scholarly journals In Silico Performance of a Recellularized Tissue-Engineered Transcatheter Aortic Valve

2019 ◽  
Vol 141 (6) ◽  
Author(s):  
Christopher Noble ◽  
Joshua Choe ◽  
Susheil Uthamaraj ◽  
Milton Deherrera ◽  
Amir Lerman ◽  
...  

Commercially available heart valves have many limitations, such as a lack of remodeling, risk of calcification, and thromboembolic problems. Many state-of-the-art tissue-engineered heart valves (TEHV) rely on recellularization to allow remodeling and transition to mechanical behavior of native tissues. Current in vitro testing is insufficient in characterizing a soon-to-be living valve due to this change in mechanical response; thus, it is imperative to understand the performance of an in situ valve. However, due to the complex in vivo environment, this is difficult to accomplish. Finite element (FE) analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to evaluate the mechanical behavior of a TEHV material before and after 6 months of implantation in a rat subdermis model. This model allows the recellularization and remodeling potential of the material to be assessed via a simple and inexpensive means prior to more complex ovine orthotropic studies. Biaxial testing was utilized to evaluate the mechanical properties, and subsequently, constitutive model parameters were fit to the data to allow mechanical performance to be evaluated via FE analysis of a full cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were then analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the FE models, this trend was continued with similar mechanical behavior in explant and native tissue groups and less compliant behavior in implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue giving confidence to our TEHV material; however, the mechanical response indicates the additional remodeling would likely occur in the aortic/pulmonary position.

Author(s):  
Snehal Chokhandre ◽  
Craig Bennetts ◽  
Jason Halloran ◽  
Robb Colbrunn ◽  
Tara Bonner ◽  
...  

The human knee joint is a complex multi-body structure, whose substructures greatly affect its mechanical response. An understanding of the multiscale mechanics of the joint is essential for the prevention and treatment of knee joint injuries and pathologies. Due to the limitations associated with in vivo experimentation, mechanical characterization of the knee joint has commonly relied on in vitro experimentation [1,2]. Predictive and descriptive studies of the mechanical function of the knee and its substructures have commonly employed computational modeling, in particular finite element (FE) analysis, which can be driven by experimental data. With the recent focus on the use of FE models of the knee joint for scientific and clinical purposes [3–5], data for model development, verification, and validation became increasingly important, especially when relying on FE analysis for decision making. An adequate representation of a joint not only depends on the specimen-specific anatomy but may also need to be informed by specimen-specific tissue properties for model development, and specimen-specific joint/tissue response to confirm model response.


2005 ◽  
Vol 127 (7) ◽  
pp. 1158-1167 ◽  
Author(s):  
Adam H. Hsieh ◽  
Diane R. Wagner ◽  
Louis Y. Cheng ◽  
Jeffrey C. Lotz

In vivo rodent tail models are becoming more widely used for exploring the role of mechanical loading on the initiation and progression of intervertebral disc degeneration. Historically, finite element models (FEMs) have been useful for predicting disc mechanics in humans. However, differences in geometry and tissue properties may limit the predictive utility of these models for rodent discs. Clearly, models that are specific for rodent tail discs and accurately simulate the disc’s transient mechanical behavior would serve as important tools for clarifying disc mechanics in these animal models. An FEM was developed based on the structure, geometry, and scale of the mouse tail disc. Importantly, two sources of time-dependent mechanical behavior were incorporated: viscoelasticity of the matrix, and fluid permeation. In addition, a novel strain-dependent swelling pressure was implemented through the introduction of a dilatational stress in nuclear elements. The model was then validated against data from quasi-static tension-compression and compressive creep experiments performed previously using mouse tail discs. Finally, sensitivity analyses were performed in which material parameters of each disc subregion were individually varied. During disc compression, matrix consolidation was observed to occur preferentially at the periphery of the nucleus pulposus. Sensitivity analyses revealed that disc mechanics was greatly influenced by changes in nucleus pulposus material properties, but rather insensitive to variations in any of the endplate properties. Moreover, three key features of the model—nuclear swelling pressure, lamellar collagen viscoelasticity, and interstitial fluid permeation—were found to be critical for accurate simulation of disc mechanics. In particular, collagen viscoelasticity dominated the transient behavior of the disc during the initial 2200s of creep loading, while fluid permeation governed disc deformation thereafter. The FEM developed in this study exhibited excellent agreement with transient creep behavior of intact mouse tail motion segments. Notably, the model was able to produce spatial variations in nucleus pulposus matrix consolidation that are consistent with previous observations in nuclear cell morphology made in mouse discs using confocal microscopy. Results of this study emphasize the need for including nucleus swelling pressure, collagen viscoelasticity, and fluid permeation when simulating transient changes in matrix and fluid stress/strain. Sensitivity analyses suggest that further characterization of nucleus pulposus material properties should be pursued, due to its significance in steady-state and transient disc mechanical response.


