bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermomechanical analysis of collagen crosslinking in the developing ovine thoracic aorta
Authors: Wells Sarah M. , Adamson S. Lee , Langille B. Lowell , Lee J. Michael
Published: November 2024

We have used hydrothermal isometric tension (HIT) techniques in a sheep model to assess collagen crosslink stability and its contribution to the mechanical properties of the ovine thoracic aorta during perinatal and postnatal development. Aortic tissue was studied from fetal sheep, lambs, and adult sheep. Strips of tissue were loaded under isometric tension and heated to a 90 $^{\circ}$ C isotherm which was sustained for 3 hours. The decrease in load at this temperature is associated with collagen peptide bond hydrolysis and chain slippage, and the rate of this decrease is an inverse indicator of collagen crosslinking. The half‐time of load decay ( $t_{1/2}$ ) was computed before and after tissue was treated with NaBH $_{4}$ which stabilizes immature, reducible crosslinks. We observed a two‐fold increase in $t_{1/2}$ of untreated tissue from the lamb to the adult, indicating that aortic collagen crosslinking increased during postnatal development. Furthermore, the $t_{1/2}$ of NaBH $_{4}$ ‐stabilized lamb tissue was similar to that of the untreated adult tissue, suggesting that much of the immature crosslinking in the lamb is stabilized during postnatal development. These observations suggest (a) increased crosslinking occurs during postnatal development and (b) that this increase is largely due to a conversion of immature crosslinks into their mature, heat stable form.
Mechanical characteristics of the canine thoracic duct: what are the driving forces of the lymph flow?
Authors: Deng Xiaoyan , Marinov Gueorgui , Marois Yves , Guidoin Robert
Published: November 2024

This study is designed to better understand the mode of lymph transport, particularly through the extrinsic pumping by external compression of the lymph vessel. The pressure‐diameter relationship of lymphatic segments isolated from the canine thoracic duct was examined using a laser optical micrometer measurement system. Results revealed that the thoracic duct displayed a high extensibility or compliance in the physiological pressure range, yet became progressively less so with increasing internal pressure. The calculated incremental circumferential modulus of the thoracic duct under physiological pressure (range of 2 to 6 cm H $_{2}$ O) showed values ranging from 1.2 × 10 $^{4 }$ to 3.61 × 10 $^{5}$ dyn/cm $^{2}$ . At a pressure of 35 cm H $_{2}$ O, the modulus reached a limiting value of approximately 6.0 ×10 $^{6}$ dyn/cm $^{2}$ . In the physiological pressure range, the relative wall thickness ( $h/R_\mathrm{o}$ ) of the canine thoracic duct was approximately 3.5%, which was much lower than that reported for canine arterial segments and similar in value to that of the canine jugular vein. In conclusion, the pressure‐diameter curve of the canine thoracic duct was shown to resemble that of venous vessels. However, the circumferential elastic modulus of the thoracic duct wall was lower than the moduli of veins, proving that lymphatics are more compliant than veins. This suggests lymph flow in the thoracic duct may be better promoted by external compression of the lymphatic vessel.
Frictional behaviour of bovine articular cartilage
Authors: Jin Z.M. , Pickard J.E. , Forster H. , Ingham E. , Fisher J.
Published: November 2024

The experimentally measured indentation displacement and friction of normal and degraded (treated with chondroitinase AC) bovine articular cartilage plugs against a smooth steel plate were compared with the predictions based on the biphasic theory using the finite element method. It was found that the measured indentation displacement of both cartilage specimens could be predicted from the biphasic theory and the permeability for the degraded cartilage specimen was increased approximately three times. However, the measured friction coefficient was much lower for short period of loading, and the difference in the finite element prediction of friction coefficient between the normal and degraded cartilage specimens was not observed in the experiment. Therefore, it was concluded that both biphasic and other mechanisms were important in controlling the frictional and lubricating characteristics of articular cartilage in mixed and boundary lubrication regimes.
Effects of diacerein on biosynthesis activities of chondrocytes in culture
Authors: Pujol J.‐P. , Felisaz N. , Boumediene K. , Ghayor C. , Herrouin J.‐F. , Bogdanowicz P. , Galera P.
Published: November 2024

The maintenance of articular cartilage integrity requires a balance between anabolic and catabolic processes which are under the control of chondrocytes. These cells are living in an anaerobic environment and normally do not divide. They are responsible for the continuous maintenance of the cartilage extracellular matrix (ECM). Although multiple factors are involved in the dynamic homeostasis of cartilage, increases in cytokines such as interleukin‐1 (IL‐1) are associated with a decrease in synthesis and an increase in degradation of the proteoglycans and collagens. Conversely, growth factors such as transforming growth factor‐β (TGF‐β) stimulate chondrocyte synthesis of collagens and proteoglycans, and reduce the activity of IL‐1 stimulated metalloproteases, thus opposing the inhibitory and catabolic effects of IL‐1. By its capability to reduce IL‐1 effects and to stimulate TGF‐β expression in cultured articular chondrocytes, diacerein could favour anabolic processes in the OA cartilage and, hence may contribute to delay the progression of the disease.
Computer simulation of osmotic expansion and shrinkage in okra hypocotyl segments
Authors: Yamamoto Ryoichi , Fujii Shuhei , Tanimoto Eiichi , Nevins Donald J.
Published: November 2024

