Search

This study aimed to investigate the hemodynamics of a novel fabric composite that can be used as a substitute for bovine pericardium. The structure is composed of ultrahigh molecular weight polyethylene (UHMWPE) fabric coated with thermoplastic polyurethane (TPU) membranes on both sides. In vitro experiments were carried out on two composite valve samples with different specifications and a bovine pericardial one with the same dimension and structure. Hemodynamic properties including the effective orifice area (EOA) and regurgitant fraction (RF) were obtained and compared through pulsatile-flow testing in a pulse duplicator. Using the particle image velocimetry (PIV) technique, frames of the downstream velocity field in the aortic valve chamber were captured during cardiac cycles. Then, the field of Reynolds shear stress (RSS), viscous shear stress (VSS), and turbulent kinetic energy (TKE) at peak systole were calculated. A fluid–structure interaction (FSI) model has also been used to verify the pulsatile-flow testing. Compared with the bovine pericardial valve, composite valves have no superiority regarding EOA and RF due to their slightly higher rigidity. However, shear stresses of composite valves were lower than those of the bovine pericardial valve indicating more stable blood flows, which means that composite leaflets have the potential to reduce the risks of thrombosis and hemolysis induced by the mechanical contact between the blood flow and leaflets of valve prostheses. [ABSTRACT FROM AUTHOR]

Abstract Thoracic endovascular aortic repair (TEVAR) has been introduced as a less invasive approach to the treatment of thoracic aortic aneurysm (TAA). However, the effectiveness of TEVAR in the treatment of TAA is often limited due to the complex anatomy of aortic arch. Flow preservation at the three supra-aortic branches further increases the overall technical difficulty. This study proposes a novel stent graft design with slit perforations that can positively alter the hemodynamics at the aortic arch while maintaining blood flow to supra-aortic branches. We carried out a computational fluid dynamic (CFD) analysis to evaluate flow characteristics near stented aortic arch in simplified TAA models, followed by in-vitro experiments using particle image velocimetry (PIV) in a mock circulatory loop. The hemodynamics result was studied in terms of time-averaged wall shear stress (TAWSS), oscillating shear index (OSI), and endothelial cell action potential (ECAP). The results showed that the stent graft with slit perforations can reduce the disturbed flow region considerably. Furthermore, the effect of the slits on flow preservation to the supra-aortic branches was simulated and compared with experimental results. The effectiveness of the stent graft with slit perforations in preserving flow to the branches was demonstrated by both simulated and experimental results. Low TAWSS and elevated ECAP were observed in the aortic arch aneurysm after the placement of the stent graft with slits, implying the potential of thrombus formation in the aneurysm. On the other hand, the effects of the stent grafts with full-slit design and half-slit design on the shear stress did not differ significantly. The present analysis indicated that not only could the stent graft with slit perforations shield the aneurysm from rupture, but also it resulted in a favorable environment for thrombus that can contribute to the shrinkage of the aneurysm. [ABSTRACT FROM AUTHOR]

Collective cell movement is critical in pathological processes such as wound healing and cancer invasion. It entails complex interactions between adjacent cells and between cells-extracellular matrices. Most studies measure the migration patterns and force propagation by placing cells on flat, patterned substrates. The cooperative behavior resulting from cell-cell interactions is not well understood. We have developed a multi-channel microfluidic device that has junctional protein E-cadherin coated onto the sidewalls of the channels that enables the cells’ lateral interactions with their neighbors to be studied. Our study reveals that epithelial cells rely on lateral E-cadherin-based adhesions to maintain the cohesion of the group. Cells move faster in narrower channels, but the average velocity along the channels is reduced in E-cadherin coated channels versus non-adhesive channels. We have directly measured the forces in the cross-linking protein, alpha-actinin, using FRET sensors during cell migration, and found that higher tension exists at the cell edges adjacent to the walls coated with E-cadherin, the implication being E-cadherin transmits the shear forces but does not provide a driving force for this migration. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLS) reside in the synovial membrane of diarthrodial joints and are exposed to a dynamic fluid environment that presents both physical and chemical stimuli. The ability of FLS to sense and respond to these stimuli plays a key role in their normal function, and is implicated in the alterations to function that occur in osteoarthritis (OA). The present work characterizes the response of FLS to fluid flow-induced shear stress via real-time calcium imaging, and tests the hypothesis that this response is modulated by interleukin-1α (IL-1α), a cytokine elevated in OA. FLS demonstrated a robust calcium signaling response to fluid shear that was dose dependent upon stress level and required both external and internal calcium sources. Preconditioning with 10 ng/mL IL-1α for 24 h heightened this shear stress response by significantly increasing the percent of responding cells and peak magnitude, while significantly decreasing the time for a peak to occur. Intercellular communication via gap junctions was found to account for a portion of the FLS population response in normal conditions, and was significantly increased by IL-1α preconditioning. IL-1α was also found to significantly increase average length and incidence of the primary cilium, an organelle commonly implicated in shear mechanosensing. These findings suggest that the elevated levels of IL-1α found in the OA environment heighten FLS sensitivity to fluid shear by altering both intercellular communication and individual cell sensitivity, which could affect downstream functions and contribute to progression of the disease state. [ABSTRACT FROM AUTHOR]

