Biorheology - Volume 46, issue 6

Authors: Amos, Jennifer R. | Li, Shigeng | Yost, Michael | Phloen, Harry | Potts, Jay D.

Article Type: Research Article

Abstract: In this work, we studied the effects of tensile strain on limb bud mesenchymal cells (MSC) cultured on a collagen type I tubular scaffold. A novel bioreactor was designed to culture the cells while subjecting the tubular scaffold to tensile stress and strain. Control samples included unseeded and MSC-seeded tubes cultured for 2 weeks under unloaded, no-strain conditions, and unseeded tubes subjected to prolonged tensile stress and strain. Mechanical properties of tube specimens were measured under oscillatory compressive stress. Following mechanical testing, scaffolds were fixed for immunohistochemistry or frozen for mRNA extraction. The storage modulii of both seeded/unstrained and seeded/strained …tubes were significantly less than that of unseeded tubes, suggesting that MSC disrupted the structure and elasticity of the tubes' collagen type I. At a frequency of 1.0 Hz, the loss tangent of seeded/strained tubes was more than 2.5 times greater than that of seeded/unstrained tubes, and almost 6 times greater than that of unseeded tubes. Confocal microscopy and qRT-PCR results demonstrated that collagen type II and aggrecan expression was upregulated in the seeded/strained tubes. The images also show, for the first time, that culture under tensile strain induces MSC to remodel the collagen type I tube with collagen type II and aggrecan expression into fibrils dispersed throughout the matrix. The seeded/unstrained tubes manifested less collagen type II with a more random expression pattern. Compared to seeded/unstrained tubes, qRT-PCR for collagen type II in the seeded/strained tubes showed a 4-fold increase in the message for collagen type II and a 13-fold increase in the message for aggrecan. These results demonstrate that MSC cultured for at least some period under tensile strain are able to remodel collagen type I scaffolds to produce a more viscous construct having many of the mechanical and biological features of engineered cartilage. Show more

Keywords: Fibrillar collagen, limb bud, mesenchyme, aggrecan, cartilage mechanical properties

DOI: 10.3233/BIR-2009-0553

Citation: Biorheology, vol. 46, no. 6, pp. 439-450, 2009

Authors: Natoli, Roman M. | Athanasiou, Kyriacos A.

Article Type: Review Article

Abstract: This review discusses a framework for studying injurious loading of articular cartilage, which can lead to post-traumatic osteoarthritis. The framework separates the mechanical from the biological response of the tissue to injury. The mechanical response is governed by the tissue's biomechanical behavior and sets off mechano-transductive pathways. These pathways then determine the biological response. The mechanical response of cartilage to injury has been studied by analytical and computational models of injurious loading, joint contact, and surface fissuring. These models have identified shear and tensile stresses as important parameters governing articular cartilage failure in response to mechanical injury. Further, measurement of …cartilage's material properties during impact loading has shown that the tissue is significantly stiffer than predicted from quasi-static testing. In terms of the biological response, cell death and sulfated glycosaminoglycan (sGAG) loss from the tissue are early degradative changes that lead to decreased tissue function. These biological sequelae have also been the subject of targeted intervention strategies post-injury. Some success has been found for decreasing cell death and sGAG loss using various bioactive agents. The framework and treatments reviewed here may be useful starting points in the study of mechanical injury to other tissues. Show more

Keywords: Mechanobiology, biomechanics, mechanotransduction, osteoarthritis, cell death, glycosaminoglycan

DOI: 10.3233/BIR-2009-0554

Citation: Biorheology, vol. 46, no. 6, pp. 451-485, 2009

Authors: Kaliviotis, Efstathios | Yianneskis, Michael

Article Type: Research Article

Abstract: Existing time-dependent blood viscosity models that involve aggregation dynamics are mainly based on structural variables and/or viscoelastic models in order to describe the bulk mechanical properties of the fluid, but the implications of important characteristics of blood microstructure, such as the time- and flow-dependent characteristics of the red blood cell network developed due to aggregation at low shear rates, have not been thoroughly investigated. In this paper a time-dependent blood viscosity model is developed based on an energy-rate model previously proposed (Skalak et al., Biophys. J. 35 (1977), 771–781), which describes the total work needed to overcome the various forces …developed between aggregated cells, including the adhesive, elastic and dissipative forces. Novel formulations of the forces acting on the fluid are developed and implemented in a volume-averaged version of the energy-rate model. The calculation of the viscosity is based on the relationship between the rate of energy changes and shear stress per unit volume of the fluid. The results show that network characteristics may significantly influence the viscosity blood at low shear rates and exhibit good agreement with experimental observations. Show more

