Computational Prediction of Fluid Induced Stress States in Dynamically Conditioned Engineered Heart Valve Tissues

2012 ◽  
Author(s):  
M. Salinas ◽  
D. Schmidt ◽  
R. Lange ◽  
M. Libera ◽  
S. Ramaswamy
Keyword(s):  
Shear Stress ◽  
Steady Flow ◽  
Heart Valve ◽  
Heart Valves ◽  
Critical Role ◽  
Computational Prediction ◽  
Mechanical Conditioning ◽  
Custom Made ◽  
Stress Environments

There is extensive documented evidence that mechanical conditioning plays a significant role in the development of tissue grown in-vitro for heart valve scaffolds [1–3]. Modern custom made bioreactors have been used to study the mechanobiology of engineered heart valve tissues [1]. Specifically fluid-induced shears stress patterns may play a critical role in up-regulating extracellular matrix secretion by progenitor cell sources such as bone marrow derived stem cells (BMSCs) [2] and increasing the possibility of cell differentiation towards a heart valve phenotype. We hypothesize that specific biomimetic fluid induced shear stress environments, particularly oscillatory shear stress (OSS), have significant effects on BMSCs phenotype and formation rates. As a first step here, we attempt to quantify and delineate the entire 3-D flow field by developing a CFD model to predict the fluid induced shear stress environments on engineered heart valves tissue under quasi-static steady flow and dynamic steady flow conditions.

scholarly journals Recellularization of decellularized heart valves: Progress toward the tissue-engineered heart valve

2017 ◽  
Vol 8 ◽  
pp. 204173141772632 ◽  
Author(s):  
Mitchell C VeDepo ◽  
Michael S Detamore ◽  
Richard A Hopkins ◽  
Gabriel L Converse
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Mechanical Conditioning ◽  
New Era ◽  
Processing Strategies ◽  
Tissue Engineered Heart Valve ◽  
Tissue Engineered Heart Valves

The tissue-engineered heart valve portends a new era in the field of valve replacement. Decellularized heart valves are of great interest as a scaffold for the tissue-engineered heart valve due to their naturally bioactive composition, clinical relevance as a stand-alone implant, and partial recellularization in vivo. However, a significant challenge remains in realizing the tissue-engineered heart valve: assuring consistent recellularization of the entire valve leaflets by phenotypically appropriate cells. Many creative strategies have pursued complete biological valve recellularization; however, identifying the optimal recellularization method, including in situ or in vitro recellularization and chemical and/or mechanical conditioning, has proven difficult. Furthermore, while many studies have focused on individual parameters for increasing valve interstitial recellularization, a general understanding of the interacting dynamics is likely necessary to achieve success. Therefore, the purpose of this review is to explore and compare the various processing strategies used for the decellularization and subsequent recellularization of tissue-engineered heart valves.

In Vitro hydrodynamic evaluation of prosthetic polymer heart valves in steady flow

KSME Journal ◽  
1993 ◽  
Vol 7 (3) ◽  
pp. 223-230
Author(s):  
B. C. Pak ◽  
B. S. Cho ◽  
B. J. Baek ◽  
C. S. Kim ◽  
B. G. Min
Keyword(s):  
Steady Flow ◽  
Heart Valves ◽  
Hydrodynamic Evaluation

scholarly journals Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?

2020 ◽  
Vol 31 (12) ◽  
Author(s):  
Adel F. Badria ◽  
Petros G. Koutsoukos ◽  
Dimosthenis Mavrilas
Keyword(s):  
Heart Valve ◽  
Clinical Studies ◽  
Heart Valves ◽  
Early Stage ◽  
Anticoagulation Therapy ◽  
Complex Nature ◽  
In Silico Studies ◽  
Decellularized Tissue ◽  
Tissue Engineered Heart Valves

