Biorheology - Volume 40, issue 1-3

Authors: Mattart, Mélanie | Mazzolai, Lucia | Chambaz, Céline | Hayoz, Daniel | Brunner, Hans R. | Silacci, Paolo

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 289-297, 2003

Authors: Botchwey, Edward A. | Pollack, Solomon R. | El‐Amin, Saadiq | Levine, Elliot M. | Tuan, Rocky S. | Laurencin, Cato T.

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 299-306, 2003

Authors: Nakayama, Koichi | Obara, Kazuo | Tanabe, Yoshiyuki | Saito, Maki | Ishikawa, Tomohisa | Nishizawa, Shigeru

Article Type: Research Article

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. Show more

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

Authors: Ruimerman, Ronald | van Rietbergen, Bert | Hilbers, Peter | Huiskes, Rik

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 315-320, 2003

Authors: Martin, J.A. | Mehr, D. | Pardubsky, P.D. | Buckwalter, J.A.

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 321-329, 2003

Authors: Démarteau, O. | Jakob, M. | Schäfer, D. | Heberer, M. | Martin, I.

Article Type: Research Article

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). Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 331-336, 2003

Authors: Berry, C.C. | Cacou, C. | Lee, D.A. | Bader, D.L. | Shelton, J.C.

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 337-345, 2003

Authors: Petrov, Nikola | Pollack, Solomon R.

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 347-353, 2003

Authors: Chotard‐Ghodsnia, R. | Drochon, A. | Faucheux, N. | Nagel, M.‐D. | Grebe, R.

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 355-360, 2003

Authors: Screen, H.R.C. | Lee, D.A. | Bader, D.L. | Shelton, J.C.

Article Type: Research Article

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. Show more

Citation: Biorheology, vol. 40, no. 1-3, pp. 361-368, 2003