Okra hypocotyl segments were incubated in solutions of 0.3 or 0.4 M sorbitol at various temperatures and their shrinkage was measured. The result yielded an apparent activation energy for shrinkage of 4.8 kcal/mol, which is close to that of the viscosity of water. This coincidence suggests that the viscosity of water, i.e., the reciprocal function of water conductivity, is a limiting factor for osmotic shrinkage. Abrasion of okra hypocotyl segments with Carborundum substantially increased the rate of their osmotic shrinkage, indicating that the cuticle is the major barrier to water uptake by segments. The apparent activation energy for osmotic shrinkage was 4.5 kcal/mol in abraded segments. By introducing water conductivity into an algorithm, osmotic shrinkage and expansion of hypocotyl segments was successfully predicted by computation with this algorithm. Hence the extent of the contribution of water conductivity in osmotic shrinkage and expansion can be evaluated. Based on this simulation, water conductivity was identified as one of the major factors in governing the elongation growth rate of cells along with the osmotic pressure of the cell sap and the mechanical properties of the cell wall.
Computational fluid dynamic studies of leukocyte adhesion effects on non‐Newtonian blood flow through microvessels
Authors: Das B. , Johnson P.C. , Popel A.S.
Published: November 2024

The study of the effect of leukocyte adhesion on blood flow in small vessels is of primary interest to understand the resistance changes in venular microcirculation. Available computational fluid dynamic studies provide information on the effect of leukocyte adhesion when blood is considered as a homogeneous Newtonian fluid. In the present work we aim to understand the effect of leukocyte adhesion on the non‐Newtonian Casson fluid flow of blood in small venules; the Casson model represents the effect of red blood cell aggregation. In our model the blood vessel is considered as a circular cylinder and the leukocyte is considered as a truncated spherical protrusion in the inner side of the blood vessel. The cases of single leukocyte adhesion and leukocyte pairs in positions aligned along the same side, and opposite sides of the vessel wall are considered. The Casson fluid parameters are chosen for cat blood and human blood and comparisons are made for the effects of leukocyte adhesion in both species. Numerical simulations demonstrated that for a Casson fluid with hematocrit of 0.4 and flow rate $Q=0.072$ nl/s, a single leukocyte increases flow resistance by $5$ % in a 32 μm diameter and 100 μm long vessel. For a smaller vessel of 18 μm, the flow resistance increases by 15%.
Detection of red cell aggregation by low shear rate viscometry in whole blood with elevated plasma viscosity
Authors: Janzen Johan , Elliott Thomas G. , Carter Cedric J. , Brooks Donald E.
Published: November 2024

The viscosity of whole blood measured at low shear rates is determined partly by shear resistance of the red cell aggregates present, stronger aggregation increasing the viscosity in the absence of other changes. Effects of cell deformability can confound interpretation and comparison in terms of aggregation, however, particularly when the plasma viscosity is high. We illustrate the problem with a comparison of hematocrit‐adjusted blood from type 1 diabetes patients and controls in which it is found the apparent and relative viscosities at a true shear rate of 0.20 s $^{-1}$ are lower in the patient samples than age matched controls, in spite of reports that aggregation is increased in such populations. Because the plasma viscosities of the patients were higher on average than controls, we performed a series of experiments to examine the effect of plasma protein concentration and viscosity on normal blood viscosity. Dilution or concentration by ultrafiltration of autologous plasma and viscosity measurements at low shear on constant hematocrit red cell suspensions showed (a) suspension viscosity at 0.25 and 3 s $^{-1}$ increased monotonically with plasma protein concentration and viscosity but (b) the relative viscosity increased, in concert with the microscopic aggregation grade, up to a viscosity of approximately 1.25 mPa‐s but above this the value the relative viscosity no longer increased as the degree of aggregation increased in concentrated plasmas. It is suggested that in order to reduce cell deformation effects in hyperviscous pathological plasmas, patient and control plasmas should be systematically diluted before hematocrit is adjusted and rheological measurements are made. True shear rates should be calculated. Comparison of relative viscosities at low true shear rates appears to allow the effects of red cell aggregation to be distinguished by variable shear rate viscometry in clinical blood samples.
Rheological evidence of the gelation behavior of hyaluronan–gellan mixtures
Authors: Mo Yunqian , Kubota Kenji , Nishinari Katusyoshi
Published: November 2024

It was found that solutions of calcium hyaluronate (CaHA) (0.1∼0.5 wt%) could form a gel by mixing with solutions of sodium type gellan (0.1∼0.5 wt%), although neither polymer by itself forms a gel at low concentrations (0.1∼0.5 wt% in this experiment). The rheological properties of CaHA–gellan mixtures were investigated by dynamic and steady shear measurements. Both storage shear modulus G′ and loss shear modulus G″ for CaHA–gellan mixtures increased with increasing time, and tended to an equilibrium value after 1 h. After reaching steady values of G′ and G″, the frequency dependence of G′ and G″ was observed. G′ was always larger than G″ in the accessible frequency range from 10−2 to 102 rad/s. The effects of pH and calcium ions were examined. Gel formation of the mixtures was promoted by decreasing pH and adding from 0.01 to 0.1 M calcium ions, but excessive calcium ions weakened the gel.
Osmotic fragility of the erythrocyte membrane: characterization by modeling of the transmittance curve as a function of the NaCl concentration
Authors: Didelon J. , Mazeron P. , Muller S. , Stoltz J.F.
Published: November 2024

