scholarly journals Hemodynamics and Mechanobiology of Aortic Valve Inflammation and Calcification

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Kartik Balachandran ◽  
Philippe Sucosky ◽  
Ajit P. Yoganathan
Keyword(s):  
Aortic Valve ◽  
Ex Vivo ◽  
Axial Stress ◽  
Biological Response ◽  
Shear Stresses ◽  
Mechanical Stimuli ◽  
Valve Remodeling ◽  
Valve Pathology ◽  
Opening And Closing

Cardiac valves function in a mechanically complex environment, opening and closing close to a billion times during the average human lifetime, experiencing transvalvular pressures and pulsatile and oscillatory shear stresses, as well as bending and axial stress. Although valves were originally thought to be passive pieces of tissue, recent evidence points to an intimate interplay between the hemodynamic environment and biological response of the valve. Several decades of study have been devoted to understanding these varied mechanical stimuli and how they might induce valve pathology. Here, we review efforts taken in understanding the valvular response to its mechanical milieu and key insights gained fromin vitroandex vivowhole-tissue studies in the mechanobiology of aortic valve remodeling, inflammation, and calcification.

Fluid Shear Stress Characteristics of the Ventricular Surface Versus the Aortic Surface of the Aortic Valve: An In Vitro Study

2011 ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Ajit P. Yoganathan
Keyword(s):  
Aortic Valve ◽  
Fluid Shear Stress ◽  
Ex Vivo ◽  
Shear Stresses ◽  
Dependent Manner ◽  
Aortic Valve Calcification ◽  
Fluid Shear ◽  
Valve Calcification ◽  
Ventricular Surface

Aortic valve calcification is a degenerative disease with high prevalence, especially amongst the elderly, and is a major cause of morbidity and mortality. Ex vivo experiments has shown that aortic valve leaflets are sensitive to their mechanical environment in a magnitude dependent manner. Fluid shear stresses, specifically, has been shown to affect inflammatory and remodeling responses relevant to aortic valve calcification [1,2]. Consequently, it has been proposed that the phenomenon of diseased calcium nodules developing exclusively on the aortic surface as opposed to the ventricular surface is due to the exposure of the aortic surface to disturbed shear stresses, whereas undisturbed shear stresses on the ventricular surface do not trigger calcification [3,4]. Additionally, it has been observed that the non-coronary leaflet of the AV is more susceptible to calcification, which is hypothesized to be due to reduced shear stresses from the lack of diastolic coronary flow [5].

Pre-Clinical Biocompatibility Testing of Peritoneal Dialysis Solutions

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 5-9 ◽  
Author(s):  
C.J. Holmes
Keyword(s):  
Peritoneal Dialysis ◽  
Screening Program ◽  
Ex Vivo ◽  
Biological Response ◽  
Cell Types ◽  
Hierarchical Level ◽  
Clinical Phase ◽  
Biocompatibility Testing

Pre-clinical biocompatibility testing of peritoneal dialysis (PD) solutions has become an integral part of new solution development. The construction of a pre-clinical screening program for solution biocompatibility should take a hierarchical approach, starting with in vitro cell viability and function assays. The selection of cell types and assay systems for the in vitro studies should be broad enough to permit a balanced interpretation. Whenever possible, animal models are recommended for the next hierarchical level of testing, followed by human ex vivo study designs. Designs of the latter sort provide evidence that a new solution formulation is exerting an altered biological response in vivo; the response is not purely an in vitro artifact or restricted to a given animal species. This article discusses the various approaches available for biocompatibility testing during the pre-clinical phase of solution development, with an emphasis on the advantages and drawbacks of each method.