Keywords: RBC aggregation, inter-cellular forces, network formation, energy balance

DOI: 10.3233/BIR-2009-0555

Citation: Biorheology, vol. 46, no. 6, pp. 487-508, 2009

Authors: Karšaj, I. | Humphrey, J.D.

Article Type: Research Article

Abstract: Quantifying mechanical properties of blood clots is fundamental to understanding many aspects of cardiovascular disease and its treatment. Nevertheless, there has been little attention to quantifying the evolving composition, structure and properties when a clot transforms from an initial fibrin-based mesh to a predominantly collagenous mass. Although more data are needed to formulate a complete mathematical model of the evolution of clot properties, we propose a general constrained mixture model based on diverse data available from in vitro tests on fibrinogenesis, the stiffness of fibrin gels, and fibrinolysis as well as histological and mechanical data from clots retrieved from patients …at surgery or autopsy. In particular, albeit resulting from complex kinetics involving many clotting factors, we show that the rapid (minutes) in vitro production of fibrin from fibrinogen can be modeled well by an Avrami-type relation and similarly that the fast (tens of minutes) in vitro degradation of fibrin in response to different concentrations of plasmin can be captured via a single “master function” parameterized by appropriate half-times that can be inferred from laboratory or clinical data. Accounting simultaneously for the production and removal of fibrin as well as chemo-mechano-stimulated production of fibrillar collagens yields predictions of changing mass fractions and bulk mechanical properties that correspond well to experimentally available data. Constrained mixture models thus hold considerable promise for modeling the biomechanics of clot evolution and can guide the design and interpretation of needed experiments and stress analyses. Show more

Keywords: Coagulation, blood clot, fibrin gel, collagen organization, mechanical stress

DOI: 10.3233/BIR-2009-0556

Citation: Biorheology, vol. 46, no. 6, pp. 509-527, 2009

Authors: Shepherd, Robert D. | Kos, Stephanie M. | Rinker, Kristina D.

Article Type: Research Article

Abstract: Fluid dynamics strongly influences endothelial cell function, and participates in the localization of atherosclerotic plaques at blood vessel branches. We investigated the hypothesis that wild-type human aortic endothelial cells (HAEC) exposed to prolonged pulsatile flow stimulation have levels of phosphorylated mitogen-activated protein kinases (MAPK) that are significantly greater than those observed in statically grown cultures. HAEC were exposed to pulsatile laminar shear stress in a parallel-plate flow chamber and analyzed for levels of phosphorylated ERK, JNK and p38 at 1, 10 and 20 h. While some MAPK exhibited alternating patterns of phosphorylation, others were characterized by steady increases or unchanged …profiles until the terminal (20 h) time point. However, at 20 h, each MAPK demonstrated an increase in phosphorylation versus statically cultivated cells. Further, 20 h cultures from 10 dyn/cm2 pulsatile shear stress had higher levels of phosphorylation for each MAPK than those from 2 dyn/cm2 . The finding that MAPK species can be phosphorylated in response to a prolonged pulsatile shear stress in both a time and magnitude dependent manner is an interesting result that may help to explain how the differential behaviors observed between cells from different flow environments can be generated and maintained. Show more

Keywords: Fluid flow, signal transduction, mitogen activated protein kinases, mechanotransduction

DOI: 10.3233/BIR-2009-0557

Citation: Biorheology, vol. 46, no. 6, pp. 529-538, 2009

Article Type: Other

Citation: Biorheology, vol. 46, no. 6, pp. 539-543, 2009