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Shear stress protects against endothelial regulation of vascular smooth muscle cell migration in a co-culture system
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Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)
6638 Mo-Tu, no. 73 (P66) Large-eddy simulations of fluid-structure interactions in prosthetic heart valves A. Cristallo 1,2, E. Balaras 1, R. Verzicco 2, A. Yoganathan 3. 1Department ef Mechanical Engineering, University of Maryland, College Park, MD, USA, 2Dipartimento di Engegneria Meccanica e Gestionale, Politecnico di Bari, Bad, Italy, 3Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA The complex turbulent/transitional flow patterns induced by prosthetic heart valves have a significant impact on thromboembolic complications that remain a major concern after surgery. To illuminate the detailed dynamics of the flow in the vicinity of such valves we performed Direct Numerical Simulations (DNS) and Large-Eddy Simulations (LES) in a simplified configuration. In particular, the selected shape and size of the leaflets mimics the SJM Standard bi-leaflet valve, and is located in a straight pipe with rigid walls, which expands and then contracts to mimic the geometry of the aortic root. A physiologic waveform is imposed at the inflow plane upstream of the valve, with peak Reynolds number Re=6,500 (Re is based on the bulk velocity and diameter of the tube). The overall set-up resembles the one commonly used in in-vitro experiments. Both DNS and LES of the fluid-structure interaction problem were performed using a sharp-interface, embedded boundary formulation, where complex moving boundaries are tracked on a structured computational grid that does not follow the shape of the body. A strong coupling scheme was found to be necessary for the stability of the overall algorithm. Grids with up to approximately 10 million nodes were used to establish independency of the results from numerical resolution. The motion of the leaflets, which open at the beginning of the systole and close before the start of the diastole was found to be similar to what has been observed in experimental studies. Detailed phase-averaged statistics for the mean flow and Reynolds stresses will be shown. Emphasis will be given on the spatio-temporal evolution of organized vortical structures originating from the leaflets and the housing that are responsible for most of the production of turbulent stress in the downstream area.
Poster Presentations
14.10 Large Vessel Fluid Mechanics - Implants and Devices 5986 Mo-Tu, no. 75 (P66) Investigation of the fluid dynamical properties o f helical pipes from a mixing perspective A. Cookson, D. Doorly, S. Sherwin. Department of Aeronautics, Imperial College, London, UK Cardiovascular disease is responsible for the majority of deaths in developed countries, and of these most are associated with abnormalities in arterial blood flow. Atherogenesis often results in an arterial stenosis that is treated by the surgical insertion of a bypass graft. Unfortunately, over 50% of coronary artery bypass grafts fail within 10 years due to the development of neointimal hyperplasia. Computational studies suggest that the three-dimensional geometry of non-planar grafts introduces a physiologically more favourable flow environment (reduced shear extrema, lower particle residence times and increased mixing) [1], however preservation of this geometry post surgery is difficult. Caro et al. [2] have proposed that small amplitude helical tubes will achieve the same fluid dynamical properties as a non-planar graft, but with the benefit of mechanical robustness. A preliminary in-vivo study comparing the small amplitude helical pipes with cylindrical pipes for use as shunts found that after eight weeks the conventional technology was fully occluded, but completely clear for the helical shunt. This work aims to investigate the fluid dynamical properties of the flow through helical pipes, so that the mechanisms behind their success as bypass grafts and shunts can be understood. It is known qualitatively that there is substantial in-plane mixing in a helical pipe, due to the swirl induced by the geometry. Previous work on helical pipes has generally focused on the primitive variables such as velocity profiles, whereas this paper will examine the flow from a mixing perspective using entropic measures, Lyapunov exponents and particle residence times to quantify the degree of mixing, and then relate this to geometric parameters of the helix.
