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Biorheology is an international interdisciplinary journal that publishes research on the deformation and flow properties of biological systems or materials. It is the aim of the editors and publishers of
Biorheology to bring together contributions from those working in various fields of biorheological research from all over the world. A diverse editorial board with broad international representation provides guidance and expertise in wide-ranging applications of rheological methods to biological systems and materials.
The aim of biorheological research is to determine and characterize the dynamics of physiological processes at all levels of organization. Manuscripts should report original theoretical and/or experimental research promoting the scientific and technological advances in a broad field that ranges from the rheology of macromolecules and macromolecular arrays to cell, tissue and organ rheology. In all these areas, the interrelationships of rheological properties of the systems or materials investigated and their structural and functional aspects are stressed.
The scope of papers solicited by
Biorheology extends to systems at different levels of organization that have never been studied before, or, if studied previously, have either never been analyzed in terms of their rheological properties or have not been studied from the point of view of the rheological matching between their structural and functional properties. This biorheological approach applies in particular to molecular studies where changes of physical properties and conformation are investigated without reference to how the process actually takes place, how the forces generated are matched to the properties of the structures and environment concerned, proper time scales, or what structures or strength of structures are required.
Biorheology invites papers in which such 'molecular biorheological' aspects, whether in animal or plant systems, are examined and discussed. While we emphasize the biorheology of physiological function in organs and systems, the biorheology of disease is of equal interest. Biorheological analyses of pathological processes and their clinical implications are encouraged, including basic clinical research on hemodynamics and hemorheology.
In keeping with the rapidly developing fields of mechanobiology and regenerative medicine,
Biorheology aims to include studies of the rheological aspects of these fields by focusing on the dynamics of mechanical stress formation and the response of biological materials at the molecular and cellular level resulting from fluid-solid interactions. With increasing focus on new applications of nanotechnology to biological systems, rheological studies of the behavior of biological materials in therapeutic or diagnostic medical devices operating at the micro and nano scales are most welcome.
Abstract: Both plaque‐free and plaque‐prone hemodynamic environments induce an increase in the oxidative state of endothelial cells (ECs), whereas differential gene expression regulation was described in cells exposed to these conditions. In order to investigate the role of the increased oxidative state in flow‐regulation of gene expression, we first exposed EC to non‐pulsed unidirectional shear stress. These conditions only slightly increases ECs oxidative state and endothelin‐1 (ET‐1) mRNA expression, whereas endothelial nitric oxide synthase (NOS III) mRNA level were significantly up‐regulated. On the contrary, both ET‐1 and NOS III gene expression were significantly induced in EC exposed to pulsed‐unidirectional flow (plaque‐free).…Only ET‐1 gene expression was up‐regulated by oscillatory flow (plaque‐prone). Moreover, use of an antioxidant only partially inhibited NOS III gene up‐regulation by unidirectional flow, whereas it completely abrogated ET‐1 gene up‐regulation by unidirectional and oscillatory flows. Thus suggesting that mechanical forces regulate gene expression in ECs both via oxidative stress‐dependent and ‐independent mechanisms.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 289-297, 2003
Abstract: In a previous study, we showed that the combination of appropriately designed three‐dimensional (3D) microcarrier scaffolds and fluid flow through and around the scaffolds during high aspect ratio vessel (HARV) rotation enhances the elaboration of mineralized bone matrix by osteoblast‐like cells. In this study, we describe the ongoing characterization of our 3D culture system, including the investigation of interior fluid flow within the scaffolds and early stage integrin expression during hydrodynamic culture. Using theoretical and experimental methods, we have estimated that cells cultured on the interior of microcarrier scaffolds experience an interior nutrient flow velocity between 1×10−3 and 1×10−2…cm/s and maximum shear stress of 0.03 N/m2 . Under these conditions, osteoblast‐like cells grew extensively in the interior regions of the scaffold and retained their osteoblastic phenotype as measured by alkaline phosphatase. In addition, flow cytometric analysis of the overall cell population showed that cells constitutively expressed integrin α3 β1 during 3D hydrodynamic culture.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 299-306, 2003
Abstract: Blood vessels are always subjected to hemodynamic stresses including blood pressure and blood flow. The cerebral artery is particularly sensitive to hemodynamic stresses such as pressure and stretch, and shows contractions that are myogenic in nature; i.e., the mechanical response is generated by the vascular smooth muscle itself. The artery constricts in response to an increase in intraluminal pressure, and dilates in response to a decrease in the intraluminal pressure. We provide herein some insights into the mechanotransduction of vascular tissue; i.e., we discuss how the tissue is receptive to mechanical force and how the latter induces the specific signals…leading to myogenic contraction in terms of mechanosensor action and subsequent intracellular signaling. The interactive role of tyrosine kinase, protein kinase C, and Rho/Rho‐kinase systems in the mechanotransduction process is discussed, which systems also seem to play an important role in the development of experimental cerebral vasospasm. The study of the mechanotransduction in vascular tissue may aid in clarifying the mechanisms underlying vasospastic episodes and pathologic remodeling in cardiovascular diseases, and may potentially have therapeutic consequences.