Author(s):  
Marinela Peto ◽  
Oscar Aguilar-Rosas ◽  
Erick Erick Ramirez-Cedillo ◽  
Moises Jimenez ◽  
Adriana Hernandez ◽  
...  

Abstract Lattice structures offer great benefits when employed in medical implants for cell attachment and growth (osseointegration), minimization of stress shielding phenomena, and weight reduction. This study is focused on a proof of concept for developing a generic shoulder hemi-prosthesis, from a patient-specific case of a 46 years old male with a tumor on the upper part of his humerus. A personalized biomodel was designed and a lattice structure was integrated in its middle portion, to lighten weight without affecting humerus’ mechanical response. To select the most appropriate lattice structure, three different configurations were initially tested: Tetrahedral Vertex Centroid (TVC), Hexagonal Prism Vertex Centroid (HPVC), and Cubic Diamond (CD). They were fabricated in resin by digital light processing and its mechanical behavior was studied via compression testing and finite element modeling (FEM). The selected structure according to the results was the HPVC, which was integrated in a digital twin of the biomodel to validate its mechanical performance through FEM but substituting the bone material model with a biocompatible titanium alloy (Ti6Al4V) suitable for prostheses fabrication. Results of the simulation showed acceptable levels of Von Mises stresses (325 MPa max.), below the elastic limit of the titanium alloys, and a better response (52 MPa max.) in a model with equivalent elastic properties, with stress performance in the same order of magnitude than the showed in bone’s material model.


1992 ◽  
Vol 15 (5) ◽  
pp. 284-288 ◽  
Author(s):  
A.C. Fisher ◽  
G.M. Bernacca ◽  
T.G. Mackay ◽  
W.R. Dimitri ◽  
R. Wilkinson ◽  
...  

This study has examined a range of methods of studying the calcification process in bovine pericardial and polyurethane biomaterials. The calcification methods include static and dynamic, in vitro and in vivo tests. The analytical methods include measurement of depletion rates of calcium and phosphate from in vitro calcifying solutions, analysis of tissue contents of calcium, histological staining of tissue sections for calcium, X-ray elemental analysis, by scanning electron microscopy, of calcium and phosphorus distributions over valve leaflets calcified in vitro under dynamic conditions. Bovine pericardium, in all test settings, calcified to a much greater degree than polyurethane biomaterials. Polyurethane extracts calcified to a greater degree than bulk polyurethanes. The test protocol used allows progress through increasily demanding calcification tests, with the possibility of eliminating unsuitable materials with tests of limited complexity and expense.


1992 ◽  
Vol 72 (3) ◽  
pp. 1149-1155 ◽  
Author(s):  
B. P. deBoisblanc ◽  
K. Meszaros ◽  
A. Burns ◽  
G. J. Bagby ◽  
S. Nelson ◽  
...  

We investigated the effect of dichloroacetate (DCA) on tension generation and carbohydrate metabolism of the rat diaphragm in vitro. Isolated diaphragms were placed in individual organ chambers and were hooked to force-displacement transducers. Net lactate production and glucose and lactate oxidation were measured in vitro. Diaphragmatic fatigue was precipitated by in vivo endotoxemic shock, by in vitro hypoxia, or by in vitro repetitive tetanic stimulation. In diaphragms isolated from endotoxemic rats, DCA increased tension generation by 30 and 20% at stimulation frequencies of 20 and 100 Hz, respectively. Associated with changes in mechanical performance, DCA reduced net lactate production by 53% after 60 min of incubation and increased glucose oxidation 54% but had no effect on lactate oxidation. During in vitro hypoxia, DCA reduced net diaphragmatic lactate production by 30% and increased glucose oxidation by 45% but did not attenuate hypoxic fatigue. DCA had no effect on tension generation during repetitive tetanic stimulation. We conclude that DCA improves in vitro diaphragmatic fatigue due to endotoxicosis but not due to hypoxia or repetitive stimulation.


1996 ◽  
Vol 76 (6) ◽  
pp. 3850-3862 ◽  
Author(s):  
M. Ulfendahl ◽  
S. M. Khanna ◽  
A. Fridberger ◽  
A. Flock ◽  
B. Flock ◽  
...  

1. With the use of an in vitro preparation of the guinea pig temporal bone, in which the apical turns of the cochlea are exposed, the mechanical and electrical responses of the cochlea in the low-frequency regions were studied during sound stimulation. 2. The mechanical characteristics were investigated in the fourth and third turns of the cochlea with the use of laser heterodyne interferometry, which allows the vibratory responses of both sensory and supporting cells to be recorded. The electrical responses, which can be maintained for several hours, were recorded only in the most apical turn. 3. In the most apical turn, the frequency locations and shapes of the mechanical and electrical responses were very similar. 4. The shapes of the tuning curves and the spatial locations of the frequency maxima in the temporal bone preparation compared very favorably with published results from in vivo recordings of hair cell receptor potentials and sound-induced vibrations of the Reissner's membrane. 5. Compressive nonlinearities were present in both the mechanical and the electrical responses at moderate sound pressure levels. 6. The mechanical tuning changed along the length of the cochlea, the center frequencies in the fourth and third turns being approximately 280 and 570 Hz, respectively. 7. The mechanical responses of sensory and supporting cells were almost identical in shape but differed significantly in amplitude radially across the reticular lamina.