5067 Mo-Tu, no. 74 (P66) Non-invasive assessment of leaflet deformation in heart valve tissue engineering J. Kortsmit, M.C.M. Rutten, EP.T. Baaijens. Eindheven University ef Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands
References [1] Sherwin et al. The influence of out-of-plane geometry on the flow within a distal end-to-side anastomosis, ASME J. Biomech. 2000; 122. [2] Caro C.G., Cheshire N.J., Watkins N. Preliminary comparative study of small amplitude helical and conventional ePTFE arteriovenous shunts in pigs. J. R. Soc. Interface, 2005; 2.
Contemporary tissue engineered heart valves lack mechanical strength for implantation in the high-pressure aortic position [1]. Recent studies indicate enhancement of mechanical properties by applying cyclic diastolic pressure loads to the developing tissue in a bioreactor system [2]. Current bioreactors operate with a preset transvalvular pressure applied to the tissue. The induced deformations are unknown and can vary during culturing as a consequence of changing mechanical properties of the engineered construct. Real-time measurement and control of local tissue strains are desired to systematically study the effects of mechanical loading on tissue development and, consequently, to design an optimal conditioning protocol. In this study, a bioreactor system is developed which is able to measure and control deformation of the heart valve leaflets during conditioning. Deformation measurement is performed using flow sensors as non-invasive measurement method. The amount of fluid displaced by the deformed heart valve represents the volumetric deformation of the leaflets in a stented configuration. Consecutively, a finite element model [3] is employed to relate the measured volumetric deformation to local tissue strains in the belly and commissures of the leaflets. Validation is performed by loading a rubber membrane and measuring deformation by using an optical technique. In a tissue engineering experiment, the functionality of the measurement method is also demonstrated. Feedback regulation will be incorporated into the bioreactor system by which the pressure load acting on the valve can be adjusted to control local tissue strains in the valve leaflets. This system has a great potential for developing the optimal conditioning protocol for tissue engineering of heart valves.
14.11 Mechanobiology of Vascular Walls and Cells
References [1] Hoerstrup SP, et al. Circulation 2000; 102(19): 11144-49. [2] Mol A, et al. Annals of Biomed. Eng. 2005; 33(12): 1778-1788. [3] Driessen NJB, et al. J. Biomech. Eng. 2005; 127(2): 329-336.
5031 Mo-Tu, no. 76 (P66) Shear stress protects against endothelial regulation of vascular smooth muscle cell migration in a co-culture system Z.-L. Jiang, H.-Q. Wang, L.-X. Huang, M.-J. Qu, Z.-Q. Yan, B. Liu, B.-R. Shen. Institute of Mechanobiology & Medical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Vascular endothelial cells (ECs) are constantly exposed to blood flow-induced shear stress, which strongly influence the behaviors of neighboring vascular smooth muscle cells (VSMCs). VSMC migration is a key event in vascular wall remodeling. Current study will provide a new insight into how shear stress modulates VSMC migration in the presence of an intact endothelium. We assessed the difference of VSMC migration between VSMC/EC co-culture under static condition and in response to shear stress. With a parallel-plate co-culture flow chamber system and Transwell migration assays, we demonstrated that human ECs co-cultured with VSMCs under static condition induced VSMC migration, whereas laminar shear stress (l.5Pa, 15dynes/cm 2) applied to EC side for 12h significantly inhibited this process. The changes in VSMC migration is mainly dependent on the close interactions between ECs and VSMCs. Western blotting showed that there was a consistent correlation between the level of Akt phosphorylation and the efficacy of shear stress-mediated EC regulation VSMC migration. Wortmannin and Akti, significantly inhibited the EC-induced effect on VSMC Akt phosphrylation and migration. VSMC-EC close interaction is required for activation of PI3K/Akt, which plays a key role in VSMC migration. These results indicate that shear stress modulates VSMC migration in an endothelium-dependent fashion, exerting an atheroprotective function on the vessel wall. This research was supported by grants from the National Natural Science Foundation of China, No.10132020, No. 30070197.
