Characterization of hyaluronic acid and synovial fluid in stagnation point elongational flow

Hyaluronic acid (HA) is an important biomacromolecule, which fulfils a number of vital physiological functions (especially in the joint synovial fluid) and also has consumer and pharmaceutical applications. HA solution properties have already been quite thoroughly characterized in response to steady shear flows but are less well understood in highly deforming extensional flows. In this study, flow‐induced birefringence measurements are made as a function of the strain rate in planar elongational flow at the stagnation point of a cross‐slot device using HA solutions of a range of molecular weights and at dilute concentrations. The results provide macromolecular relaxation times, molecular weight distributions and the extensional viscosities and Trouton ratios of the fluids. The HA relaxation time is found to vary as ^1.8, which is consistent with a partially solvated, expanded coil. An intrinsic Trouton ratio is defined, which varies as ². The measurement of birefringence with strain rate is shown to be highly sensitive to the molecular weight distribution and can resolve subtle changes due to macromolecular degradation and the presence of fracture products. Mechanical degradation experiments in the cross‐slots indicate midchain scission of HA macromolecules, strongly suggesting near full extension of the high‐molecular weight fraction in the stagnation point extensional flow field. Taken together the results suggest a possible method for analysis of the HA in synovial fluid, and this concept is tested using synovial fluid obtained from porcine tarsal joint. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 287–305, 2014.     

Degeneration of normal articular cartilage induced by late phase osteoarthritic synovial fluid in beagle dogs

Objective

To investigate the pathogenesis of late phase osteoarthritic (OA) synovial fluid (SF) on normal articular cartilage in vivo and provide an understanding of degenerative cartilage extending in OA joint.

Methods

A random knee, each of 8 beagle dogs, received anterior cruciate ligament transection (ACLT) and was confirmed to have late phase OA degenerative changes at 24 weeks after operation. Thereafter, one random elbow of each canine was injected with autologous late phase OA knee SF. The contralateral elbow was injected with normal saline (NS) of the same volume as SF aspirated from ACLT knee. These two groups of elbows were labeled “SF” and “NS”. 8 other beagle dogs were left intact and placed in Group Control. After aseptic arthrocentesis was performed weekly on both elbows for 24 weeks, morphological changes were observed in the cartilage of the elbows, and expressions of 7 biological etiological factors of chondrocytes of the elbows were determined in Group SF, Group NS and Group Control, respectively.

Results

Morphological changes were observed in articular cartilage of the elbows in Group SF. Levels of unit area of collagen type I in the noncalcified, calcified and full zones of articular cartilage of the elbows in Group SF increased significantly. Level of unit area of collagen type III in the calcified zone of articular cartilage of the elbows in Group SF remained unchanged. Meanwhile, expressions of MMP-1 and MMP-3 of chondrocytes of the elbows in Group SF increased significantly. There was almost no difference between articular cartilage in Group NS and Group Control.

Conclusion

Based on these results, we conclude that OA degeneration of normal articular cartilage can be independently induced by late phase OA SF. Endogenous OA biological etiological factor may be one of the reasons causing degenerative cartilage extending in OA joint.     

Small animal models to understand pathogenesis of osteoarthritis and use of stem cell in cartilage regeneration

Osteoarthritis (OA) is one of the most common diseases, which affect the correct functionality of synovial joints and is characterized by articular cartilage degradation. Limitation in the treatment of OA is mostly due to the very limited regenerative characteristic of articular cartilage once is damaged. Small animal models are of particular importance for mechanistic analysis to understand the processes that affect cartilage degradation. Combination of joint injury techniques with the use of stem cells has been shown to be an important tool for understanding the processes of cartilage degradation and regeneration. Implementation of stem cells and small animal models are important tools to help researchers to find a solution that could ameliorate and prevent the symptoms of OA.     

The effects of slip velocity at a membrane surface on blood flow in the microcirculation

Closed-form solutions are presented for blood flow in the microcirculation by taking into account the influence of slip velocity at the membrane surface. In this study, the convective inertia force is neglected in comparison with that of blood viscosity on the basis of the smallness of the Reynolds number of the flow in microcirculation. The permeability property of the blood vessel is based on the well known Starling's hypothesis [11]. The effects of slip coefficient on the velocity and pressure fields are clearly depicted.     