An Innovative Ex Vivo Vascular Bioreactor as Comprehensive Tool to Study the Behavior of Native Blood Vessels Under Physiologically Relevant Conditions

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Noemi Vanerio ◽  
Marco Stijnen ◽  
Bas A. J. M. de Mol ◽  
Linda M. Kock
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Ultrasound Imaging ◽  
Ex Vivo ◽  
Biological Response ◽  
Vessel Diameter ◽  
Tissue Growth ◽  
In Vivo Models

Abstract Ex vivo systems represent important models to study vascular biology and to test medical devices, combining the advantages of in vitro and in vivo models such as controllability of parameters and the presence of biological response, respectively. The aim of this study was to develop a comprehensive ex vivo vascular bioreactor to long-term culture and study the behavior of native blood vessels under physiologically relevant conditions. The system was designed to allow for physiological mechanical loading in terms of pulsatile hemodynamics, shear stress, and longitudinal prestretch and ultrasound imaging for vessel diameter and morphology evaluation. In this first experience, porcine carotid arteries (n = 4) from slaughterhouse animals were cultured in the platform for 10 days at physiological temperature, CO2 and humidity using medium with blood-mimicking viscosity, components, and stability of composition. As expected, a significant increase in vessel diameter was observed during culture. Flow rate was adjusted according to diameter values to reproduce and maintain physiological shear stress, while pressure was kept physiological. Ultrasound imaging showed that the morphology and structure of cultured arteries were comparable to in vivo. Histological analyses showed preserved endothelium and extracellular matrix and neointimal tissue growth over 10 days of culture. In conclusion, we have developed a comprehensive pulsatile system in which a native blood vessel can be cultured under physiological conditions. The present model represents a significant step toward ex vivo testing of vascular therapies, devices, drug interaction, and as basis for further model developments.

scholarly journals Sinus Hemodynamics in Representative Stenotic Native Bicuspid and Tricuspid Aortic Valves: An In-Vitro Study

Fluids ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. 56 ◽  
Author(s):  
Hoda Hatoum ◽  
Lakshmi Prasad Dasi
Keyword(s):  
Aortic Valve ◽  
In Vitro Study ◽  
Patient Specific ◽  
Shear Stresses ◽  
Flow Shear ◽  
Aortic Sinus ◽  
Image Velocimetry ◽  
3D Printed ◽  
Sinus Flow

(1) The study’s objective is to assess sinus hemodynamics differences between stenotic native bicuspid aortic valve (BAV) and native tricuspid aortic valve (TrAV) sinuses in order to assess sinus flow shear and vorticity dynamics in these common pathological states of the aortic valve. (2) Representative patient-specific aortic roots with BAV and TrAV were selected, segmented, and 3D printed. The flow dynamics within the sinus were assessed in-vitro using particle image velocimetry in a left heart simulator at physiological pressure and flow conditions. Hemodynamic data calculations, vortex tracking, shear stress probability density functions and sinus washout calculations based on Lagrangian particle tracking were performed. (3) (a) At peak systole, velocity and vorticity in BAV reach 0.67 ± 0.02 m/s and 374 ± 5 s−1 versus 0.49 ± 0.03 m/s and 293 ± 3 s−1 in TrAV; (b) Aortic sinus vortex is slower to form but conserved in BAV sinus; (c) BAV shear stresses exceed those of TrAV (1.05 Pa versus 0.8 Pa); (d) Complete TrAV washout was achieved after 1.5 cycles while it was not for BAV. 4) In conclusion, sinus hemodynamics dependence on the different native aortic valve types and sinus morphologies was clearly highlighted in this study.

scholarly journals Preparation of phospholipid-based polycarbonate urethanes for potential applications of blood-contacting implants

2020 ◽  
Vol 7 (5) ◽  
pp. 491-504
Author(s):  
Peichuang Li ◽  
Wanhao Cai ◽  
Xin Li ◽  
Kebing Wang ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Microphase Separation ◽  
Blood Compatibility ◽  
Ex Vivo ◽  
Raw Materials ◽  
Direct Synthesis ◽  
Animal Experiments ◽  
Biological Response ◽  
Superior Performance ◽  
Scanning Calorimetry

Abstract Polyurethanes are widely used in interventional devices due to the excellent physicochemical property. However, non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices. Herein, a novel phospholipid-based polycarbonate urethanes (PCUs) were developed via two-step solution polymerization by direct synthesis based on functional raw materials. Furthermore, PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface. The results of stress–strain curves exhibited excellent tensile properties of PCUs films. Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender, leading to different biological response. In vitro blood compatibility tests including bovine serum albumin adsorption, fibrinogen adsorption and denaturation, platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples. Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability. Finally, animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility. These results high light the strong anti-adhesion property of phospholipid-based PCUs films, which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.