The theoretical extinction of blood suspensions submitted to a slow dialysis is analyzed in terms of their NaCl concentration. The model involves two adjustable parameters, χ and K, related to swelling and hemolysis. During swelling, the erythrocyte volume is supposed to vary linearly with the saline concentration. During hemolysis, an exponential decay of the hemoglobin concentration in the erythrocyte is used. The theoretical transmittance curves are consistent with the measurements carried out at a wavelength of 0.808 μm on native and incubated blood samples. χ and K are relevant parameters to characterize quantitatively the fragility of the erythrocyte membrane. The effect of a non ideal character of the hemoglobin solutions and of normal distributions of χ and K is also discussed.
Rheological effects of red blood cell aggregation in the venous network: A review of recent studies
Authors: Bishop Jeffrey J. , Popel Aleksander S. , Intaglietta Marcos , Johnson Paul C.
Published: November 2024

It has long been recognized that understanding the rheological properties of blood is essential to a full understanding of the function of the circulatory system. Given the difficulty of obtaining carefully controlled measurements in vivo, most of our current concepts of the flow behavior of blood in vivo are based on its properties in vitro. Studies of blood rheology in rotational and tube viscometers have defined the basic properties of blood and pointed to certain features that may be especially significant for understanding in vivo function. At the same time, differences between in vivo and in vitro systems combined with the complex rheological properties of blood make it difficult to predict in vivo blood rheology from in vitro studies. We have investigated certain flow properties of blood in vivo, using the venular network of skeletal muscle as our model system. In the presence of red blood cell aggregation, venous velocity profiles become blunted from the parabolic as in Poiseuille flow, as pseudo‐shear rate (= mean fluid velocity/vessel diameter) is decreased from ∼100 s−1 to 5 s−1. At control flow rates, the short distance between venular junctions does not appear to permit significant axial migration and red cell depletion of the peripheral fluid layer before additional red cells and aggregates are infused from a feeding tributary. Formation of a cell‐free plasma layer at the vessel wall and sedimentation in vivo are evident only at very low pseudo‐shear rates (<5 s−1). These findings may explain in large part observations in whole organs of increased venous resistance with reduction of blood flow.
Mechanotransduction in endothelial responses to shear stress: Review of work in Dr. Chien's laboratory
Authors: Shyy John Y.‐J.
Published: November 2024

Shear stresses play an important role in vascular biology in health and disease. While disturbed flows with low shear stresses in the bends and bifurcations of the arterial tree are atherogenic, laminar flows with high shear stresses in the straight part of the vessel is atheroresistant. Thus, elucidation of the mechanotransduction mechanism in vascular endothelial cells in response to shear stress has become an important research topic among bioengineers and vascular biologists. Here is a summary of studies performed in Dr. Shu Chien's laboratory on shear stress‐induced signal transduction and gene expression during the period from 1992–1999. These studies, together with efforts from other research groups, demonstrate that integrins, which are transmembrane molecules that interact with both extracellular matrices and intracellular cytoskeleton and kinases in the focal adhesions, are important in mechanotransduction. This hypothesis is mainly supported by the similarity between cellular and molecular events elicited by shear stress and those activated during the integrin‐mediated cell attachment to extracellular matrices. Evidence is also provided to show that the dynamic and specific interaction between integrin and extracellular matrices is essential for mechanotransduction.
Measurement temperature plays a pivotal role in the distribution of erythrocyte deformability after LPS
Authors: Jagger Justin E. , Ellis Christopher G. , Sibbald William J. , Eichelbrönner Otto
Published: November 2024

Reductions in red blood cell membrane deformability (RBCD) may perturb microcirculatory blood flow and impair tissue O2‐availability. We investigated the effect of assay temperature on the distribution of RBCD in endotoxin (LPS) incubated and control RBCs. Fresh blood from healthy rats was incubated with and without the presence of LPS for 6 hrs. An index of red blood cell membrane deformability, δ, was measured via the micropipette aspiration technique at 25°C and 37°C at 0, 2 and 6 hrs of incubation. The ATP content of RBC was measured by the luciferin–luciferase technique. At 25°C, LPS caused a significant decrease in mean δ after 2 and 6 hours incubation compared to controls (−10.0%, p=0.03 and −24.0%, p=0.03, respectively) characterized by a left shift in the distribution (skewness: −1.4). However, at 37°C a significant decrease in δ was only detected after 6 hrs of LPS incubation (−13.8%, p=0.01, compared to −5.1%, p=0.7 at 2 hours) and lacked the left shifted distribution (skewness: 0.2). No significant difference in ATP content of RBCs was observed between groups. We have shown that LPS incubation results in a significant decrease in RBCD and that room temperature measurement of physical membrane properties may exaggerate the differences between normal and perturbed RBCs.
Proteoglycan deposition around chondrocytes in agarose culture: Construction of a physical and biological interface for mechanotransduction in cartilage
Authors: Quinn T.M. , Schmid P. , Hunziker E.B. , Grodzinsky A.J.
Published: November 2024