AbstractCardiovascular diseases are the first cause of death worldwide. Among different heart malfunctions, heart valve failure due to calcification is still a challenging problem. While drug-dependent treatment for the early stage calcification could slow down its progression, heart valve replacement is inevitable in the late stages. Currently, heart valve replacements involve mainly two types of substitutes: mechanical and biological heart valves. Despite their significant advantages in restoring the cardiac function, both types of valves suffered from serious drawbacks in the long term. On the one hand, the mechanical one showed non-physiological hemodynamics and the need for the chronic anticoagulation therapy. On the other hand, the biological one showed stenosis and/or regurgitation due to calcification. Nowadays, new promising heart valve substitutes have emerged, known as decellularized tissue-engineered heart valves (dTEHV). Decellularized tissues of different types have been widely tested in bioprosthetic and tissue-engineered valves because of their superior biomechanics, biocompatibility, and biomimetic material composition. Such advantages allow successful cell attachment, growth and function leading finally to a living regenerative valvular tissue in vivo. Yet, there are no comprehensive studies that are covering the performance of dTEHV scaffolds in terms of their efficiency for the calcification problem. In this review article, we sought to answer the question of whether decellularized heart valves calcify or not. Also, which factors make them calcify and which ones lower and/or prevent their calcification. In addition, the review discussed the possible mechanisms for dTEHV calcification in comparison to the calcification in the native and bioprosthetic heart valves. For this purpose, we did a retrospective study for all the published work of decellularized heart valves. Only animal and clinical studies were included in this review. Those animal and clinical studies were further subcategorized into 4 categories for each depending on the effect of decellularization on calcification. Due to the complex nature of calcification in heart valves, other in vitro and in silico studies were not included. Finally, we compared the different results and summed up all the solid findings of whether decellularized heart valves calcify or not. Based on our review, the selection of the proper heart valve tissue sources (no immunological provoking residues), decellularization technique (no damaged exposed residues of the decellularized tissues, no remnants of dead cells, no remnants of decellularizing agents) and implantation techniques (avoiding suturing during the surgical implantation) could provide a perfect anticalcification potential even without in vitro cell seeding or additional scaffold treatment.

scholarly journals Stereoscopic PIV of Steady Flow Through a Bileaflet Mechanical Heart Valve

2008 ◽  
Author(s):  
C. Hutchison ◽  
P. E. Sullivan ◽  
C. R. Ethier
Keyword(s):  
Steady Flow ◽  
Heart Valve ◽  
Heart Valves ◽  
Mechanical Heart Valve ◽  
Three Dimensional ◽  
Flow Characteristics ◽  
Shear Stresses ◽  
Stereoscopic Piv ◽  
Bileaflet Mechanical Heart Valve ◽  
Component Particle

Each year over 180,000 mechanical heart valves are implanted worldwide, with the bileaflet mechanical heart valve (BiMHV) accounting for approximately 85% of all valve replacements [1,2]. Although much improved from previous valve designs, aortic BiMHV design is far from ideal, and serious complications such as thromboembolism and hemolysis often result. Hemolysis and platelet activation are thought to be caused by turbulent Reynolds shear stresses in the flow [1]. Numerous previous studies have examined aortic BiMHV flow using LDA and two component Particle Image Velocimetry (PIV), and have shown the flow to be complex and three-dimensional [3,4]. Stereoscopic PIV (SPIV) can obtain all three velocity components on a flow plane, and hence has the potential to provide better understanding of three dimensional flow characteristics. The objective of the current study was to use SPIV to measure steady flow, including turbulence properties, downstream of a BiMHV in a modeled aorta. The resulting dataset will be useful for CFD model validation, and the intent is to make it publicly available.

scholarly journals A Novel Bioreactor for Mechanobiological Studies of Engineered Heart Valve Tissue Formation Under Pulmonary Arterial Physiological Flow Conditions

2014 ◽  
Vol 136 (12) ◽  
Author(s):  
Sharan Ramaswamy ◽  
Steven M. Boronyak ◽  
Trung Le ◽  
Andrew Holmes ◽  
Fotis Sotiropoulos ◽  
...  
Keyword(s):  
Shear Stress ◽  
Laminar Flow ◽  
Heart Valve ◽  
Tissue Formation ◽  
Flow Conditions ◽  
Physiological Flow ◽  
Valve Tissue ◽  
Engineered Tissue ◽  
Heart Valve Tissue