2009 ◽  
Vol 131 (5) ◽  
Author(s):  
Joel L. Lanovaz ◽  
Randy E. Ellis

Knowledge of the behavior and mechanics of a total knee replacement (TKR) in an in vivo environment is key to optimizing the functional outcomes of the implant procedure. Computational modeling has shown to be an important tool for investigating biomechanical variables that are difficult to address experimentally. To assist in examining TKR mechanics, a dynamic finite-element model of a TKR is presented. The objective of the study was to develop and evaluate a model that could simulate full knee motion using a physiologically consistent quadriceps action, without prescribed joint kinematics. The model included tibiofemoral (TFJs) and patellofemoral joints (PFJs), six major ligament bundles and was driven by a uni-axial representation of a quadricep muscle. An initial parameter screening analysis was performed to assess the relative importance of 31 different model parameters. This analysis showed that ligament insertion location and initial ligament strain were significant factors affecting simulated joint kinematics and loading, with the contact friction coefficient playing a lesser role and ligament stiffness having little effect. The model was then used to simulate in vitro experiments utilizing a flexed-knee-stance testing rig. General model performance was assessed by comparing simulation results with experimentally measured kinematics and tibial reaction forces collected from two implanted specimens. The simulations were able to reproduce experimental differences observed between the test specimens and were able to accurately predict trends seen in the tibial reaction loads. The simulated kinematics of the TFJ and PFJ were less consistent when compared with experimental data but still reproduced many trends.


2005 ◽  
Vol 288-289 ◽  
pp. 355-358
Author(s):  
Y. Cao ◽  
Bo Zhang ◽  
Li Ping Wang ◽  
Qiang Lin ◽  
Xu Dong Li ◽  
...  

Plasma-sprayed hydroxyapatite coating on metal substrate was prepared. Two kind of post-treatment methods were been applied to the coating, treatment in air at 650°C for 30 min and treatment in water vapor at 125°C with a pressure of 0.15MPa for 6 hours. XRD showed that the HA nanocrystals increased after water vapor treatment. The interfacial tensile bond strength between HA and substrate was 45.0±1.82MPa, 39.1±1.27MPa and 30.3±1.61MPa for as-received coatings, water vapor treated coatings and heated in air coatings, respectively. 3 months after implantation in dogs limbs, the push-out strength between implants and bone was 11.27±2.71MPa, 11.63±3.11MPa, 23.92± 2.01MPa and 18.8± 1.82MPa for pure Ti implants, as-received coating implants, water vapor treated implants and heated in air implants, respectively. The results showed that the post-water vapor treated HA coating have better mechanical behavior in vitro and in vivo


Author(s):  
João S. Soares ◽  
Trung B. Le ◽  
Fotis Sotiropoulos ◽  
Michael S. Sacks

Living tissue engineered heart valves (TEHV) may circumvent ongoing problems in pediatric valve replacements, offering optimum hemodynamic performance and the potential for growth, remodeling, and self-repair [1]. TEHV have been constructed by seeding vascular-derived autologous cells onto biodegradable scaffolds and exhibited enhanced extracellular matrix (ECM) development when cultured under pulsatile flow conditions in-vitro [2]. After functioning successfully for up to 8 months in the pulmonary circulation of growing lambs, TEHV underwent extensive in vivo remodeling and structural evolution and have demonstrated the feasibility of engineering living heart valves in vitro [3]. The employment of novel cell sources, which are clinically obtainable in principle such as bone marrow-derived mesenchymal stem cells (MSCs), is key to achieve viable clinical application [4].


1991 ◽  
Vol 332 (1264) ◽  
pp. 191-198 ◽  

Scaling of heart ventricle mass and body mass in the haemoglobinless Antarctic fish Chionodraco hamatus Lönnberg shows a relationship similar to those reported for other ‘cardiomegalic ’ icefish ( Chaenocephalus aceratus and Channichthys rhinoceratus ). An in vitro preparation of the heart of C. hamatus was set up to investigate the mechanical performance of this heart at different preloads and afterloads. It appears that this heart is well adapted to working within a range of preloads varying from —0.07 to —0.04 kPa, while it is unable to sustain increases of afterloads higher than 3.0 kPa. As in other teleosts, heart rate is unaffected by changes in preload and afterload. Increase in temperature from 0.5 to 5.8 °C affects heart rate whereas stroke volume is unaffected. On the whole, the in vitro data are similar to those in vivo measured in another icefish, C. aceratus and show that the heart of C. hamatus works as a typical volume pump. This is discussed in relation to both the structural constraints related to the cardiac design of this icefish and the biology of this unique vertebrate.


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