Journal o f Biomechanics 2006, Vol. 39 (Suppl 1)
6638 Mo-Tu, no. 73 (P66) Large-eddy simulations of fluid-structure interactions in prosthetic heart valves A. Cristallo 1,2, E. Balaras 1, R. Verzicco 2, A. Yoganathan 3. 1Department ef Mechanical Engineering, University of Maryland, College Park, MD, USA, 2Dipartimento di Engegneria Meccanica e Gestionale, Politecnico di Bari, Bad, Italy, 3Wallace H. Coulter School of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA The complex turbulent/transitional flow patterns induced by prosthetic heart valves have a significant impact on thromboembolic complications that remain a major concern after surgery. To illuminate the detailed dynamics of the flow in the vicinity of such valves we performed Direct Numerical Simulations (DNS) and Large-Eddy Simulations (LES) in a simplified configuration. In particular, the selected shape and size of the leaflets mimics the SJM Standard bi-leaflet valve, and is located in a straight pipe with rigid walls, which expands and then contracts to mimic the geometry of the aortic root. A physiologic waveform is imposed at the inflow plane upstream of the valve, with peak Reynolds number Re=6,500 (Re is based on the bulk velocity and diameter of the tube). The overall set-up resembles the one commonly used in in-vitro experiments. Both DNS and LES of the fluid-structure interaction problem were performed using a sharp-interface, embedded boundary formulation, where complex moving boundaries are tracked on a structured computational grid that does not follow the shape of the body. A strong coupling scheme was found to be necessary for the stability of the overall algorithm. Grids with up to approximately 10 million nodes were used to establish independency of the results from numerical resolution. The motion of the leaflets, which open at the beginning of the systole and close before the start of the diastole was found to be similar to what has been observed in experimental studies. Detailed phase-averaged statistics for the mean flow and Reynolds stresses will be shown. Emphasis will be given on the spatio-temporal evolution of organized vortical structures originating from the leaflets and the housing that are responsible for most of the production of turbulent stress in the downstream area.
Poster Presentations
14.10 Large Vessel Fluid Mechanics - Implants and Devices 5986 Mo-Tu, no. 75 (P66) Investigation of the fluid dynamical properties o f helical pipes from a mixing perspective A. Cookson, D. Doorly, S. Sherwin. Department of Aeronautics, Imperial College, London, UK Cardiovascular disease is responsible for the majority of deaths in developed countries, and of these most are associated with abnormalities in arterial blood flow. Atherogenesis often results in an arterial stenosis that is treated by the surgical insertion of a bypass graft. Unfortunately, over 50% of coronary artery bypass grafts fail within 10 years due to the development of neointimal hyperplasia. Computational studies suggest that the three-dimensional geometry of non-planar grafts introduces a physiologically more favourable flow environment (reduced shear extrema, lower particle residence times and increased mixing) [1], however preservation of this geometry post surgery is difficult. Caro et al. [2] have proposed that small amplitude helical tubes will achieve the same fluid dynamical properties as a non-planar graft, but with the benefit of mechanical robustness. A preliminary in-vivo study comparing the small amplitude helical pipes with cylindrical pipes for use as shunts found that after eight weeks the conventional technology was fully occluded, but completely clear for the helical shunt. This work aims to investigate the fluid dynamical properties of the flow through helical pipes, so that the mechanisms behind their success as bypass grafts and shunts can be understood. It is known qualitatively that there is substantial in-plane mixing in a helical pipe, due to the swirl induced by the geometry. Previous work on helical pipes has generally focused on the primitive variables such as velocity profiles, whereas this paper will examine the flow from a mixing perspective using entropic measures, Lyapunov exponents and particle residence times to quantify the degree of mixing, and then relate this to geometric parameters of the helix.