With a view towards the development of methods for cartilage tissue engineering, matrix deposition around individual chondrocytes was studied during de novo matrix synthesis in agarose suspension culture. At a range of times in culture from 2 days to 1 month (long enough for cartilage‐like material properties to begin to emerge), pericellular distributions of proteoglycan and matrix protein deposition were measured by quantitative autoradiography, while matrix accumulation and cell volumes were estimated by stereological methods. Consistent with previous work, tissue‐average rates of matrix synthesis generally decreased asymptotically with time in culture, as de novo matrix accumulated. Cell‐scale analysis revealed that this evolution was accompanied by a transition from predominantly pericellular matrix (within a few μm from the cell membrane) deposition early in culture towards proteoglycan and protein deposition patterns more similar to those observed in cartilage explants at later times. This finding may suggest a differential recruitment of different proteoglycan metabolic pools as matrix assembly progresses. Cell volumes increased with time in culture, suggestive of alterations in volume regulatory processes associated with changes in the microphysical environment. Results emphasize a pattern of de novo matrix construction which proceeds outward from the pericellular matrix in a progressive fashion. These findings provide cell‐scale insight into the mechanisms of assembly of matrix proteins and proteoglycans in de novo matrix, and may aid in the development of tissue engineering methods for cartilage repair.
The effects of pressure on chondrocyte tumour necrosis factor receptor expression
Authors: Westacott C.I. , Urban J.P.G. , Goldring M.B. , Elson C.J.
Published: November 2024

This work was performed to determine whether one aspect of load, pressure, could alter tumour necrosis factor (TNF) receptor type I (RI) expression on chondrocytes. Encapsulated tsT/AC62, osteoarthritic (OA) or non‐arthritic (NA) chondrocytes were centrifuged at speeds representing 5 or 20 MPa, incubated for specific periods, released from alginate and TNFRI and II (TNFRII) expression determined by flow cytometry. Significant (p<0.05, n=4) changes in tsT/AC62 chondrocyte TNFRI expression were apparent 24 hours after application of 20 MPa. Five or 20 MPa increased OA chondrocyte TNFRI expression; chondrocytes from some OA patients were markedly sensitive to 20 MPa. NA chondrocyte TNFRI expression usually decreased in response to 5 and 20 MPa. Significant pressure‐induced differences in TNFRI expression between NA and OA groups were apparent at 5, but not 20 MPa. Pressure did not significantly alter TNRFII expression on tsT/AC62, NA or OA chondrocytes. These results suggest a mechanism whereby sensitivity of chondrocytes to the effects of TNFα may be increased, in susceptible individuals, in regions of the joint that experience peak loading.
Nitric oxide (NO) and cartilage metabolism: NO effects are modulated by superoxide in response to IL‐1
Authors: Jouzeau Jean‐Yves , Pacquelet Sandrine , Boileau Christelle , Nedelec Emmanuelle , Presle Nathalie , Netter Patrick , Terlain Bernard
Published: November 2024

Nitric oxide (NO) is thought to mediate most effects of interleukin‐1 (IL‐1) on cartilage. In vitro evidence includes the decreased synthesis of extracellular matrix components, the abnormal cell renewal, the decreased production of IL‐1 receptor antagonist, the induction of apoptosis and the enhanced sensitivity of chondrocytes to oxidative stress. Studies in NOS2−/− mice or administration of NO synthase inhibitors in animal models of joint disorders have confirmed its potent pathophysiological role in cartilage. Using L‐NMMA (1 mM), as a NO synthase inhibitor, and CuDips (10 μM), as a SOD mimetic, we provide evidence that the inhibitory potency of IL‐1β on proteoglycan synthesis and its stimulating effect on COX‐2 activity depend both on NO and O2 −. production. Peroxynitrite formation is further demonstrated by the occurrence of 3‐nitrotyrosines in chondrocytes stimulated in vitro with 2.5 ng/ml IL‐1 and in femoral condyles of rats injected locally with 1 μg IL‐1. Preliminary data suggest that such contribution of reactive oxygen species is not shared in common by IL‐17, another NO‐producing cytokine. We conclude that superoxide is a key modulator of NO‐mediated effects in chondrocyte stimulated with IL‐1 and that a combined therapy with NO synthase inhibitors and antioxidants may be promising for a full cartilage protection.
Animal models of osteoarthritis
Authors: Brandt Kenneth D.
Published: November 2024

Animal models have proved to be of considerable importance in elucidating mechanisms underlying joint damage in osteoarthritis (OA) and providing proof of concept in the development of pharmacologic and biologic agents that may modify structural damage in the OA joint. The utility of animal models in predicting the response to an intervention with a drug or biologic agent in humans, however, can be established only after evidence is obtained of a positive effect of the agent in humans. To date, no agent has been shown unequivocally to have such an effect, although diacerhein and glucosamine have recently been reported to lower the rate of loss of articular cartilage in patients with hip OA and knee OA, respectively, based on measurements of the rate of joint space narrowing in plain radiographs. Furthermore, the predominant manifestation of OA – and the feature that leads people with radiographic changes of the disease to decide to seek medical attention and contributes to the enormous medicoeconomic and socioeconomic burden imposed by the disease – is joint pain. Notably, none of the animal models of OA is a good indicator of the analgesic effects of pharmacologic agents. Indeed, it should not be assumed a priori that reduction in the rate of progression of joint damage in OA will be associated with a reduction in joint pain.
Differential gene expression analysis in a rabbit model of osteoarthritis induced by anterior cruciate ligament (ACL) section
Authors: Bluteau G. , Gouttenoire J. , Conrozier T. , Mathieu P. , Vignon E. , Richard M. , Herbage D. , Mallein‐Gerin F.
Published: November 2024