Blood vessels often experience torsion along their axes and it is essential to understand their biological responses and wall remodeling under torsion. To this end, a rat model was developed to investigate the arterial wall remodeling under sustained axial twisting in vivo . Rat carotid arteries were twisted at 180° along the longitudinal axis through a surgical procedure and maintained for different durations up to 4 weeks. The wall remodeling in these twisted arteries was examined using histology, immunohistochemistry and fluorescent microscopy. Our data showed that arteries remodeled under twisting in a time-dependent manner during the 4 weeks post-surgery. Cell proliferation, MMP-2 and MMP-9 expressions, medial wall thickness and lumen diameter increased while collagen to elastin ratio decreased. The size and number of internal elastic lamina fenestrae increased with elongated shapes, while the endothelial cells elongated and aligned towards the blood flow direction gradually. These results demonstrated that sustained axial twisting results in artery remodeling in vivo . The rat carotid artery twisting model is an effective in vivo model for studying arterial wall remodeling under long-term torsion. These results enrich our understanding of vascular biology and arterial wall remodeling under mechanical stresses. [ABSTRACT FROM AUTHOR]

Despite substantial evidence for the central role of hemodynamic shear stress in the functional integrity of vascular endothelial cells, hemodynamic and molecular regulation of the endocardial endothelium lining the heart chambers remains understudied. We propose that regional differences in intracardiac hemodynamics influence differential endocardial gene expression leading to phenotypic heterogeneity of this cell layer. Measurement of intracardiac hemodynamics was performed using 4-dimensional flow MRI in healthy humans ( n =8) and pigs ( n =5). Local wall shear stress (WSS) and oscillatory shear indices (OSI) were calculated in three distinct regions of the LV – base, mid-ventricle (midV), and apex. In both the humans and pigs, WSS values were significantly lower in the apex and midV relative to the base. Additionally, both the apex and midV had greater oscillatory shear indices (OSI) than the base. To investigate regional phenotype, endocardial endothelial cells (EEC) were isolated from an additional 8 pigs and RNA sequencing was performed. A false discovery rate of 0.10 identified 1051 differentially expressed genes between the base and apex, and 321 between base and midV. Pathway analyses revealed apical upregulation of genes associated with translation initiation. Furthermore, tissue factor pathway inhibitor (TFPI; mean 50-fold) and prostacyclin synthase (PTGIS; 5-fold), genes prominently associated with antithrombotic protection, were consistently upregulated in LV apex. These spatio-temporal WSS values in defined regions of the left ventricle link local hemodynamics to regional heterogeneity in endocardial gene expression. [ABSTRACT FROM AUTHOR]