CFD simulation of non-Newtonian fluid flow in anaerobic digesters

A general mathematical model that predicts the flow fields in a mixed-flow anaerobic digester was developed. In this model, the liquid manure was assumed to be a non-Newtonian fluid, and the flow governed by the continuity, momentum, and k-epsilon standard turbulence equations, and non-Newtonian power law model. The commercial computational fluid dynamics (CFD) software, Fluent, was applied to simulate the flow fields of lab-scale, scale-up, and pilot-scale anaerobic digesters. The simulation results were validated against the experimental data from literature. The flow patterns were qualitatively compared for Newtonian and non-Newtonian fluids flow in a lab-scale digester. Numerical simulations were performed to predict the flow fields in scale-up and pilot-scale anaerobic digesters with different water pump power inputs and different total solid concentration (TS) in the liquid manure. The optimal power inputs were determined for the pilot-scale anaerobic digester. Some measures for reducing dead and low velocity zones were proposed based upon the CFD simulation results.     

Effects of synovial fluid on the respiratory burst of granulocytes in rheumatoid arthritis

Neutrophil infiltration in the synovia is an important feature of the local inflammatory process associated with rheumatoid arthritis. The present study is focused on the effects exerted in vitro by the synovial fluid versus serum on the respiratory burst of granulocytes isolated either from blood or synovial fluid of rheumatoid arthritis patients. The respiratory burst was evaluated as superoxide anion release, by lucigenin-amplified chemiluminescence. Our data show that the respiratory burst of granulocytes isolated from rheumatoid arthritis patients might trigger a significant oxidative stress both in periphery and the inflamed joint. These cells show no pathological pattern when activated in vitro by the chemotactic peptide fMLP, heterologous synovial fluid or serum. Acellular synovial fluid amplifies the superoxide anion release induced by fMLP more than the corresponding serum, indicating that a bacterian infection in the joint might enhance the oxidative damage in the inflamed synovium.     

Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis

Context: Chemerin has been implicated to be correlated with inflammation.

Objective: This study aims to determine the association of chemerin levels in serum and synovial fluid (SF) with the disease severity of patients with knee Osteoarthritis (OA).

Methods: 124 patients with knee OA and 76 healthy controls were enrolled in this study.

Results: Chemerin levels in serum were significant higher with regard to paired SF. Chemerin levles in SF of knee OA patients were correlated with disease severity evaluated by KL grading criteria.

Conclusion: Chemerin levels may be involved in the pathophysiology of the development and progression of OA.     

The influence of artery wall curvature on the anatomical assessment of stenosis severity derived from fractional flow reserve: a computational fluid dynamics study

This study aims to investigate the influence of artery wall curvature on the anatomical assessment of stenosis severity and to identify a region of misinterpretation in the assessment of per cent area stenosis (AS) for functionally significant stenosis using fractional flow reserve (FFR) as standard. Five artery models of different per cent AS severity (70, 75, 80, 85 and 90%) were considered. For each per cent AS severity, the angle of curvature of the arterial wall varied from straight to an increasingly curved model (0°, 30°, 60°, 90° and 120°). Computational fluid dynamics was performed under transient physiologic hyperemic flow conditions to investigate the influence of artery wall curvature on the pressure drop and the FFR. The findings in this study may be useful in in vitro anatomical assessment of functionally significant stenosis. The FFR decreased with increasing stenosis severity for a given curvature of the artery wall. Moreover, a significant decrease in FFR was found between straight and curved models discussed for a given severity condition. These findings indicate that the curvature effect was included in the FFR assessment in contrast to minimum lumen area (MLA) or per cent AS assessment. The MLA or per cent AS assessment may lead to underestimation of stenosis severity. From this numerical study, an uncertainty region could be evaluated using the clinical FFR cutoff value of 0.8. This value was observed at 81.98 and 79.10% AS for arteries with curvature angles of 0° and 120° respectively. In conclusion, the curvature of the artery should not be neglected in in vitro anatomical assessment.     

Bone tissue engineering: the role of interstitial fluid flow

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.     

Ultrastructural evidence for paracellular fluid flow in the Malpighian tubules of a larval mayfly

The ultrastructure of the Malpighian tubules of larvae of the Mayfly Ecdyonurus dispar (Ephemeroptera) is described. There are about 60 tubules, which consist of four distinct regions. The most proximal section (region I) appears to be responsible for fluid secretion. A unique feature is the presence of channels leading off the main lumen, which end close to the basal border of the cells. Microvilli are confined to these channels in region I. Region II is a short spiral region, the cells of which possess long basal folds and associated mitochondria. Region III is a simple conducting tube leading to one of six collecting ducts (region IV) arranged radially around the gut. In each collecting duct there are two cell types present. Type 2 cells are relatively simple, but give rise to numerous, long, microvilli-like projections. Type 1 cells possess long basal folds, and curious membrane whorls in the apical zone. Evidence is presented which suggest that water movements into region I takes place via the paracellular route. Region II is probably a reabsorptive region, but the function of region IV, based on ultrastructural evidence is more difficult to elucidate.     