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Keywords: Mechanotransduction, stretch‐induced contraction, cerebrovascular contraction, cerebral vasospasm, tyrosine kinase, protein kinase C isoforms, Rho/Rho‐kinase, myosin light‐chain phosphorylation, tyrosine phosphorylation
Citation: Biorheology,
vol. 40, no. 1-3, pp. 307-314, 2003
Abstract: Mechanical loading of trabecular bone affects the bone architecture. Bone mass is correlated to the magnitude of the external load and trabeculae are aligned to the loading direction. Physical exercise increases bone mass while disuse or microgravity decreases it. In previous work we have presented a mathematical model of bone metabolism that could explain the emergence, maintenance and adaptation of trabecular bone under influence of the load imposed, using a 2‐dimensional computer model (Huiskes et al., Nature 404 (2000), 704–706). This model was based on hypothetical mathematical descriptions of bone formation by osteoblastic cells, and resorption by osteoclastic cells, both…as governed by mechanical stimuli. In order to quantitatively compare the behavior of the proposed regulation mechanism to real trabecular bone metabolism we present a 3‐dimensional computer simulation model. The first 3‐dimensional simulation results show that the regulatory rules proposed earlier mimic trabecular bone metabolism in a robust way.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 315-320, 2003
Abstract: 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.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 321-329, 2003
Abstract: A bioreactor has been developed to apply different regimes of physical stimulation to tissue specimens under highly controlled conditions. The computer‐controlled device exposes specimens to compressive deformation at various strains and frequencies, measures the load applied to each sample and allows simultaneous medium stirring at different velocities. Validation tests confirmed the accuracy of the system in (i) its displacement (errors averaged 0.072±0.051 μm), and in (ii) setting the contact with the samples utilizing micrometer screws coupled to plungers (errors averaged 1.74±0.36% for samples of 1.60–3.18 mm thickness), thus ensuring accurate compressive deformation. The developed bioreactor, which represents an advance in…the technology for physical stimulation of tissue specimens, is currently used to apply compressive deformation and hydrodynamic forces to human chondrocytes cultured in biodegradable polymer scaffolds, with the goals of (i) engineering functional grafts for the repair of cartilage defects (ii).