In this review we focus on shear targeted drug delivery as a novel strategy to selectively deliver drugs to sites of vascular obstruction. We review the physics of stenotic (abnormally narrowed) blood vessels, while focusing mainly on the hemodynamics and transport phenomena at these sites. We then discuss how the local abnormal levels of shear stress, which can mechanically activate platelets, can be leveraged for localized drug delivery. We describe the development of Shear Activated Nano-particle Aggregates (SA-NPAs) that are designed to release and localize their nanoparticle drug carriers at sites of vascular stenosis. We present results in a variety of in vivo models, demonstrating the superiority of SA-NPAs carrying a thrombolytic drug compared to conventional treatment with the free drug. We also describe, shear-stress sensitive lenticular liposomes, which also show selective release under stenotic flow conditions. We then discuss limitations of both technologies, challenges in this new field and potential future applications. Altogether, we believe that mechano-sensitive therapeutics may offer a potential new approach for treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Shear stress is one of the main stress type produced by speech, mastication or tooth movement. The mechano-response of human periodontal ligament (PDL) cells by shear stress and the mechanism are largely unknown. In our study, we investigated the effects of fluid shear stress on proliferation, migration and osteogenic potential of human PDL cells. 6 dyn/cm 2 of fluid shear stress was produced in a parallel plate flow chamber. Our results demonstrated that fluid shear stress rearranged the orientation of human PDL cells. In addition, fluid shear stress inhibited human PDL cell proliferation and migration, but increased the osteogenic potential and expression of several growth factors and cytokines. Our study suggested that shear stress is involved in homeostasis regulation in human PDL cells. Inhibiting proliferation and migration potentially induce PDL cells to respond to mechanical stimuli in order to undergo osteogenic differentiation. [ABSTRACT FROM AUTHOR]

Although microfluidic systems have been important tools in analytical chemistry, life sciences, and medical research, their application was rather limited for drug-screening and biosensors. Here, we described a microfluidic device consisting of a multilayer micro-channel system that represented the hemodynamic cerebral vascular system. We analyzed wall shear stresses related to aneurysm formation in the circle of Willis (CoW) and their morphological variations using this system. This device was controlled by pneumatic valves, which occluded various major arteries by closing the associated channels. The hemodynamic analysis indicated that higher degrees of shear stress occurred in an anterior communicating artery (ACoA), particularly in the hypoplastic region of the posterior communicating artery (PCoA) and the P1 segment. Furthermore, occlusion of a common carotid artery (CCA) or a middle cerebral artery (MCA) increased the shear stress, whereas occlusion of a vertebral artery (VA) decreased the shear stress. These results indicate that the morphological variation of the CoW may affect aneurysm formation resulting from increased wall shear stress. Therefore, the technique described in this paper provides a novel method to investigate the hemodynamics of complex cerebral vascular systems not accessible from previous clinical studies. [ABSTRACT FROM AUTHOR]

Soft tissue injuries, such as anterior cruciate ligament rupture, ankle sprain and foot skin problems, frequently occur during cutting maneuvers. These injuries are often regarded as associated with abnormal joint torque and interfacial friction caused by excessive external and in-shoe shear forces. This study simultaneously investigated the dynamic in-shoe localized plantar pressure and shear stress during lateral shuffling and 45° sidestep cutting maneuvers. Tri-axial force transducers were affixed at the first and second metatarsal heads, lateral forefoot, and heel regions in the midsole of a basketball shoe. Seventeen basketball players executed both cutting maneuvers with maximum efforts. Lateral shuffling cutting had a larger mediolateral braking force than 45° sidestep cutting. This large braking force was concentrated at the first metatarsal head, as indicated by its maximum medial shear stress (312.2±157.0kPa). During propulsion phase, peak shear stress occurred at the second metatarsal head (271.3±124.3kPa). Compared with lateral shuffling cutting, 45° sidestep cutting produced larger peak propulsion shear stress (463.0±272.6kPa) but smaller peak braking shear stress (184.8±181.7kPa), of which both were found at the first metatarsal head. During both cutting maneuvers, maximum medial and posterior shear stress occurred at the first metatarsal head, whereas maximum pressure occurred at the second metatarsal head. The first and second metatarsal heads sustained relatively high pressure and shear stress and were expected to be susceptible to plantar tissue discomfort or injury. Due to different stress distribution, distinct pressure and shear cushioning mechanisms in basketball footwear might be considered over different foot regions. [ABSTRACT FROM AUTHOR]