The ability to replicate physiological hemodynamic conditions during in vitro tissue development has been recognized as an important aspect in the development and in vitro assessment of engineered heart valve tissues. Moreover, we have demonstrated that studies aiming to understand mechanical conditioning require separation of the major heart valve deformation loading modes: flow, stretch, and flexure (FSF) (Sacks et al., 2009, "Bioengineering Challenges for Heart Valve Tissue Engineering," Annu. Rev. Biomed. Eng., 11(1), pp. 289–313). To achieve these goals in a novel bioreactor design, we utilized a cylindrical conduit configuration for the conditioning chamber to allow for higher fluid velocities, translating to higher shear stresses on the in situ tissue specimens while retaining laminar flow conditions. Moving boundary computational fluid dynamic (CFD) simulations were performed to predict the flow field under combined cyclic flexure and steady flow (cyclic-flex-flow) states using various combinations of flow rate, and media viscosity. The device was successfully constructed and tested for incubator housing, gas exchange, and sterility. In addition, we performed a pilot experiment using biodegradable polymer scaffolds seeded with bone marrow derived stem cells (BMSCs) at a seeding density of 5 × 106 cells/cm2. The constructs were subjected to combined cyclic flexure (1 Hz frequency) and steady flow (Re = 1376; flow rate of 1.06 l/min (LPM); shear stress in the range of 0–9 dynes/cm2) for 2 weeks to permit physiological shear stress conditions. Assays revealed significantly (P < 0.05) higher amounts of collagen (2051 ± 256 μg/g) at the end of 2 weeks in comparison to similar experiments previously conducted in our laboratory but performed at subphysiological levels of shear stress (<2 dynes/cm2; Engelmayr et al., 2006, "Cyclic Flexure and Laminar Flow Synergistically Accelerate Mesenchymal Stem Cell-Mediated Engineered Tissue Formation: Implications for Engineered Heart Valve Tissues," Biomaterials, 27(36), pp. 6083–6095). The implications of this novel design are that fully coupled or decoupled physiological flow, flexure, and stretch modes of engineered tissue conditioning investigations can be readily accomplished with the inclusion of this device in experimental protocols on engineered heart valve tissue formation.

scholarly journals The Adaptor Protein Nck1, but not Nck2, Mediates Shear Stress-Induced Endothelial Permeability

2019 ◽  
Author(s):  
Mabruka Alfaidi ◽  
Umesh Bhattarai ◽  
Elizabeth D Cockerham ◽  
A.W. Orr
Keyword(s):  
Shear Stress ◽  
Vascular Permeability ◽  
Pore Formation ◽  
Critical Role ◽  
Endothelial Permeability ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Disturbed Flow

AbstractAlteration in hemodynamic shear stress at atheroprone sites promotes endothelial paracellular pore formation and permeability. Previously, we have reported that a peptide inhibitor to Nck prevented shear stress-induced p21 activated kinase (PAK) activation and endothelial permeability. However, the specificity of this peptide is unclear, and the role of individual Nck isoforms remain unknown. Here, we show that genetic deletion of Nck1/2 adaptor proteins significantly ameliorates shear stress induced permeability, and selective isoform depletion suggests distinct signaling mechanisms. Only Nck1 deletion significantly reduces flow-induced paracellular pore formation and permeability, whereas Nck2 depletion has no significant effects. Additionally, Nck1 reexpression, but not Nck2, restores shear stress-induced permeability in Nck1/2 knockout cells, confirming the non-compensating roles. In vivo, using the partial carotid ligation model of disturbed flow, Nck1 knockout prevented the increase in vascular permeability, as assessed by both Evans blue extravasation and leakage of plasma fibrinogen into the vessel wall. Domain swap experiments mixing SH2 (phosphotyrosine binding) and SH3 (proline rich binding) domains between Nck1 and Nck2 showed a dispensable role for SH2 domains but a critical role for the Nck1 SH3 domains in rescuing shear stress-induced endothelial permeability. Consistent with this, both Nck1 and Nck2 bind to PECAM-1 (SH2 dependent) in response to shear stress, but only Nck1 ablation interferes with shear stress-induced PAK2 activation (SH3 dependent). This work provides the first evidence that Nck1 and Nck2 play distinct roles in flow-induced vascular permeability.New and NoteworthyThe present study shows a specific role for Nck1 in endothelial permeability in response to shear stress. Using in vitro and in vivo models, we demonstrate improvement in endothelial barrier integrity in cells subjected to disturbed flow only following Nck1 but not Nck2 deletion. Selective Nck1 inhibition may limit endothelial permeability at sites of disturbed flow to reduce atherosclerosis without affecting angiogenesis, which requires both Nck1 and Nck2 inhibition.