DPD simulation of non-Newtonian electroosmotic fluid flow in nanochannel

We use the dissipative particle dynamics (DPD) method to simulate the non-Newtonian electroosmotic flow (EOF) through nanochannels. Contrary to a large amount of past computational efforts dedicated to the study of EOF profile, this work pays attention to the EOF of non-Newtonian fluids, which has been rarely touched in past publications. Practically, there are many MEMS/NEMS devices, in which the EOF behaviour should be treated assuming both non-continuum and non-Newtonian conditions. Therefore, our concern in this work is to simulate the EOF through nanochannels considering both non-Newtonian fluid properties and non-continuum flow conditions. We have chosen DPD as our working tool because it provides several important advantages comparing with the classical time consuming molecular dynamics method. Using the DPD method, we explore the effect of a few important fluid properties and nanochannel parameters on the EOF behaviour and the resulting flow rate magnitudes. Our investigation will result in a number of findings, which have not been reported in past research works.     

The effects of variation in the arterial pulse waveform on perivascular flow

Cerebrospinal fluid (CSF) enters nervous tissues through perivascular spaces. Flow through these pathways is important for solute transport and to prevent fluid accumulation. Syringomyelia is commonly associated with subarachnoid space obstructions such as Chiari I malformation. However, the mechanism of development of these fluid-filled cavities is unclear. Studies have suggested that changes in the arterial and CSF pressures could alter normal perivascular flow. This study uses an idealised model of the perivascular space to investigate how variation in the arterial pulse influences fluid flow. The model used simulated subarachnoid pressures from healthy controls (N = 9), Chiari patients with (N = 7) and without (N = 8) syringomyelia. A parametric analysis was conducted to determine how features of the arterial pulse altered flow. The features of interest included: the timing and magnitude of the peak displacement, and the area under the curve in the phases of uptake and decline. A secondary aim was to determine if the previously observed differences between subject groups were sensitive to variation in the arterial pulse wave. The study demonstrated that the Chiari patients without a syrinx maintained a significantly higher level of perivascular inflow over a physiologically likely range of pulse wave shapes. The analysis also suggested that age-related changes in the arterial pulse (i.e. increased late systolic pulse amplitude and faster diastolic decay), could increase resistance to perivascular inflow affecting solute transport.     

Effect of surface roughness on squeeze film poroelastic bearings with special reference to synovial joints

A simplified mathematical model has been developed for understanding the combined effects of surface roughness and couple stresses on lubrication aspects of synovial joints. The modified Reynolds equation which incorporates the elastic as well as randomized surface roughness structure of cartilage with couple-stress fluid as lubricant is derived. The mean pressure, load carrying capacity and time of approach as functions of film thickness during normal articulation of joints are obtained by using Christensen stochastic theory with the assumption that the roughness asperity heights are to be small compared to the film thickness. The effects of surface roughness and elasticity are considerably pronounced for the poroelastic bearings with couple-stress fluid as lubricant compared with classical case.     

Changes in cell surface primary cilia and microvilli concurrent with measurements of fluid flow across the rabbit corneal endothelium ex vivo

Primary cilia and microvilli have been reported on the mammalian rabbit corneal endothelium but their relationship to cell function is undefined. Six corneas from healthy 2 kg female albino rabbits were glutaraldehyde-fixed post mortem (15:00 h) or twelve corneal stroma-endothelial preparations incubated at 37 degrees C under an applied hydrostatic pressure of 20 cm H2O for 4 h prior to fixation. The corneal endothelium was assessed by quantitative scanning electron microscopy. Cells fixed immediately post mortem were decorated with small stubby microvilli (average 21 +/- 13/100 micron 2), and only 25% of the cells were decorated with primary cilia having an average length of 2.44 +/- 1.56 microns. Following 4 h ex vivo incubation with a phosphate-buffered Ringer solution, conspicuous microvilli developed to an average density of 40 +/- 19/100 micron 2 and primary cilia were found on 12% of the cells, having on average length of 2.27 +/- 1.38 microns. Following 4 h incubation in a bicarbonate-buffered Ringer solution, small stubby microvilli developed to a density of 49 +/- 18/100 micron 2, and 40% of the cells showed primary cilia with an average length of 4.31 +/- 1.93 microns; the net trans-endothelial fluid flow in the latter set was 60% greater. These studies indicate that the primary cilia on corneal endothelial cells might be responsive to fluid flow, but that mild mechanical and/or chemical stress could also be the cause of the change since the elaboration of primary cilia can be accompanied by microvilli as well.     