Abstract 16123: In Vitro Valve-on-chip Platform to Assess the Effects of Hemodynamic and Mechanical Stimuli on Early Calcific Disease Progression

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ishita Tandon ◽  
Cody Gish ◽  
Nasya Sturdivant ◽  
Asya Ozkizilcik ◽  
Celeste Dunn ◽  
...  
Keyword(s):  
Disease Progression ◽  
Nodule Formation ◽  
Shear Stresses ◽  
Matrix Remodeling ◽  
Mechanical Stimuli ◽  
Native Valve ◽  
Hemodynamic Forces ◽  
Disease Initiation ◽  
On Chip

Introduction: Calcific aortic valve disease (CAVD) involves mechanical stress, endothelial dysfunction, matrix remodeling, and mineral deposition. Complex mechanical and hemodynamic environment around the valve closely affects its function, biology, and disease. However, the exact role of these forces in regulating cellular dysfunction during disease initiation is yet to be elucidated. Methods and Results: We developed a 3D valve-on-chip (VOC) model that encompasses cell-cell and cell-matrix interactions, flow shear stresses and cyclic strains, better mimicking the native valve. The multilayered VOC construct was built in house using photolithography and soft lithography and a silicon based polymer (Fig.1A). Valve endothelial cells (VECs) are seeded in a monolayer on a porous PDMS membrane (Fig.B) which separates the VECs from the a matrigel-collagen semi interpenetrating hybrid gel housing valve interstitial cells (VICs) (Fig.3C). We simulated either static or 20% (pathological) strain under quiescent or osteogenic conditions. Osteogenic VICs demonstrated nodule formation (Fig.1D) and had reduced redox ratios in 20% stretch conditions suggesting disease progression (Fig.1E,F). Effect of mechanical and hemodynamic forces on structure, function, and phenotypic changes in VECs and VICs particularly during disease initiation will be further assessed. Conclusions: This VOC model for VEC-VIC co-culture better mimics the native valve environment and can be used to study the early disease mechanisms. The VOC platform can be used as a drug testing tool and aid in development of treatment strategies through efficient employment in the laboratory. Further exploring the effect of mechanical and hemodynamic forces may reveal mechanosensitive signaling cascades involved in disease progression, which can be targeted for CAVD therapeutics.

scholarly journals The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface

2012 ◽  
Vol 303 (6) ◽  
pp. H721-H731 ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Nikolai Vasilyev ◽  
Ajit P. Yoganathan
Keyword(s):  
Aortic Valve ◽  
Bicuspid Aortic Valve ◽  
High Frequency ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Flow Loop ◽  
Model Flow ◽  
Image Velocimetry ◽  
Vitro Model

The bicuspid aortic valve (BAV) is a common congenital malformation of the aortic valve (AV) affecting 1% to 2% of the population. The BAV is predisposed to early degenerative calcification of valve leaflets, and BAV patients constitute 50% of AV stenosis patients. Although evidence shows that genetic defects can play a role in calcification of the BAV leaflets, we hypothesize that drastic changes in the mechanical environment of the BAV elicit pathological responses from the valve and might be concurrently responsible for early calcification. An in vitro model of the BAV was constructed by surgically manipulating a native trileaflet porcine AV. The BAV valve model and a trileaflet AV (TAV) model were tested in an in vitro pulsatile flow loop mimicking physiological hemodynamics. Laser Doppler velocimetry was used to make measurements of fluid shear stresses on the leaflet of the valve models using previously established methodologies. Furthermore, particle image velocimetry was used to visualize the flow fields downstream of the valves and in the sinuses. In the BAV model, flow near the leaflets and fluid shear stresses on the leaflets were much more unsteady than for the TAV model, most likely due to the moderate stenosis in the BAV and the skewed forward flow jet that collided with the aorta wall. This additional unsteadiness occurred during mid- to late-systole and was composed of cycle-to-cycle magnitude variability as well as high-frequency fluctuations about the mean shear stress. It has been demonstrated that the BAV geometry can lead to unsteady shear stresses under physiological flow and pressure conditions. Such altered shear stresses could play a role in accelerated calcification in BAVs.