Osteocytes, positioned within bone's porous structure, are subject to interstitial fluid flow upon whole bone loading. Such fluid flow is widely theorized to be a mechanical signal transduced by osteocytes, initiating a poorly understood cascade of signaling events mediating bone adaptation to mechanical load. The objective of this study was to examine the time course of flow-induced changes in osteocyte gene transcript and protein levels using high-throughput approaches. Osteocyte-like MLO-Y4 cells were subjected to 2 h of oscillating fluid flow (1 Pa peak shear stress) and analyzed following 0, 2, 8, and 24 h post-flow incubation. Transcriptomic microarray analysis, followed by gene ontology pathway analysis, demonstrated fluid flow regulation of genes consistent with both known and unknown metabolic and inflammatory responses in bone. Additionally, two of the more highly up-regulated gene products -chemokines Cxci1 and Cxcl2, supported by qPCR - have not previously been reported as responsive to fluid flow. Proteomic analysis demonstrated greatest up-regulation of the ATP-producing enzyme NDK, calcium-binding Calcyclin, and G protein-coupled receptor kinase 6. Finally, an integrative pathway analysis merging fold changes in transcript and protein levels predicted signaling nodes not directly detected at the sampled time points, including transcription factors c-Myc, c-Jun, and RelA/NF-KB. These results extend our knowledge of the osteocytic response to fluid flow, most notably up-regulation of Cxcl1 and Cxcl2 as possible paracrine agents for osteoblastic and osteoclastic recruitment. Moreover, these results demonstrate the utility of integrative, high-throughput approaches in place of a traditional candidate approach for identifying novel mechano-sensitive signaling molecules. [ABSTRACT FROM AUTHOR]

Background: Heterogeneity in plaque composition in human coronary artery bifurcations is associated with blood flow induced shear stress. Shear stress is generally determined by combing 3D lumen data and computational fluid dynamics (CFD). We investigated two new procedures to generate 3D lumen reconstructions of coronary artery bifurcations for shear stress computations. Methods: We imaged 10 patients with multislice computer tomography (MSCT) and intravascular ultrasound (IVUS). The 3D reconstruction of the main branch was based on the fusion of MSCT and IVUS. The proximal part of side branch was reconstructed using IVUS data or MSCT data, resulting in two different reconstructions of the bifurcation region. The distal part of the side branch was based on MSCT data alone. The reconstructed lumen was combined with CFD to determine the shear stress. Low and high shear stress regions were defined and shear stress patterns in the bifurcation regions were investigated. Results: The 3D coronary bifurcations were successfully generated with both reconstruction procedures. The geometrical features of the bifurcation region for the two reconstruction procedures did not reveal appreciable differences. The shear stress maps showed a qualitative agreement, and the low and high shear stress regions were similar in size and average shear stress values were identical. The low and high shear stress regions showed an overlap of approximately 75%. Conclusion: Reconstruction of the side branch with MSCT data alone is an adequate technique to study shear stress and wall thickness in the bifurcation region. The reconstruction procedure can be applied to further investigate the effect of shear stress on atherosclerosis in coronary bifurcations. [ABSTRACT FROM AUTHOR]

The role of low and oscillating shear stress as a key factor for localizing early atherosclerotic plaques is generally accepted. Once more advanced plaques protrude into the lumen, the shear stress they are exposed to changes. The influence of shear stress on plaque composition in advanced atherosclerosis is not fully understood. In this review, we discuss our recent studies on the relationship between shear stress and plaque composition and the location of plaque rupture in human coronary arteries. We have shown that elevated shear stress levels can be found over plaques inducing only mild luminal narrowing and are not subjected to treatment. Regional exposure of certain plaque regions to high shear stress is therefore a condition that will pertain for a prolonged period of time. We have also shown that in more advanced atherosclerosis the necrotic core experiences higher shear stress. Low shear stress plaque regions can be found downstream of the plaque and are stiffer. High shear stress plaque regions can be found either at the upstream, shoulder or cap region of the plaque and are softer. The plaque regions with the highest strain levels are the regions that are exposed to the highest shear stress. The high shear stress plaque regions are the only plaque regions that get softer over time. Finally, high shear stress is also associated with the location of plaque rupture in non-culprit lesion in human coronary arteries. Combining our findings with data from literature, we can conclude that advanced coronary plaques grow in the distal regions. The distal plaque regions are exposed to low shear stress, are stiffer and have a stable plaque phenotype. The regions exposed to high shear stress are softer, and are associated with vulnerable plaque features. [ABSTRACT FROM AUTHOR]