Characterization of flow conditions in 2 L and 20 L wave bioreactors® using computational fluid dynamics

Characterization of flow conditions is of great importance to control cell growth and cell damage in animal cell culture because cell viability is influenced by the flow properties in bioreactors. Alternative reactor types like Wave Bioreactors® have been proposed in recent years, leading to markedly different results in cell growth and product formation. An advantage of Wave Bioreactors® is the disposability of the Polyethylenterephthalet‐bags after one single use (fast setup of new production facilities). Another expected advantage is a lower shear stress compared to classical stirred‐tank reactors, due to the gentle liquid motion in the rocking cellbag. This property would considerably reduce possible cell damage. The purpose of the present study is to investigate in a quantitative manner the key flow properties in Wave Bioreactors®, both numerically and experimentally. To describe accurately flow conditions and shear stress in Wave Bioreactors® using numerical simulations, it is necessary to compute the unsteady flow applying Computational Fluid Dynamics (CFD). Corresponding computations for two reactor scales (2 L and 20 L cellbags) are presented using the CFD code ANSYS‐FLUENT®. To describe correctly the free liquid surface, the present simulations employ the Volume of Fluid (VOF) method. Additionally, experimental measurements have been carried out to determine liquid level, flow velocity and liquid shear stress, which are used as a validation of the present CFD simulations. It is shown that the obtained flows stay in the laminar regime. Furthermore, the obtained shear stress levels are well below known threshold values leading to damage of animal cells. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010     

A novel solution for fluid flow problems based on the lattice Boltzmann method

Recently, phase separation and fluid flow problems have represented an important development in fluid dynamics, which has many important industrial applications. Lattice Boltzmann method (LBM) is the numerical method that explains the behaviour of fluid dynamics in mesoscopic scale single-component single-phase and multi-component multiphase flows. In this paper, we study the lattice Boltzmann models (LBMs) in two dimensions (2D) with nine directions (Q9), that is the D2Q9 model was used to study the phase separation and observe that the phenomenon of fluid flow in a cylinder has obstacle and square cavity. The simulation results show that fluid flows in the square cavity and in the cylinder, present phase separation of single-component multiphase fluid flow.     

The influence of medication on salivary flow of the elderly: preliminary study

doi:10.1111/j.1741‐2358.2009.00326.x
The influence of medication on salivary flow of the elderly: preliminary study Objective: This study was to evaluate the influence of medications on unstimulated and stimulated salivary flow in elderly men and women. Background: Several diseases and conditions are associated with decreasing salivary flow. Medications can be risk factors for hyposalivation due to the effect particular drug categories. Methods: Seventy‐five elderly of both gender (sixty years old or over) from the Geriatric Dental Clinic at the Federal Fluminense University Dental School, were interviewed about their health status and chronic use of medication. After the interview, unstimulated and stimulated saliva were collected from each subject. The collection time was five minutes, and the flow rate was calculated as ml/min. Results: The mean unstimulated salivary flow was 0.25 ml/min for women and 0.30 ml/min for men, while the mean for stimulated salivary flow was 1.23 ml/min for women and 1.31 ml/min for men, without both differences being non‐significant (p > 0.05). The difference between the mean production of unstimulated and stimulated salivary flow was statistically significant, regardless of gender (p < 0.01). A significant reduction of stimulated salivary flow was observed with the usage of cardiovascular agents (p < 0.05). Conclusion: Drugs used in cardiovascular disease influence the flow of stimulated saliva.     

Effect of surface roughness of Ti, Zr, and TiZr on apatite precipitation from simulated body fluid

Some of the critical properties for a successful orthopedic or dental implant material are its biocompatibility and bioactivity. Pure titanium (Ti) and zirconium (Zr) are widely accepted as biocompatible metals, due to their non-toxicity. While the bioactivity of Ti and some Ti alloys has been extensively investigated, there is still insufficient data for Zr and titanium-zirconium (TiZr) alloys. In the present study, the bioactivity, that is, the apatite forming ability on the alkali and heat treated surfaces of Ti, Zr, and TiZr alloy in simulated body fluid (SBF), was studied. In particular, the effect of the surface roughness characteristics on the bioactivity was evaluated for the first time. The results indicate that the pretreated Ti, Zr and TiZr alloy could form apatite coating on their surfaces. It should be noted that the surface roughness also critically affected the bioactivity of these pretreated metallic samples. A surface morphology with an average roughness of approximately 0.6 microm led to the fastest apatite formation on the metal surfaces. This apatite layer on the metal surface is expected to bond to the surrounding bones directly after implantation.