Osteoarthritis (OA) is the most common of all joint diseases to affect mankind and is characterized by the degradation of articular cartilage. The low availability of normal and pathologic human cartilage and the inability to study the early stages of the disease in humans has led to the development of numerous animal models of OA. The aim of our study was to establish gene expression profiles during the progression of a rabbit model of OA induced by anterior cruciate ligament (ACL) section. Semiquantitative RT–PCR was used to follow expression of several relevant molecules (type II and X collagens, aggrecan, osteonectin, βig‐h3, BiP, TIMP‐1, MMP‐1, ‐3, ‐13, aggrecanase‐1, ‐2) during development of OA in articular cartilage. In parallel, we monitored the activities of collagenase, caseinase, phospholipase A2 and glycosyltransferases (xylosyl‐, galactosyl‐, glucuronyl‐ and N‐acetyl‐galactosaminyl‐transferase). Novel cDNA clones for rabbit type X collagen, aggrecanase‐1 and ‐2, osteonectin and BiP were constructed to obtain species‐specific primers. Ours result show that MMP‐13 (collagenase‐3) gene expression increased dramatically early after ACL surgery and remained high thereafter. An increase in MMP‐1 (collagenase‐1) and MMP‐3 expression was also noted with an absence of variation for TIMP‐1 expression. In addition, the global MMPs activities paralleled the MMP gene expression. These data together characterize at the molecular level the evolution of OA in this rabbit model. Furthermore, we have undertaken a search for identifying differentially expressed genes in normal and OA cartilage in this model, by differential display RT–PCR. We present here preliminary results with the determination of the best technical conditions to obtain reproducible electrophoresis patterns of differential display RT–PCR.
Bioreactor studies of native and tissue engineered cartilage
Authors: Vunjak‐Novakovic G. , Obradovic B. , Martin I. , Freed L.E.
Published: November 2024

Functional tissue engineering of cartilage involves the use of bioreactors designed to provide a controlled in vitro environment that embodies some of the biochemical and physical signals known to regulate chondrogenesis. Hydrodynamic conditions can affect in vitro tissue formation in at least two ways: by direct effects of hydrodynamic forces on cell morphology and function, and by indirect flow‐induced changes in mass transfer of nutrients and metabolites. In the present work, we discuss the effects of three different in vitro environments: static flasks (tissues fixed in place, static medium), mixed flasks (tissues fixed in place, unidirectional turbulent flow) and rotating bioreactors (tissues dynamically suspended in laminar flow) on engineered cartilage constructs and native cartilage explants. As compared to static and mixed flasks, dynamic laminar flow in rotating bioreactors resulted in the most rapid tissue growth and the highest final fractions of glycosaminoglycans and total collagen in both tissues. Mechanical properties (equilibrium modulus, dynamic stiffness, hydraulic permeability) of engineered constructs and explanted cartilage correlated with the wet weight fractions of glycosaminoglycans and collagen. Current research needs in the area of cartilage tissue engineering include the utilization of additional physiologically relevant regulatory signals, and the development of predictive mathematical models that enable optimization of the conditions and duration of tissue culture.
Prediction of LDL concentration at the luminal surface of a vascular endothelium
Authors: Wada Shigeo , Karino Takeshi
Published: November 2024

To find out whether concentration polarization of low‐density lipoprotein (LDL) occurs at the surface of a vascular endothelium or not, transport of LDL in flowing blood to an water‐permeable endothelium was studied theoretically by means of CFD. Calculations were carried out for an endothelium exposed to a Couette flow by assuming that the surface geometry of the endothelium could be expressed by a cosine function. Two typical cases were considered for the permeability of endothelium to water; one was uniform permeability everywhere in the endothelium, and the other was uneven permeability which was augmented at the intercellular junction. It was found that, in both cases, the surface concentration of LDL increased in going distally from the entrance, taking locally high and low values at the valleys and hills of the endothelium, respectively, and the variation was larger in the case of endothelium with uneven permeability. These results clearly showed that concentration polarization of LDL which might affect the uptake of LDL by the arterial wall certainly occurs at the surface of the endothelium even if the flow is disturbed microscopically by the uneven surface of the endothelium.
Parallel‐plate flow chamber for studies of 3D flow–endothelium interaction
Authors: Watkins N.V. , Caro C.G. , Wang W.
Published: November 2024