scholarly journals Polyisobutylene-Based Thermoplastic Elastomers for Manufacturing Polymeric Heart Valve Leaflets: In Vitro and In Vivo Results

2019 ◽  
Vol 9 (22) ◽  
pp. 4773 ◽  
Author(s):  
Evgeny Ovcharenko ◽  
Maria Rezvova ◽  
Pavel Nikishau ◽  
Sergei Kostjuk ◽  
Tatiana Glushkova ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Heart Valve ◽  
Heart Valves ◽  
Reference Sample ◽  
Sample Surface ◽  
Thermoplastic Elastomers ◽  
Water Contact ◽  
Promising Alternative

Superior polymers represent a promising alternative to mechanical and biological materials commonly used for manufacturing artificial heart valves. The study is aimed at assessing poly(styrene-block-isobutylene-block-styrene) (SIBS) properties and comparing them with polytetrafluoroethylene (Gore-texTM, a reference sample). Surface topography of both materials was evaluated with scanning electron microscopy and atomic force microscopy. The mechanical properties were measured under uniaxial tension. The water contact angle was estimated to evaluate hydrophilicity/hydrophobicity of the study samples. Materials’ hemocompatibility was evaluated using cell lines (Ea.hy 926), donor blood, and in vivo. SIBS possess a regular surface relief. It is hydrophobic and has lower strength as compared to Gore-texTM (3.51 MPa vs. 13.2/23.8 MPa). SIBS and Gore-texTM have similar hemocompatibility (hemolysis, adhesion, and platelet aggregation). The subcutaneous rat implantation reports that SIBS has a lower tendency towards calcification (0.39 mg/g) compared with Gore-texTM (1.29 mg/g). SIBS is a highly hemocompatible material with a promising potential for manufacturing heart valve leaflets, but its mechanical properties require further improvements. The possible options include the reinforcement with nanofillers and introductions of new chains in its structure.

Tissue Factor Activity Is Upregulated in Human Endothelial Cells Exposed to Oscillatory Shear Stress

2002 ◽  
Vol 87 (06) ◽  
pp. 1062-1068 ◽  
Author(s):  
Paolo Silacci ◽  
Karima Bouzourene ◽  
François Daniel ◽  
Hans Brunner ◽  
Daniel Hayoz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Protein Expression ◽  
Tissue Factor ◽  
Critical Role ◽  
Oscillatory Shear ◽  
Human Endothelial Cells ◽  
Static Conditions ◽  
Oscillatory Shear Stress

SummaryHemodynamic forces play a critical role in the pathogenesis of atherosclerosis as evidenced by the focal nature of the disease. Oscillatory shear stress characterizes the hemodynamic environment of plaque-prone areas as opposed to unidirectional shear stress typical of plaque-free areas. These particular flow conditions modulate atherosclerosis-related genes. Tissue factor (TF) initiates blood coagulation, contributes to vascular remodeling, and is therefore a potential contributor in the development/progression of atherosclerosis. We investigated the effect of oscillatory and unidirectional flows on TF using an in vitro perfusion system. Human endothelial cells exposed for 24 h to oscillatory shear stress, significantly increased TF mRNA, and TF protein expression (1.5-and 1.75-fold, respectively, p <0.01), and surface TF activity (twofolds-increase). Expression of TF inhibitor (TFPI), mRNA and protein, remained unchanged as compared to static conditions. Conversely, cells exposed to unidirectional shear, showed a decrease in TF activity with a significant increase in TFPI mRNA and protein expression (1.5-and 1.8-fold, respectively, p <0.01). These results show for the first time that pulsatile oscillatory shear stress induces a procoagulant phenotype of endothelial cells which may favor formation/progression of atherothrombotic lesions.

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