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 331-336, 2003
Abstract: Fibroblasts within tissues are exposed to a dynamic mechanical environment, which influences the structural integrity of both healthy and healing soft tissues. Various systems have been proposed to subject such cells to mechanical stimulation in culture. However the diverse nature of the studies, in terms of the strain profiles and the cell types, makes direct comparisons almost impossible. The present study addresses this issue by examining the metabolic response of two cell types subjected to three well defined strain profiles. A young fibroblast cell population, represented by HuFFs, showed both greater cell proliferation and collagen production than adult dermal…fibroblasts under unstrained conditions. The three strain profiles produced differing effects on both cell types. Uniaxial strains enhanced [3 H]‐thymidine incorporation for both cell types, whilst biaxial strains either inhibited or had no effect on its incorporation. In contrast, [3 H]‐proline incorporation was inhibited under biaxial and uniaxial strains for the adult fibroblasts, whilst the HuFF cells showed a small increase in proline incorporation under non‐uniform and uniaxial strains.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 337-345, 2003
Abstract: Marker migration experiments suggest that cyclic mechanical loading of cortical bone in vivo increases marker penetration into bone. Is this a result of stress induced fluid flow or of stress stimulation of active transport processes? Active lacunar–canalicular transport of nutrients was suggested by Ham in 1979 on the basis of the presence of actin filaments in osteocyte processes and their suspected role in cell motility. In addition, Tanaka in 1984 observed active transport of microperoxidase in bone and Tanaka‐Kamioka et al. in 1998 observed experimentally that osteocyte processes are able to actively change their form. In this study we…performed parametric and comparative analyses of the transport efficiencies of diffusion and stress generated fluid flow of (glucose) nutrients in lacunar–canalicular systems in cortical bone. The result obtained is that neither diffusion nor stress induced fluid flow is capable of sustaining osteocyte viability. It is possible that cyclic stress stimulates an active nutrient transport mechanism to supplement stress flows.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 347-353, 2003
Abstract: Biomaterials used in some biomedical devices are exposed to flow of physiological fluids. The flow‐induced forces may influence the morphological and the biochemical responses of adhering cells. The objective of this work is to examine the capacity of a mechanical stress to cause changes in cell/substratum and cell/cell interactions via the second messenger cAMP pathway (cyclic Adenosine Monophosphate). Cyclic AMP is known to modulate cell shape, cell adhesion and intercellular communication in static conditions. A specially designed flow chamber was used to analyze the responses of mouse 3T3 fibroblasts spread on biocompatible substrata and submitted to controlled shear stresses. A…1.1‐Pa shear stress induced: cell rounding, disruption of vitronectin receptors clusters and clustering of connexins 43 at cell–cell apposition points. These cell responses were cAMP‐dependent. These investigations should help provide a better understanding of the early biochemical events triggered by mechanical forces.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 355-360, 2003
Abstract: Tenocytes detect mechanical stimuli in vivo, and respond through mechanotransduction pathways to initiate matrix remodelling in tendons. Due to the crimped nature of tendon fascicles, the strain field throughout is non‐homogeneous. The present study has developed a means to quantify the local strain fields within a fascicle by monitoring the relative movement and deformation of fluorescently labelled tenocyte nuclei. A stage mounted test rig was designed to apply tensile strain to fascicles. Rat tail and bovine extensor tendons were harvested for analysis, and the cell nuclei stained and visualised using an inverted confocal microscope. As the fascicles were subjected to…gross strains of up to 5%, the movement of selected tenocyte nuclei were recorded. Results from a series of cell nuclei from both tendon sources revealed that local strains were significantly less than the applied strain. The nuclei length to width ratio, an indicator of cell deformation, also increased with applied strain, most significantly between 2 and 3% applied strain.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 361-368, 2003
Abstract: The aim of this study was to determine the comparative three‐dimensional mechanical properties of healthy and atherosclerotic muscular human arteries. Using a previously developed experimental system, in vitro inflation tests were performed on twelve segments of arteries, in static conditions. Two different initial states were used to carry the mechanical study through (large deformation, thick‐walled). Main significant differences between healthy and atherosclerotic tested segments are observed for axial traction force whatever the initial state and radial and circumferencial strains referenced to longitudinally pre‐stretched state. We showed that strain energy allows to differentiate between both types of arteries only when absolute…values of transversal components were considered. Differential values of energy were not discriminating. Our results also show the potential interest of studying arteries in vivo at low transmural pressure.