Flow induced shear stress influences vascular cellular biology and pathophysiology in numerous ways. Previous in vitro studies on interactions between flow and endothelial cells using parallel‐plate flow chambers involve two‐dimensional flows, whereas flows in larger vessels are commonly three‐dimensional. We have constructed a parallel plate flow chamber with a backward facing step aligned oblique to the axis of the chamber. Flow visualisation by steady injection of ink through a hypodermic tube reveals swirling flow in the recirculation region downstream of the step. At given angles of the step, θ (to the axis of the chamber), the pitch of the swirl and the width of the separation region, as measured in the direction perpendicular to the step, increase with the Reynolds number (Re). On the other hand, at given values of Re, reduction of θ results in increases in the swirl pitch but decreases in the width of the separation zone. Furthermore, clearance time of ink from the separation region is shorter with an oblique step than a perpendicular one at given Re. Computer simulation confirms the 3D swirling flow created by the oblique step and provides detailed distribution of wall shear stresses in the flow chamber.
Residence times and basins of attraction for a realistic right internal carotid artery with two aneurysms
Authors: Butty V.D. , Gudjonsson K. , Buchel P. , Makhijani V.B. , Ventikos Y. , Poulikakos D.
Published: November 2024

We are presenting computational fluid dynamics simulation results for the flow in an anatomically accurate right internal carotid artery, exhibiting two saccular aneurysms close to each other. Our study focuses on the investigation of passage times for blood cells through the two‐aneurysm malformation. We construct residence time maps that exhibit strong non‐uniformity, linked to the entry of fluid in only the first, only the second, or in both aneurysms. An entrance index is computed, showing qualitatively the regions at an arterial section upstream of the aneurysms, where cells following one of these scenarios emanate. The significance of the residence time profiles and entry scenarios obtained is discussed with respect to thrombosis and pharmacokinetics. Preliminary evidence that the inflow–outflow patterns of the two aneurysms may be leading to particularly complex flow and to chaotic mixing is discussed.
The geometry of unstented and stented pig common carotid artery bypass grafts
Authors: Caro Colin , Jeremy Jamie , Watkins Nick , Bulbulia Richard , Angelini Gianni , Smith Frank , Wan Song , Yim Anthony , Sherwin Spencer , Peiró Joaquim , Papaharilaou Yannis , Falzon Brian , Giordana Sergio , Griffiths Clydd
Published: November 2024

The long‐term success of arterial bypass grafting with autologous saphenous veins is limited by neointimal hyperplasia (NIH), which seemingly develops preferentially at sites where hydrodynamic wall shear is low. Placement of a loose‐fitting, porous stent around end‐to‐end, or end‐to‐side, autologous saphenous vein grafts on the porcine common carotid artery has been found significantly to reduce NIH, but the mechanism is unclear. In a preliminary study, we implanted autologous saphenous vein grafts bilaterally on the common carotid arteries of pigs, placing a stent around one graft and leaving the contralateral graft unstented. At sacrifice 1 month post implantation, the grafts were pressure fixed in situ and resin casts were made. Unstented graft geometry was highly irregular, with non‐uniform dilatation, substantial axial lengthening, curvature, kinking, and possible long‐pitch helical distortion. In contrast, stented grafts showed no major dilatation, lengthening or curvature, but there was commonly fine corrugation, occasional slight kinking or narrowing of segments, and possible long‐pitch helical distortion. Axial growth of grafts against effectively tethered anastomoses could account for these changes. CFD studies are planned, using 3D MR reconstructions, on the effects of graft geometry on the flow. Abnormality of the flow could favour the development of vascular pathology, including NIH.
Large deformation shear properties of liver tissue
Authors: Liu Zizhen , Bilston Lynne E.
Published: November 2024

Characterization of the mechanical properties of soft biological tissues is important for establishing the mechanical tolerances of the tissues, and for input to computational models. In this work, the viscoelastic properties of bovine liver tissue in shear loading have been measured using relaxation and constant shear rate loading. The tissue is nonlinearly viscoelastic for strains greater than 0.2%, has a yield strain of approximately 10, and shows moderate strain‐rate sensitivity. The response can be modelled using a nonlinear viscoelastic differential model previously developed for brain tissue.
Caveolin‐1 redistribution in human endothelial cells induced by laminar flow and cytokine
Authors: Sun R.J. , Muller S. , Zhuang F.Y. , Stoltz J.F. , Wang X.
Published: November 2024

Caveolin‐1 is a principal component of caveolae and is involved in signaling transduction in a number of cells. A hypothesis was proposed in this work that mechanical forces due to flow induce caveolin‐1 translocation. So the changes of caveolin‐1 expression and distribution in cultured endothelial cells (HUVECs) exposed to a steady laminar flow were studied. For comparing with the influence of cytokine, caveolin‐1 in the cells stimulated by TNF‐α was also investigated. Indirect immunofluorescence and double fluorescence labeling showed that in control cells, caveolin‐1 was primarily localized on the cell surface, which corresponded to the peripheral distribution of F‐actin, and presented some local concentrations. In the cells exposed to a laminar flow (1.0 Pa), caveolin‐1 distribution showed a time‐dependent variation. After 24 h of shear, the local concentration of caveolin‐1 was found, in the most cells, at upstream side of cell body. Also more caveolin‐1 molecules were observed in the cells. In contrast, TNF‐α induced a decrease of caveolin‐1 in cells. The redistribution of caveolin‐1 seems to be correlated to F‐actin organization.
Mechanosensitivity and intercellular communication in HOBIT osteoblastic cells: A possible role for gap junction hemichannels
Authors: Romanello Milena , Veronesi Valentina , D'Andrea Paola
Published: November 2024

