Special Issue "Advances in Biological Tissue Biomechanics"

A special issue of Bioengineering (ISSN 2306-5354).

Deadline for manuscript submissions: closed (30 April 2019).

Special Issue Editors

Dr. Chung-Hao Lee
Website
Guest Editor
School of Aerospace and Mechanical Engineering Gallogly College of Engineering The University of Oklahoma Norman, OK 73019
Interests: cardiovascular heart valve biomechanics; multi-scale modeling; biomaterials design
Special Issues and Collections in MDPI journals
Dr. Jun Liao
Website
Guest Editor
Associate Professor, Department of Bioengineering, University of Texas at Arlington, TX, USA
Interests: tissue biomechanics; tissue regeneration

Special Issue Information

Dear Colleagues,

Advanced experimental and computational biomechanics have become essential components for a better understanding of the physiological and pathological conditions of biological tissues in the human body. Recent advances in medical imaging modalities, image segmentation, tissue characterization experiments, and predictive computer simulations have made major contributions to transforming current therapeutic paradigms towards the facilitations of patient-specific diagnostics and individualized surgery planning.

This Special Issue on “Advances in Biological Tissue Biomechanics”, therefore, will focus on original research papers and comprehensive reviews, dealing with cutting-edge experimental and computational methodologies for multiscale biomechanical investigations of biological tissues in the human body system. Topics of interest for this Special Issue include, but are not limited to, the following:

  1. Advanced experimental techniques for characterizing biological tissue mechanics
  2. Novel microstructure-based constitutive model for biological tissues
  3. Growth, remodeling and repair in biological tissues
  4. Quantification of in vivo functional biomechanical properties of biological tissues
  5. Investigations of interrelationship of tissue’s biomechanical behavior to its underlying microstructure
  6. Verification, validation and uncertainty quantification in image-based patient-specific simulations
  7. Advanced computational biomechanics, such as reduced-order modeling, for fast personalized surgery simulations and pre-operative treatment planning
  8. Molecular and cellular biomechanics informed tissue biomechanics

All research areas considered relevant as long as experimentations and/or predictive simulations are the main study drivers.

Dr. Chung-Hao Lee
Dr. Jun Liao
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Bioengineering is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • in vivo stresses/strains
  • constitutive models
  • growth and remodeling (G&R)
  • multiscale biomechanics
  • patient-specific modeling

Published Papers (12 papers)