Abstract: Low-magnitude high-frequency (LMHF) loading has recently received attention for its anabolic effect on bone. The mechanism of transmission of the anabolic signal is not fully understood, but evidence indicates that it is not dependent on bone matrix strain. One possible source of signaling is mechanostimulation of the cells in the bone marrow. We hypothesized that the magnitude of the fluid shear stress in the marrow during LMHF loading is in the mechanostimulatory range. As such, the goal of this study was to determine the range of shear stress in the marrow during LMHF vibration. The shear stress was estimated from computational models, and its dependence on bone density, architecture, permeability, marrow viscosity, vibration amplitude and vibration frequency were examined. Three-dimensional finite element models of five trabecular bone samples from different anatomic sites were constructed, and a sinusoidal velocity profile was applied to the models. In human bone models during axial vibration at an amplitude of 1 g, more than 75% of the marrow experienced shear stress greater than 0.5Pa. In comparison, in vitro studies indicate that fluid induced shear stress in the range of 0.5 to 2.0Pa is anabolic to a variety of cells in the marrow. Shear stress at the bone-marrow interface was as high as 5.0Pa. Thus, osteoblasts and bone lining cells that are thought to reside on the endosteal surfaces may experience very high shear stress during LMHF loading. However, a more complete understanding of the location of the various cell populations in the marrow is needed to quantify the effects on specific cell types. This study suggests the shear stress within bone marrow in real trabecular architecture during LMHF vibration could provide the mechanical signal to marrow cells that leads to bone anabolism. [Copyright &y& Elsevier]

Abstract: In the present work, human breast cancer cells MCF-7 mixed with polyethylenimine: deoxyribonucleic acid complex and microbubbles were exposed to 1-MHz ultrasound at low acoustic driving pressures ranging from 0.05 to 0.3MPa. The sonoporation pores generated on the cell membrane were examined with scanning electron microscopy. The transfection efficiency and cell viability were evaluated with flow cytometry. The results showed that ultrasound sonication under the current exposure condition could generate cell pores with mean size ranging from about 100nm to 1.25μm, and that larger sonoporation pores would be generated with the increasing acoustic pressure or longer treatment time, leading to the enhancement of transfection efficiency and the reduction of cell viability. The simulations based on the Marmottant model were performed to test the hypothesis that the microstreaming-induced shear stress might be involved in the mechanisms of the low-intensity ultrasound induced sonoporation. The calculated shear stress resulting from the micro-streaming ranged from 15 to 680Pa corresponding to the applied acoustic pressures 0.05−0.3MPa, which is sufficient to induce reversible sonoporation. This study indicates that the shear stress related bio-effects may provide a base for strategies aimed at targeted drug delivery. [Copyright &y& Elsevier]

Abstract: Atherosclerotic plaques localize to regions of flow disturbance, i.e. bifurcations, branch points and regions of high curvature. Shear stress in these regions can be multi-directional due to complex flow patterns such as time-varying vortices. However, commonly used in vitro flow models are incapable of changing flow orientation to any direction other than the reverse. We have developed a novel in vitro flow system to enable changes in flow direction to any angle. When cells were pre-aligned in laminar shear, and then rotated 90°, cells re-aligned over 24h. Re-alignment involved actin remodeling by gradual rotation of actin stress fibers. This device will enable that analysis of how endothelial cells sense changes in flow direction as occur in vivo. [Copyright &y& Elsevier]

Abstract: Abnormal and excessive plantar pressure and shear are potential risk factors for high-heeled related foot problems, such as forefoot pain, hallux valgus deformity and calluses. Plantar shear stresses could be of particular importance with an inclined supporting surface of high-heeled shoe. This study aimed to investigate the contact pressures and shear stresses simultaneously between plantar foot and high-heeled shoe over five major weightbearing regions: hallux, heel, first, second and fourth metatarsal heads, using in-shoe triaxial force transducers. During both standing and walking, peak pressure and shear stress shifted from the lateral to the medial forefoot as the heel height increased from 30 to 70mm. Heel height elevation had a greater influence on peak shear than peak pressure. The increase in peak shear was up to 119% during walking, which was about five times that of peak pressure. With increasing heel height, peak posterolateral shear over the hallux at midstance increased, whereas peak pressure at push-off decreased. The increased posterolateral shear could be a contributing factor to hallux deformity. It was found that there were differences in the location and time of occurrence between in-shoe peak pressure and peak shear. In addition, there were significant differences in time of occurrence for the double-peak loading pattern between the resultant horizontal ground reaction force peaks and in-shoe localized peak shears. The abnormal and drastic increase of in-shoe shear stresses might be a critical risk factor for shoe-related foot disorders. In-shoe triaxial stresses should therefore be considered to help in designing proper footwear. [Copyright &y& Elsevier]