Mechanically induced intercellular Ca2+ signalling was investigated in differentiated HOBIT osteoblastic cells. HOBIT cells express connexin43 clustered at the cell‐to‐cell boundary and display functional intercellular coupling assessed by intercellular transfer of Lucifer yellow. Mechanical stimulation of single cells, besides leading to an intracellular Ca2+ rise, induced a wave of increased Ca2+ that was radially propagated to surrounding cells. Treatment of cells with thapsigargin blocked mechanically induced signal propagation. Intercellular Ca2+ spreading was inhibited by 18α‐glycyrrhetinic acid, demonstrating the involvement of gap junctions in signal propagation. Suramin and apyrase decreased the extent of wave propagation, suggesting that ATP‐mediated paracrine stimulation contribute to cell‐to‐cell signalling. The functional expression of gap‐junctional hemichannels was evidenced in experiments of Mn2+ quenching, extracellular dye uptake and intracellular Ca2+ release, activated by uptake of inositol 1,4,5‐trisphosphate from the external medium. Gap‐junctional hemichannels were activated by low extracellular Ca2+ concentrations and inhibited by 18α‐glycyrrhetinic acid.
Experimental tests of the cellular tensegrity hypothesis
Authors: Stamenović Dimitrije , Mijailovich Srboljub M. , Tolić‐Nørrelykke Iva Marija , Wang Ning
Published: November 2024

The tensegrity model depicts the cytoskeleton (CSK) as a prestressed network of interconnected filaments. The prestress is generated by the CSK contractile apparatus and is partly balanced by traction at the cell–substrate interface and partly by CSK internal compression elements such as microtubules (MTs). A key feature of tensegrity is that the shear modulus (G) must increase in proportion with the prestress. Here we have tested that prediction as well as the idea that compression of MTs balance a portion of the cell prestress. Airway smooth muscle cells were studied. Traction microscopy was used to calculate traction. Because traction must be balanced by the stress within the cell, the prestress could be computed. Cell G was measured by oscillatory magnetic cytometry. The prestress was modulated using graded concentrations of contracting (histamine) or relaxing (isoproterenol) agonists and by disrupting MTs by colchicine. It was found that G increased in proportion with the prestress and that compression of MTs balanced a significant, but a relatively small fraction of the prestress. Taken together, these results do not disprove other models of cell deformability, nor they prove tensegrity. However, they do support a priori predictions of tensegrity. As such, it may not be necessary to invoke more complex mechanisms to explain these central features of cell deformability.
Characterization of cytoskeleton mechanical properties and 3D‐actin structure in twisted adherent epithelial cells
Authors: Fodil Redouane , Laurent Valérie , Planus Emmanuelle , Isabey Daniel
Published: November 2024

Evaluation of the cytoskeleton mechanical properties requires specific micromanipulation techniques such as the magnetic twisting cytometry technique, in which microbeads are specifically linked to the cytoskeleton via transmembrane receptors. The aim of the study was to assess the structural relationship between the bead and the cytoskeleton structure. The spatial arrangement of the CSK network was therefore studied in fixed cells probed by beads and stained for F‐actin by rhodamined phalloïdine. The spatial character of the actin CSK network, both in the bead neighborhood and at the cell scale, could then be studied for various degrees of fluorescent intensity from 3D‐images of the actin structure, reconstructed from z‐stack views obtained by confocal microscopy. Results show the feasibility of the staining/reconstruction technique which allows to reveal the three‐dimensional organization of the cytoskeleton structure including an internal cytosolic structure with a high fluorescent F‐actin intensity, and a sub‐membranous cortical structure with a low fluorescent F‐actin intensity.
Modeling of the detachment of a molecule from a surface: Illustration of the “Bell–Evans effect”
Authors: Hemmerlé J. , Picart C. , Gergely C. , Schaaf P. , Stoltz J.‐F. , Voegel J.‐C. , Senger B.
Published: November 2024

This article deals with the modeling of the detachment of a molecule initially adsorbed on a surface and submitted to an external force whose strength increases with time. By means of an atomic force microscope (AFM), it is possible to measure the force when the molecule separates from the substrate. However, it is known that this force depends to a large extend on the rate at which the pulling force is applied (“Bell–Evans effect”). Two models are described to illustrate this behavior. First, a random walk approach is suggested to reveal the fundamental principle of the escape over a time‐dependent energy barrier. Second, a multi bead‐and‐spring model is proposed to mimic the AFM experiment and numerical simulations, based on Brownian dynamics, are performed.
Role of mechanics in vascular tissue engineering
Authors: Nerem Robert M.
Published: November 2024

There is a clinical need for the tissue engineering of a small diameter blood vessel substitute. Ideally such a vascular substitute should possess the functional attributes of the native vessel which it will replace. This means not only having the appropriate mechanical properties, but also being non‐thrombogenic and exhibiting vasoactivity. In each of these there is in some way a role of mechanics. For thrombogenicity, an “endothelial‐like” lining is required, one which is responsive to its mechanical environment in a manner similar to that of the normal vascular endothelium. If vasoactivity is exhibited, then this lining must also serve as a signal transduction interface, communicating with the underlying smooth muscle cells which themselves must be of a contractile phenotype if they are to carry out the biomechanical function resulting in contraction and dilation. Having appropriate mechanical properties means not only exhibiting sufficient strength, but also a viscoelasticity which allows for a compliance that matches that of the vascular system into which the vascular substitute is to be placed. Finally, once implanted the biological responses which will occur at least in part are regulated by biomechanical factors. Thus, the proper incorporation of biomechanics into the design of a vascular substitute is critical to achieving success.
The role of tenascin‐C in adaptation of tendons to compressive loading
Authors: Martin J.A. , Mehr D. , Pardubsky P.D. , Buckwalter J.A.
Published: November 2024