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Research

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Open AccessArticle
A Pilot Study on Linking Tissue Mechanics with Load-Dependent Collagen Microstructures in Porcine Tricuspid Valve Leaflets
Bioengineering 2020, 7(2), 60; https://doi.org/10.3390/bioengineering7020060 - 18 Jun 2020
Abstract
The tricuspid valve (TV) is composed of three leaflets that coapt during systole to prevent deoxygenated blood from re-entering the right atrium. The connection between the TV leaflets’ microstructure and the tissue-level mechanical responses has yet to be fully understood in the TV [...] Read more.
The tricuspid valve (TV) is composed of three leaflets that coapt during systole to prevent deoxygenated blood from re-entering the right atrium. The connection between the TV leaflets’ microstructure and the tissue-level mechanical responses has yet to be fully understood in the TV biomechanics society. This pilot study sought to examine the load-dependent collagen fiber architecture of the three TV leaflets, by employing a multiscale, combined experimental approach that utilizes tissue-level biaxial mechanical characterizations, micro-level collagen fiber quantification, and histological analysis. Our results showed that the three TV leaflets displayed greater extensibility in the tissues’ radial direction than in the circumferential direction, consistently under different applied biaxial tensions. Additionally, collagen fibers reoriented towards the direction of the larger applied load, with the largest changes in the alignment of the collagen fibers under radially-dominant loading. Moreover, collagen fibers in the belly region of the TV leaflets were found to experience greater reorientations compared to the tissue region closer to the TV annulus. Furthermore, histological examinations of the TV leaflets displayed significant regional variation in constituent mass fraction, highlighting the heterogeneous collagen microstructure. The combined experimental approach presented in this work enables the connection of tissue mechanics, collagen fiber microstructure, and morphology for the TV leaflets. This experimental methodology also provides a new research platform for future developments, such as multiscale models for the TVs, and the design of bioprosthetic heart valves that could better mimic the mechanical, microstructural, and morphological characteristics of the native tricuspid valve leaflets. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessArticle
Effect of Residual and Transformation Choice on Computational Aspects of Biomechanical Parameter Estimation of Soft Tissues
Bioengineering 2019, 6(4), 100; https://doi.org/10.3390/bioengineering6040100 - 29 Oct 2019
Abstract
Several nonlinear and anisotropic constitutive models have been proposed to describe the biomechanical properties of soft tissues, and reliably estimating the unknown parameters in these models using experimental data is an important step towards developing predictive capabilities. However, the effect of parameter estimation [...] Read more.
Several nonlinear and anisotropic constitutive models have been proposed to describe the biomechanical properties of soft tissues, and reliably estimating the unknown parameters in these models using experimental data is an important step towards developing predictive capabilities. However, the effect of parameter estimation technique on the resulting biomechanical parameters remains under-analyzed. Standard off-the-shelf techniques can produce unreliable results where the parameters are not uniquely identified and can vary with the initial guess. In this study, a thorough analysis of parameter estimation techniques on the resulting properties for four multi-parameter invariant-based constitutive models is presented. It was found that linear transformations have no effect on parameter estimation for the presented cases, and nonlinear transforms are necessary for any improvement. A distinct focus is put on the issue of non-convergence, and we propose simple modifications that not only improve the speed of convergence but also avoid convergence to a wrong solution. The proposed modifications are straightforward to implement and can avoid severe problems in the biomechanical analysis. The results also show that including the fiber angle as an unknown in the parameter estimation makes it extremely challenging, where almost all of the formulations and models fail to converge to the true solution. Therefore, until this issue is resolved, a non-mechanical—such as optical—technique for determining the fiber angle is required in conjunction with the planar biaxial test for a robust biomechanical analysis. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessCommunication
Mechanical Response Changes in Porcine Tricuspid Valve Anterior Leaflet Under Osmotic-Induced Swelling
Bioengineering 2019, 6(3), 70; https://doi.org/10.3390/bioengineering6030070 - 15 Aug 2019
Cited by 1
Abstract
Since many soft tissues function in an isotonic in-vivo environment, it is expected that physiological osmolarity will be maintained when conducting experiments on these tissues ex-vivo. In this study, we aimed to examine how not adhering to such a practice may alter the [...] Read more.
Since many soft tissues function in an isotonic in-vivo environment, it is expected that physiological osmolarity will be maintained when conducting experiments on these tissues ex-vivo. In this study, we aimed to examine how not adhering to such a practice may alter the mechanical response of the tricuspid valve (TV) anterior leaflet. Tissue specimens were immersed in deionized (DI) water prior to quantification of the stress–strain responses using an in-plane biaxial mechanical testing device. Following a two-hour immersion in DI water, the tissue thickness increased an average of 107.3% in the DI water group compared to only 6.8% in the control group, in which the tissue samples were submerged in an isotonic phosphate buffered saline solution for the same period of time. Tissue strains evaluated at 85 kPa revealed a significant reduction in the radial direction, from 34.8% to 20%, following immersion in DI water. However, no significant change was observed in the control group. Our study demonstrated the impact of a hypo-osmotic environment on the mechanical response of TV anterior leaflet. The imbalance in ions leads to water absorption in the valvular tissue that can alter its mechanical response. As such, in ex-vivo experiments for which the native mechanical response of the valves is important, using an isotonic buffer solution is essential. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessArticle
Biomechanical Restoration Potential of Pentagalloyl Glucose after Arterial Extracellular Matrix Degeneration