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Keywords: Wall rheology, inflation tests, unloaded state, human artery, atherosclerosis
Citation: Biorheology,
vol. 40, no. 1-3, pp. 369-376, 2003
Abstract: This study aimed at the determination of the influence of exercise on the levels of a number of bone morphogenic enzymes in subchondral bone and at the comparison of these data with other (subchondral) bone‐related parameters that have been investigated in the same experimental population. Forty‐three foals were reared until weaning at 5 months of age under similar conditions, except for the type and amount of exercise. Fifteen foals remained at pasture (Pasture group and also control group), 14 foals were kept in box stalls (Box group) and 14 foals were kept in the same box stalls but were…subjected daily to an increasing number of gallop sprints (Training group). After weaning 8 foals from each group were euthanised. All remaining 19 animals were housed together in a loose box with access to a small paddock to study a possible reversibility of exercise‐induced effects. Post mortem subchondral bone samples were collected from the femoropatellar joint and analysed for the bone morphogenic enzymes alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and lysyl oxidase (LO). Data were compared to calcium content, numbers of collagen cross‐links, bone mineral density (BMD) and cross‐sectional area (CSA) collected in other bone‐related studies in the same group of experimental animals. At 5 months of age, ALP levels were significantly lower and TRAP levels higher in both the Box and the Training group, making the ALP : TRAP ratio reversed in relation to the Pasture group. LO levels were lower in the Box group only. The ALP and TRAP data corresponded with changes in CSA, but not with calcium and BMD, the levels of which were the same in the Training and Pasture groups. The LO levels corresponded nicely with hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross‐links. At 11 months of age ALP and TRAP levels had reached similar levels in most groups, normalising the ALP : TRAP ratio. TRAP levels in the former Training group lagged somewhat behind. LO levels were still significantly lower in the former Box rest group. It is concluded that the overall increase in bone mass (characterised by the change in CSA) is apparently related to continuous, evenly distributed exercise as in the Pasture group (natural situation). This process seems to be related with ALP and TRAP levels and their ratio. For normal cross‐link levels and BMD, short heavy bouts of exercise superimposed on a basic rest regimen seem sufficient. However, both data from this study and from earlier studies suggest that this latter exercise regimen might have a long‐term deleterious effect.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 377-382, 2003
Abstract: Skeletal muscle tissue is highly susceptible to sustained compressive straining, eventually leading to tissue breakdown in the form of pressure sores. This breakdown begins at the cellular level and is believed to be triggered by sustained cell deformation. To study the relationship between compressive strain‐induced muscle cell deformation and damage, and to investigate the role of cell–cell interactions, cell–matrix interactions and tissue geometry in this process, in vitro models of single cells, monolayers and 3D tissue analogs under compression are being developed. Compression is induced using specially designed loading devices, while cell deformation is visualised with confocal microscopy. Cell damage…is assessed from viability tests, vital microscopy and histological or biochemical analyses. Preliminary results from a 3D cell seeded agarose model indicate that cell deformation is indeed an important trigger for cell damage; sustained compression of the model at 20% strain results in a significant increase in cell damage with time of compression, whereas damage in unstrained controls remains constant over time.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 383-388, 2003
Abstract: Objective: To further establish a definite basic of the application value of sodium ferulate (SF) for prevention and cure of acute coronary heart disease, we examined the effects of SF on LDL oxidation and lipid accumulation in rabbit aortic smooth muscle cells induced by modified‐LDL. Methods: LDL oxidation was carried out in the presence and absence of SF. Cultured rabbit aortic smooth muscle cells were used as the model. To investigate the effects of SF on intracellular lipid accumulation, cells were incubated with Ox‐LDL and SF. The lipid content (cholesterol and triglycerides) of the cells were determined. Results:…Intracellular cholesterol and triglycerides were significantly increased in cell‐modified LDL group. The enhancements of above indexes were decreased after addition of SF (200 μg/ml). On the other hand, incubation of LDL with SF resulted in a significant decrease in TBARS activity and electrophoretic mobility. Conclusion: The results indicated that SF assume significance both in the protection of LDL against oxidation and inhibition of cell‐modified LDL effects on intracellular lipid with the potential to prevent cell foamation.