Although most tendon regions are subjected primarily to high tensile loads, selected regions, primarily those that directly contact bones that change the direction of the tendon, must withstand high compressive loads as well. Compressed tendon regions differ from regions subjected to primarily tensile loads: they have a fibrocartilaginous structure with spherical cells surrounded by a matrix containing aggrecan and collagen types I and II, in contrast regions not exposed to compression have a fibrous structure with spindle shaped fibroblasts surrounded by a matrix of dense, longitudinally oriented type I collagen fibrils. The spherical shape of cells in fibrocartilagenous regions indicates these cells are more loosely attached to the matrix than their spindle‐shaped counterparts in fibrous regions, a feature that may help to minimize cell deformation during tendon compression. We hypothesized that expression of tenascin‐C, an anti‐adhesive protein, is part of the adaptation of tendon cells to compression that helps establish and maintain fibrocartilaginous regions. To test this hypothesis we compared tenascin‐C content and expression in compressed (distal) versus uncompressed (proximal) segments of bovine flexor tendons. Immunohistochemistry and immunoblot analyses showed that tenascin‐C content was increased in the distal tendon where it co‐distributed with type II collagen and aggrecan. Tendon cells from the distal segments expressed more tenascin‐C than did cells from the proximal segments for up to four days in cell culture, indicating that increased tenascin‐C expression is a relatively stable feature of the distal cells. These observations support the hypothesis that tenascin‐C expression is a cellular adaptation to compression that helps establish and maintain fibrocartilagenous regions of tendons.
Elliptic delamination as an early stage in atherosclerotic plaque evolution: Fluid mechanical aspects
Authors: Richardson Peter D.
Published: November 2024

Relatively little attention has been given to vessel wall mechanics in interaction with the pulsatile fluid motion of blood in the epicardial coronary arteries which are prone to atherosclerotic plaque development. Theories for lipid transport by convective effects, while appealing in many ways, do not serve to explain the predominantly bounded, elliptic profiles of atherosclerotic plaques when examined en face at gross autopsy. This paper outlines how structural–mechanical concepts relating to plaque shapes (starting from the shapes available even with isometric shell peeling to create the cavities typical of early plaques) can be combined with understanding of the blood pressure distribution which develops in the vicinity of a predominantly T‐junction in a blood vessel to modulate and interact in shape formation by cyclic, local flexure. This provides a foundation for a rational hypothesis to be tested in vivo with bi‐plane angiography and vessel wall imaging, e.g., intravascular ultrasound, to better assess the roles of solid and fluid mechanics in the localization of plaques.
The influence of humidity on the viscoelastic behaviour of human hair
Authors: Zuidema P. , Govaert L.E. , Baaijens F.P.T. , Ackermans P.A.J. , Asvadi S.
Published: November 2024

The possibility of curling hair is attributed to the fact that the mechanical properties of hair fibres depend on time, temperature and humidity. In this study the dependence of the viscoelastic behaviour of human hair fibres on humidity is characterised in a bending deformation. An experimental set‐up was used to perform bending relaxation measurements at different humidities. The relaxation data were fitted using a so‐called “stretched exponential equation”. The humidity dependence was incorporated by applying time–humidity superposition. Also, the influence of humidity on the initial E‐modulus was found. The influence of humidity on the behaviour of human hair fibres could be modelled by using a general characterisation of the behaviour of human hair fibres.

The general characterisation is used to predict the recovery in a human hair fibre after curling. The predicted recovery appeared to agree reasonably well with experimentally determined values.
Required test duration for group comparisons in ligament viscoelasticity: A statistical approach
Authors: Manley Eugene , Provenzano Paolo P. , Heisey Dennis , Lakes Roderic , Vanderby Ray
Published: November 2024

The goal of this study was to determine the duration of time that ligaments from a study group need to be loaded in order to adequately determine their collective viscoelastic behavior. Rat ligaments were subjected either to creep or stress relaxation for 1,000 s or stress relaxation for 10,000 s to compare estimates of viscoelastic behavior for different test durations. Stresses versus time (relaxation) or strains versus time (creep) were fit with power law models (tβ where β is the rate of creep or relaxation on a log–log scale). Time intervals were separated by logarithmic decade and analyzed using a Random Coefficients approach to compute residual specimen error as a function of the number of decades of data analyzed. Standard Regression was also used for comparison. Results show that by testing for ≤100 s (i.e. two logarithmic decades of time) offers 1% less accuracy than testing for 1,000 seconds (i.e. three decades) when estimating the viscoelastic behavior of a specimen. These 100 s power law estimates are far more accurate than the between specimen dispersion of viscoelastic properties. Hence, a better way to compare viscoelastic behavior between study groups is to test more specimens for shorter durations. This reduces experimental time per sample and therefore increases efficiency.