Abstract: Fluid flow in the bone lacuno–canalicular network can induce dynamic fluctuation of intracellular calcium concentration ([Ca2+]i) in osteoblasts, which plays an important role in bone remodeling. There has been limited progress in the mathematical modeling of this process probably due to its complexity, which is controlled by various factors such as Ca2+ channels and extracellular messengers. In this study we developed a mathematical model to describe [Ca2+]i response induced by fluid shear stress (SS) by integrating the major factors involved and analyzed the effects of different experimental setups (e.g. [Ca2+]i baseline, pretreatment with ATP). In this model we considered the ATP release process and the activities of multiple ion channels and purinergic receptors. The model was further verified quantitatively by comparing the simulation results with experimental data reported in literature. The results showed that: (i) extracellular ATP concentration has more significant effect on [Ca2+]i baseline (73% increase in [Ca2+]i with extracellular ATP concentration varying between 0 and 10μM), as compared to that induced by SS (25% variation in [Ca2+]i with SS varying from 0 to 3.5Pa); (ii) Pretreatment with ATP-medium results in different [Ca2+]i response as compared to the control group (ATP-free medium) under SS; (iii) Relative [Ca2+]i fluctuation over baseline is more reliable to show the [Ca2+]i response process than the absolute [Ca2+]i response peak. The developed model may improve the experimental design and facilitate our understanding of the mechanotransduction process in osteoblasts. [Copyright &y& Elsevier]

Abstract: The lymphatic system is an extensive vascular network featuring valves and contractile walls that pump interstitial fluid and plasma proteins back to the main circulation. Immune function also relies on the lymphatic system''s ability to transport white blood cells. Failure to drain and pump this excess fluid results in edema characterized by fluid retention and swelling of limbs. It is, therefore, important to understand the mechanisms of fluid transport and pumping of lymphatic vessels. Unfortunately, there are very few studies in this area, most of which assume Poiseuille flow conditions. In vivo observations reveal that these vessels contract strongly, with diameter changes of the order of magnitude of the diameter itself over a cycle that lasts typically 2–3s. The radial velocity of the contracting vessel is on the order of the axial fluid velocity, suggesting that modeling flow in these vessels with a Poiseuille model is inappropriate. In this paper, we describe a model of a radially expanding and contracting lymphatic vessel and investigate the validity of assuming Poiseuille flow to estimate wall shear stress, which is presumably important for lymphatic endothelial cell mechanotransduction. Three different wall motions, periodic sinusoidal, skewed sinusoidal and physiologic wall motions, were investigated with steady and unsteady parabolic inlet velocities. Despite high radial velocities resulting from the wall motion, wall shear stress values were within 4% of quasi-static Poiseuille values. Therefore, Poiseuille flow is valid for the estimation of wall shear stress for the majority of the lymphangion contractile cycle. [Copyright &y& Elsevier]