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Keywords: Oxidized low density lipoproteins, foam cells, atherosclerosis, sodium ferulate
Citation: Biorheology,
vol. 40, no. 1-3, pp. 389-394, 2003
Abstract: The aim of this article was to examine the protective effect of Chinese traditional medicine angelica on human umbilical vein endothelial cells (HUVECs, ECV304 ) from injury induced by hyperlipidemic serum (HLS) and to study the underlying mechanism. Spectrophotometer and immunocytochemical methods were used to detect the content of nitric oxide (NO) in suspension and expression of intercellular adhesion molecule‐1 (ICAM‐1), transforming growth factor β1 (TGFβ1 ), basic fibroblast growth factor (bFGF) on the cell surface, respectively. After incubated with 50 μl/ml HLS for 24 hours, expression of ICAM‐1 and bFGF in ECs was significantly increased, while expression of…TGFβ1 and the release of NO from ECs were significantly decreased. All these effect of HLS on ECs can be reversed by angelica significantly. The above effect of angelica may be related to its anti‐atherosclerotic action. Our findings provided experimental basement for the clinical application of angelica to prevent the development of atherosclerosis.
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Keywords: Angelica, vascular endothelial cell, ICAM‐1, TGF$\beta_{1}$, bFGF, NO, atherosclerosis
Citation: Biorheology,
vol. 40, no. 1-3, pp. 395-399, 2003
Abstract: In this study, we examine the response of cultured hippocampal neurons to mechanical stretch. To measure the immediate response, we measured the response of a calcium sensitive fluorescent dye (Fura‐2AM) prior to and for five minutes following stretch. In separate experiments, we measured the viability of the cells using propidium iodide labeling at 24 hours following a single stretch. Results show that cytosolic calcium increases immediately following stretch to levels much higher than those associated with maximal chemical agonist (NMDA) stimulation. Moreover, the calcium response data indicate a loss in calcium regulation in the neurons at the most severe level…of stretch. Finally, at the highest levels of stretch, the cell survivability decreases at 24 hrs following the stretch injury. These data show the association between loss in calcium regulation and early signs of neuronal cell death.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 401-409, 2003
Abstract: The promising concept of cell transplantation and cardiac tissue engineering has been developed in the last few years and focused on strategies attempting to replace dysfunctional, necrotic, and/or apoptotic cardiomyocytes with new cells of mesodermal origin. Transplantation of autologous cells minimizes the risk of neoplasia and avoids immune rejection associated with allogenic or xenogenic cells and recent data hold enormous hopes for short term clinical practices. Tissue engineering represents another promising approach that makes possible the creation of new functional tissues to replace the lost or failing one. Three‐dimensional polymeric scaffolds provide the mechanical support for the candidate cells until…the formation of cardiac‐like tissue prior to surgical repair of the infarcted myocardium. For ultimate clinical applications, further investigations have to select the appropriate cell types, to determine the sufficient number of grafted cells and to provide the long term evaluation of these strategies in the global improvements of cardiac function (neoangiogenesis, synchronous contraction and extracellular matrix remodelling).
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Abstract: 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.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 417-421, 2003
Abstract: It has been extensively documented that changes in blood flow induce vascular remodeling and this phenomenon seems to be correlated to the shear forces imposed on the vessel wall by motion of blood. Wall shear stress, the tractive force that acts on the endothelium, has been shown to influence endothelial cell function. To study changes in wall shear stress that develop on the vessel wall upon changes of blood flow, we set up a technique that allows estimation of shear stress in the radial artery of patients on chronic hemodialysis therapy. The technique is based on color‐flow Doppler examination of…the radial artery before and after surgical creation of radiocephalic fistula for hemodialysis. Calculation of time function wall shear stress and blood flow rate in the radial artery is performed on the basis of arterial diameter, center‐line velocity waveform and blood viscosity, using a numerical method developed according to Womersley's theory for pulsatile flow in tubes. The results presented confirm that the model developed is suitable for calculation of the wall shear stress that develops in the radial artery of patients before and after surgical creation of an arteriovenous fistula for hemodialysis. This methodology was developed for characterization of wall shear stress in the radial artery but may be well applied to other vessels that can be examined by echo‐Doppler technique.
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Citation: Biorheology,
vol. 40, no. 1-3, pp. 423-430, 2003