization. Intralacunar hypermineralization accompanied by a decrease in total osteocyte lacunar density may contribute to failure or delayed bone repair in aging bone. A decreased osteocyte lacunar density may cause deteriorations in the canalicular fluid flow and reduce the detection of microdamage, which counteracts the bone's structural integrity, while hypermineralized osteocyte lacunae may increase bone brittleness and render the bone fragile.

Targeted bone remodeling involves BMU steering as well as activation

Microdamage removal is an important function of bone remodeling. Experiments have repeatedly shown that remodeling of cortical bone by Basic Multicellular Units (BMUs) is initiated in response to microdamage, and this has become known as “targeted remodeling”. This paper considers the possibility that microdamage is not only able to activate new BMUs, but may also attract or “steer” existing BMUs as they continue to tunnel through the bone matrix. An initial analysis of the relationship of between mean microcrack length and BMU resorption space density in cortical bone indicates that BMUs have an effective area about 40 times greater than their actual cross-section. Interpreting this as evidence that the osteoclasts in a tunneling BMU are able to sense and steer toward microdamage, a model is developed for “BMU steering” based on the hypothesis that osteoclasts are guided not only in the principal stress direction, as proposed by Burger et al. (Burger, E.H., Klein-Nulend, J., Smit, T.H. Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon–a proposal. J. Biomech 36 (2003) 1453–1459), but also toward microdamage, depending on its proximity.

Reduced Iliac Cancellous Osteocyte Density in Patients With Osteoporotic Vertebral Fracture

Iliac cancellous osteocyte density declines with age, but its relationship to vertebral fracture pathogenesis is unknown. We performed iliac bone biopsy in 44 women with clinical vertebral fracture and 56 healthy women. The fracture patients had 34% fewer osteocytes but no reduction in percent occupied lacunae. Some patients destined to sustain vertebral fracture make cancellous bone with fewer osteocytes. Patient's with vertebral fracture have less bone than appropriate healthy controls, but other factors may contribute to bone fragility. Iliac cancellous osteocyte density declines with age in healthy women; we asked whether this variable differed between fracture patients and healthy controls. Two groups of women were assembled. Forty-four (mean age, 66.2 years) had unequivocal evidence of bone fragility manifested as painful nontraumatic vertebral fracture, and 56 (mean age, 62.2 years) were skeletally healthy. All subjects underwent iliac bone biopsy. From archival embedded biopsy cores, new sections were stained with Goldner's trichrome, in which we enumerated osteocyte-occupied lacunae (stained), empty lacunae (unstained), and total lacunae per bone area. Cancellous osteocyte density was 34% lower in the fracture group than in the controls (p < 0.001); this difference was not a consequence of higher turnover, having less bone, or the small difference in age. The area under the receiver operating characteristic (ROC) curve for discrimination between the groups was >90% for osteocyte density and <75% for bone volume/tissue volume (BV/TV). The disease-related osteocyte deficit was accompanied by a proportionate reduction in empty lacunae and no change in percent occupied lacunae; therefore, it was not the result of premature death. Both superficial bone (<25 microm from the surface) and deep bone (>45 microm from the surface) were affected. In contrast, the age-related deficit is accompanied by an increase in empty lacunae and fall in percent osteocyte-occupied lacunae and occurs only in deep bone, but not in superficial bone. In some patients destined to sustain spontaneous vertebral compression fracture, iliac cancellous bone is made with fewer osteocytes than normal; the mechanism of osteocyte incorporation into bone needs more detailed study. Osteocyte deficiency could contribute to bone fragility, either by impairing the detection of fatigue microdamage or by reducing canalicular fluid flow. Current practices of defining vertebral fracture based on morphometry alone regardless of symptoms, and diagnosing osteoporosis based on bone densitometry alone regardless of fracture history, should be reexamined.

Strain-derived canalicular fluid flow regulates osteoclast activity in a remodelling osteon—a proposal

The concept of bone remodelling by basic multicellular units is well established, but how the resorbing osteoclasts find their way through the pre-existing bone matrix remains unexplained. The alignment of secondary osteons along the dominant loading direction suggests that remodelling is guided by mechanical strain. This means that adaptation (Wolff's Law) takes place throughout life at each remodelling cycle. We propose that alignment during remodelling occurs as a result of different canalicular flow patterns around cutting cone and reversal zone during loading. Low canalicular flow around the tip of the cutting cone is proposed to reduce NO production by local osteocytes thereby causing their apoptosis. In turn, osteocyte apoptosis could be the mechanism that attracts osteoclasts, leading to further excavation of bone in the direction of loading. At the transition between cutting cone and reversal zone, however, enhanced canalicular flow will stimulate osteocytes to increase NO production, which induces osteoclast retraction and detachment from the bone surface. Together, this leads to a treadmill of attaching and detaching osteoclasts in the tip and the periphery of the cutting cone, respectively, and the digging of a tunnel in the direction of loading.

Canalicular fluid flow induced by bending of a long bone

Interstitial fluid flow has been hypothesized to underly mechanotransduction within bone. Here, we present an analytical model of fluid flows induced at the level of osteocyte canaliculi when a long bone is subject to functionally relevant bending loads. Dynamic bending of cortical bone results in a non-uniform longitudinal normal strain environment in which strain magnitude varies both temporally (i.e., at a given location, strain varies as a function of time) and spatio-temporally (i.e., at each given point in time, strain varies between locations). To account for the complexity posed by these two aspects of the strain environment, canalicular fluid flows were decomposed into temporal and spatio-temporal components. In terms of distribution around the cortex, temporal and spatio-temporal flows in the radial direction were both maximal near sites of peak strain magnitude. Spatio-temporal flows in the circumferential direction, in contrast, were maximal near locations of minimal strain magnitude (i.e. near the neutral axis). All fluid flow components were maximal during the first load cycle and reached markedly reduced steady state levels during subsequent load cycles. The novelty of the described model is that it provides the first estimate of canalicular fluid flows induced within a complexly loaded long bone. As the model may be readily extended to provide a simplistic accounting of the fluid flow profiles induced during functional loading and other exogenous loading regimes, the approach will enhance the ability to examine fluid flow related mechanotransduction within bone.