Abstract: Microbubble facilitated ultrasound (US) application can enhance intracellular delivery of drugs and genes in endothelial cells cultured in static condition by transiently disrupting the cell membrane, or sonoporation. However, endothelial cells in vivo that are constantly exposed to blood flow may exhibit different sonoporation characteristics. This study investigates the effects of shear stress cultivation on sonoporation of endothelial cells in terms of membrane disruption and changes in the intracellular calcium concentration ([Ca2+]i). Sonoporation experiments were conducted using murine brain microvascular endothelial (bEnd.3) cells and human umbilical vein endothelial cells (HUVECs) cultured under static or shear stress (5dyne/cm2 for 5 days) condition in a microchannel environment. The cells were exposed to a short US tone burst (1.25MHz, 8μs duration, 0.24MPa) in the presence of DefinityTM microbubbles to facilitate sonoporation. Membrane disruption was assessed by propidium iodide (PI) and changes in [Ca2+]i measured by fura-2AM. Results from this study show that shear stress cultivation significantly reduced the impact of ultrasound-driven microbubbles activities on endothelial cells. Cells cultured under shear stress condition exhibited much lower percentage with membrane disruption and changes in [Ca2+]i compared to statically cultured cells. The maximum increases of PI uptake and [Ca2+]i were also significantly lower in the shear stress cultured cells. In addition, the extent of [Ca2+]i waves in shear cultured HUVECs was reduced compared to the statically cultured cells. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have renewed interest in the effects of perivascular tethering on vascular mechanics, particularly growth and remodeling. We quantified effects of axial and circumferential tethering on rabbit pial arterioles from the ventral occipital lobe of the brain. The homeostatic axial pre-stretch, which is influenced by perivascular tethering, was measured in situ to be 1.24±0.04. Using a cannulated microvessel preparation, wall mechanics were then quantified in vitro for isolated arterioles at low (1.10) or normal (1.24) values of axial stretch and for tethered arterioles having perivascular support. Axial stretch did not significantly affect changes in circumferential stretch or stress upon pressurization, but circumferential tethering caused arteriolar geometry to change from a circular cross-section at normal pressure to an elliptical one at pressures above and below normal. Calculations suggested that the observed levels of ellipticity could cause a modest decrease in volumetric blood flow, but also a pronounced variation in shear stress around the circumference of the arteriole. An elliptical cross-section could thus increase vascular resistance or promote luminal remodeling at pressures different from normal. This characterization of effects of perivascular tethering on pial arterioles should prove useful in future studies of roles of perturbed cerebral blood flow on the propensity of the cerebral microcirculation to remodel. [Copyright &y& Elsevier]

Abstract: Plaque rupture is the leading cause of acute coronary syndromes and stroke. Plaque formation, otherwise known as stenosis, preferentially occurs in the regions of arterial bifurcation or curvatures. To date, real-time assessment of stenosis-induced flow reversal remains a clinical challenge. By interfacing microelectromechanical system (MEMS) thermal sensors with the high frequency pulsed wave (PW) Doppler ultrasound, we proposed to assess flow reversal in the presence of an eccentric stenosis. We developed a 3-D stenotic model (inner diameter of 6mm, an eccentric stenosis with a height of 2.75mm, and width of 21mm) simulating a superficial arterial vessel. We demonstrated that heat transfer from the sensing element (2×80μm2) to the flow field peaked as a function of flow rates at the throat of the stenosis along the center/midline of arterial model, and dropped downstream from the stenosis, where flow reversal was detected by the high frequency ultrasound device at 45MHz. Computational fluid dynamics (CFD) codes are in agreement with the ultrasound-acquired flow profiles upstream, downstream, and at the throat of the stenosis. Hence, we characterized regions of eccentric stenosis in terms of changes in heat transfer along the midline of vessel and identified points of flow reversal with high spatial and temporal resolution. [Copyright &y& Elsevier]

Abstract: Osteocytes compose 90–95% of all bone cells and are the mechanosensors of bone. In this study, the strain experienced by individual osteocytes resulting from an applied fluid flow shear stress was quantified and correlated to two biological responses measured in real-time within the same individual osteocytes: (1) the upregulation of intracellular calcium and (2) changes in intracellular nitric oxide. Osteocyte-like MLO-Y4 cells were loaded with Fluo-4 AM and DAR-4M and exposed to uniform laminar fluid flow shear stresses of 2, 8, or 16dyn/cm2. Intracellular calcium and nitric oxide changes were determined by measuring the difference in fluorescence intensity from the cell’s basal level prior to fluid flow and the level immediately following exposure. Individual cell strains were calculated using digital image correlation. MLO-Y4 cells showed a linear increase in cell strain, intracellular calcium concentration, and nitric oxide concentration with an increase in applied fluid flow rate. The increase in intracellular calcium was well correlated to the strain that each cell experienced. This study shows that osteocytes exposed to the same fluid flow experienced a range of individual strains and changes in intracellular calcium and nitric oxide concentrations, and the changes in intracellular calcium were correlated with cell strain. These results are among the first to establish a relationship between the strain experienced by osteocytes in response to fluid flow shear and a biological response at the single cell level. Mechanosensing and chemical signaling in osteocytes has been hypothesized to occur at the single cell level, making it imperative to understand the biological response of the individual cell. [Copyright &y& Elsevier]