5067 Mo-Tu, no. 74 (P66) Non-invasive assessment of leaflet deformation in heart valve tissue engineering J. Kortsmit, M.C.M. Rutten, EP.T. Baaijens. Eindheven University ef Technology, Department of Biomedical Engineering, Eindhoven, The Netherlands
References [1] Sherwin et al. The influence of out-of-plane geometry on the flow within a distal end-to-side anastomosis, ASME J. Biomech. 2000; 122. [2] Caro C.G., Cheshire N.J., Watkins N. Preliminary comparative study of small amplitude helical and conventional ePTFE arteriovenous shunts in pigs. J. R. Soc. Interface, 2005; 2.
Contemporary tissue engineered heart valves lack mechanical strength for implantation in the high-pressure aortic position [1]. Recent studies indicate enhancement of mechanical properties by applying cyclic diastolic pressure loads to the developing tissue in a bioreactor system [2]. Current bioreactors operate with a preset transvalvular pressure applied to the tissue. The induced deformations are unknown and can vary during culturing as a consequence of changing mechanical properties of the engineered construct. Real-time measurement and control of local tissue strains are desired to systematically study the effects of mechanical loading on tissue development and, consequently, to design an optimal conditioning protocol. In this study, a bioreactor system is developed which is able to measure and control deformation of the heart valve leaflets during conditioning. Deformation measurement is performed using flow sensors as non-invasive measurement method. The amount of fluid displaced by the deformed heart valve represents the volumetric deformation of the leaflets in a stented configuration. Consecutively, a finite element model [3] is employed to relate the measured volumetric deformation to local tissue strains in the belly and commissures of the leaflets. Validation is performed by loading a rubber membrane and measuring deformation by using an optical technique. In a tissue engineering experiment, the functionality of the measurement method is also demonstrated. Feedback regulation will be incorporated into the bioreactor system by which the pressure load acting on the valve can be adjusted to control local tissue strains in the valve leaflets. This system has a great potential for developing the optimal conditioning protocol for tissue engineering of heart valves.
14.11 Mechanobiology of Vascular Walls and Cells
References [1] Hoerstrup SP, et al. Circulation 2000; 102(19): 11144-49. [2] Mol A, et al. Annals of Biomed. Eng. 2005; 33(12): 1778-1788. [3] Driessen NJB, et al. J. Biomech. Eng. 2005; 127(2): 329-336.
5031 Mo-Tu, no. 76 (P66) Shear stress protects against endothelial regulation of vascular smooth muscle cell migration in a co-culture system Z.-L. Jiang, H.-Q. Wang, L.-X. Huang, M.-J. Qu, Z.-Q. Yan, B. Liu, B.-R. Shen. Institute of Mechanobiology & Medical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Vascular endothelial cells (ECs) are constantly exposed to blood flow-induced shear stress, which strongly influence the behaviors of neighboring vascular smooth muscle cells (VSMCs). VSMC migration is a key event in vascular wall remodeling. Current study will provide a new insight into how shear stress modulates VSMC migration in the presence of an intact endothelium. We assessed the difference of VSMC migration between VSMC/EC co-culture under static condition and in response to shear stress. With a parallel-plate co-culture flow chamber system and Transwell migration assays, we demonstrated that human ECs co-cultured with VSMCs under static condition induced VSMC migration, whereas laminar shear stress (l.5Pa, 15dynes/cm 2) applied to EC side for 12h significantly inhibited this process. The changes in VSMC migration is mainly dependent on the close interactions between ECs and VSMCs. Western blotting showed that there was a consistent correlation between the level of Akt phosphorylation and the efficacy of shear stress-mediated EC regulation VSMC migration. Wortmannin and Akti, significantly inhibited the EC-induced effect on VSMC Akt phosphrylation and migration. VSMC-EC close interaction is required for activation of PI3K/Akt, which plays a key role in VSMC migration. These results indicate that shear stress modulates VSMC migration in an endothelium-dependent fashion, exerting an atheroprotective function on the vessel wall. This research was supported by grants from the National Natural Science Foundation of China, No.10132020, No. 30070197.