Experimental Technique of Measuring Dynamic Fluid Shear Stress on the Aortic Surface of the Aortic Valve Leaflet

2011 ◽  
Vol 133 (6) ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Ajit P. Yoganathan
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Steady Flow ◽  
Fluid Shear Stress ◽  
Shear Stresses ◽  
Straight Tube ◽  
Valve Leaflet ◽  
Fluid Shear ◽  
Valve Model

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5dyn/cm2) but elevated to its peak during mid to late systole at about 18–20 dyn/cm2. Low magnitude shear stress (<5dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.

The Congenital Bicuspid Aortic Valve Can Experience Fluid Shear Stresses Associated With Sclerosis

2011 ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Swetha Rathan ◽  
Gowthami Tamilselvan ◽  
Nikolay V. Vasilyev ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Ex Vivo ◽  
The Elderly ◽  
Shear Stresses ◽  
Dependent Manner ◽  
Aortic Valve Calcification ◽  
Fluid Shear ◽  
Valve Calcification ◽  
Mechanical Environment ◽  
High Prevalence

Aortic valve calcification is a degenerative disease with high prevalence, especially amongst the elderly, and is a major cause of morbidity and mortality. Ex vivo experiments has shown that aortic valve leaflets are sensitive to their mechanical environment in a magnitude dependent manner. Fluid shear stresses, specifically, has been shown to affect inflammatory and remodeling responses relevant to aortic valve calcification [1,2].

scholarly journals Ionic shape-morphing microrobotic end-effectors for environmentally adaptive targeting, releasing, and sampling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhiqiang Zheng ◽  
Huaping Wang ◽  
Lixin Dong ◽  
Qing Shi ◽  
Jianing Li ◽  
...  
Keyword(s):  
Smart Materials ◽  
Ex Vivo ◽  
Magnetic Microspheres ◽  
Shape Transformation ◽  
Shape Morphing ◽  
Ph Values ◽  
End Effectors ◽  
Opening And Closing ◽  
Ionic Density

AbstractShape-morphing uses a single actuation source for complex-task-oriented multiple patterns generation, showing a more promising way than reconfiguration, especially for microrobots, where multiple actuators are typically hardly available. Environmental stimuli can induce additional causes of shape transformation to compensate the insufficient space for actuators and sensors, which enriches the shape-morphing and thereby enhances the function and intelligence as well. Here, making use of the ionic sensitivity of alginate hydrogel microstructures, we present a shape-morphing strategy for microrobotic end-effectors made from them to adapt to different physiochemical environments. Pre-programmed hydrogel crosslinks were embedded in different patterns within the alginate microstructures in an electric field using different electrode configurations. These microstructures were designed for accomplishing tasks such as targeting, releasing and sampling under the control of a magnetic field and environmental ionic stimuli. In addition to structural flexibility and environmental ion sensitivity, these end-effectors are also characterized by their complete biodegradability and versatile actuation modes. The latter includes global locomotion of the whole end-effector by self-trapping magnetic microspheres as a hitch-hiker and the local opening and closing of the jaws using encapsulated nanoparticles based on local ionic density or pH values. The versatility was demonstrated experimentally in both in vitro environments and ex vivo in a gastrointestinal tract. Global locomotion was programmable and the local opening and closing was achieved by changing the ionic density or pH values. This ‘structural intelligence’ will enable strategies for shape-morphing and functionalization, which have attracted growing interest for applications in minimally invasive medicine, soft robotics, and smart materials.

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