Abstract: Endothelial cells (ECs), besides being a permeability barrier between the blood and vessel wall, perform many important functions, e.g., cell migration, remodeling, proliferation, and the production, secretion and metabolism of biochemical substances, as well as the regulation of contractility of vascular smooth muscle cells (SMCs). Their function is modulated by chemical ligands as well as mechanical factors. The mechanical stresses acting on the vessel wall include the normal and circumferential stresses that result from the action of blood pressure, the shear stress that acts parallel to the luminal surface of the vessel due to blood flow and the magnitude and orientation of the gravitation field. The aim of this work was to design and construct a novel bioreactor for the stimulation of endothelial cells in vitro with a combination of mechanical factors that simulates their in vivo environment. [Copyright &y& Elsevier]

Abstract: Bone responds to changes in its mechanical environment, but the mechanisms by which it does so are poorly understood. One hypothesis of mechanosensing in bone states that osteocytes can sense the flow of fluid through the canalicular system. To study this in vitro a number of fluid flow devices have been designed in which cells are placed between parallel plates in sealed chambers. Fluid flows through the chambers at controlled rates, most commonly driven by a peristaltic pump. In addition to fluid flow, high pressures have been observed in these chambers, but the effect of this on the cellular responses has generally been ignored or considered irrelevant, something challenged by recent cellular experiments using pressure only. We have, therefore, devised a system in which we can considerably reduce the pressure while maintaining the flow rate to enable study of their effects individually and in combination. As reducing pressure also reduces the risk of leaks in flow chambers, our system is suitable for real-time microscopical experiments. We present details of the new systems and of experiments with osteoblasts to illustrate the effects of fluid flow with and without additional pressure on the translocation of β-catenin to the nucleus. [Copyright &y& Elsevier]

Abstract: An analytical model of the fluid/cell mechanical interaction was developed. The interfacial shear stress, due to the coupling between the fluid and the cell deformation, was characterized by a new dimensionless number N fs . For N fs above a critical value, the fluid/cell interaction had a damping effect on the interfacial shear stress. Conversely, for N fs below this critical value, interfacial shear stress was amplified. As illustration, the role of the dynamic fluid/cell mechanical coupling was studied in a specific biological situation involving cells seeded in a bone scaffold. For the particular bone scaffold chosen, the dimensionless number N fs was higher than the critical value. In this case, the dynamic shear stress at the fluid/cell interface is damped for increasing excitation frequency. Interestingly, this damping effect is correlated to the pore diameter of the scaffold, furnishing thus target values in the design of the scaffold. Correspondingly, an efficient cell stimulation might be achieved with a scaffold of pore size larger than 300μm as no dynamic damping effect is likely to take place. The analytical model proposed in this study, while being a simplification of a fluid/cell mechanical interaction, brings complementary insights to numerical studies by analyzing the effect of different physical parameters. [Copyright &y& Elsevier]

Abstract: Red blood cell (RBC) aggregation is becoming an important hemorheological parameter, which exhibits a unique temperature dependence. However, further investigation is still required for understanding the temperature-dependent characteristics of hemorheology that includes RBC aggregation. In the present study, blood samples were examined at 3, 10, 20, 30, and 37°C. When the temperature decreases, the whole-blood and plasma viscosities increase, whereas the aggregation indices (AI, M, and b) yield contrary results. Since these contradictory results are known to arise from an increase in the plasma viscosity as the temperature decreases, aggregation indices that were corrected for plasma viscosity were examined. The corrected indices showed mixed results with the variation of the temperature. However, the threshold shear rate and the threshold shear stress increased as the temperature decreased, which is a trend that agrees with that of the blood viscosity. As the temperature decreases, RBC aggregates become more resistant to hydrodynamic dispersion and the corresponding threshold shear stress increases as does the blood viscosity. Therefore, the threshold shear stress may help to better clarify the mechanics of RBC aggregation under both physiological and pathological conditions. [Copyright &y& Elsevier]