Bioengineering 2019, 6(3), 58; https://doi.org/10.3390/bioengineering6030058 - 03 Jul 2019
Cited by 1
Abstract
The objective of this study was to quantify pentagalloyl glucose (PGG) mediated biomechanical restoration of degenerated extracellular matrix (ECM). Planar biaxial tensile testing was performed for native (N), enzyme-treated (collagenase and elastase) (E), and PGG (P) treated porcine abdominal aorta specimens (n = [...] Read more.
The objective of this study was to quantify pentagalloyl glucose (PGG) mediated biomechanical restoration of degenerated extracellular matrix (ECM). Planar biaxial tensile testing was performed for native (N), enzyme-treated (collagenase and elastase) (E), and PGG (P) treated porcine abdominal aorta specimens (n = 6 per group). An Ogden material model was fitted to the stress–strain data and finite element computational analyses of simulated native aorta and aneurysmal abdominal aorta were performed. The maximum tensile stress of the N group was higher than that in both E and P groups for both circumferential (43.78 ± 14.18 kPa vs. 10.03 ± 2.68 kPa vs. 13.85 ± 3.02 kPa; p = 0.0226) and longitudinal directions (33.89 ± 8.98 kPa vs. 9.04 ± 2.68 kPa vs. 14.69 ± 5.88 kPa; p = 0.0441). Tensile moduli in the circumferential direction was found to be in descending order as N > P > E (195.6 ± 58.72 kPa > 81.8 ± 22.76 kPa > 46.51 ± 15.04 kPa; p = 0.0314), whereas no significant differences were found in the longitudinal direction (p = 0.1607). PGG binds to the hydrophobic core of arterial tissues and the crosslinking of ECM fibers is one of the possible explanations for the recovery of biomechanical properties observed in this study. PGG is a beneficial polyphenol that can be potentially translated to clinical practice for preventing rupture of the aneurysmal arterial wall. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessArticle
Mechanical Response of Porcine Liver Tissue under High Strain Rate Compression
Bioengineering 2019, 6(2), 49; https://doi.org/10.3390/bioengineering6020049 - 30 May 2019
Abstract
In automobile accidents, abdominal injuries are often life-threatening yet not apparent at the time of initial injury. The liver is the most commonly injured abdominal organ from this type of trauma. In contrast to current safety tests involving crash dummies, a more detailed, [...] Read more.
In automobile accidents, abdominal injuries are often life-threatening yet not apparent at the time of initial injury. The liver is the most commonly injured abdominal organ from this type of trauma. In contrast to current safety tests involving crash dummies, a more detailed, efficient approach to predict the risk of human injuries is computational modelling and simulations. Further, the development of accurate computational human models requires knowledge of the mechanical properties of tissues in various stress states, especially in high-impact scenarios. In this study, a polymeric split-Hopkinson pressure bar (PSHPB) was utilized to apply various high strain rates to porcine liver tissue to investigate its material behavior during high strain rate compression. Liver tissues were subjected to high strain rate impacts at 350, 550, 1000, and 1550 s−1. Tissue directional dependency was also explored by PSHPB testing along three orthogonal directions of liver at a strain rate of 350 s−1. Histology of samples from each of the three directions was performed to examine the structural properties of porcine liver. Porcine liver tissue showed an inelastic and strain rate-sensitive response at high strain rates. The liver tissue was found lacking directional dependency, which could be explained by the isotropic microstructure observed after staining and imaging. Furthermore, finite element analysis (FEA) of the PSHPB tests revealed the stress profile inside liver tissue and served as a validation of PSHPB methodology. The present findings can assist in the development of more accurate computational models of liver tissue at high-rate impact conditions allowing for understanding of subfailure and failure mechanisms. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessArticle
Tissue Level Mechanical Properties and Extracellular Matrix Investigation of the Bovine Jugular Venous Valve Tissue
Bioengineering 2019, 6(2), 45; https://doi.org/10.3390/bioengineering6020045 - 14 May 2019
Abstract
Jugular venous valve incompetence has no long-term remedy and symptoms of transient global amnesia and/or intracranial hypertension continue to discomfort patients. During this study, we interrogate the synergy of the collagen and elastin microstructure that compose the bi-layer extracellular matrix (ECM) of the [...] Read more.
Jugular venous valve incompetence has no long-term remedy and symptoms of transient global amnesia and/or intracranial hypertension continue to discomfort patients. During this study, we interrogate the synergy of the collagen and elastin microstructure that compose the bi-layer extracellular matrix (ECM) of the jugular venous valve. In this study, we investigate the jugular venous valve and relate it to tissue-level mechanical properties, fibril orientation and fibril composition to improve fundamental knowledge of the jugular venous valves toward the development of bioprosthetic venous valve replacements. Steps include: (1) multi loading biaxial mechanical tests; (2) isolation of the elastin microstructure; (3) imaging of the elastin microstructure; and (4) imaging of the collagen microstructure, including an experimental analysis of crimp. Results from this study show that, during a 3:1 loading ratio (circumferential direction: 900 mN and radial direction: 300 mN), elastin may have the ability to contribute to the circumferential mechanical properties at low strains, for example, shifting the inflection point toward lower strains in comparison to other loading ratios. After isolating the elastin microstructure, light microscopy revealed that the overall elastin orients in the radial direction while forming a crosslinked mesh. Collagen fibers were found undulated, aligning in parallel with neighboring fibers and orienting in the circumferential direction with an interquartile range of −10.38° to 7.58° from the circumferential axis (n = 20). Collagen crimp wavelength and amplitude was found to be 38.46 ± 8.06 µm and 4.51 ± 1.65 µm, respectively (n = 87). Analyzing collagen crimp shows that crimp permits about 12% true strain circumferentially, while straightening of the overall fibers accounts for more. To the best of the authors’ knowledge, this is the first study of the jugular venous valve linking the composition and orientation of the ECM to its mechanical properties and this study will aid in forming a structure-based constitutive model. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessArticle
Compressive Mechanical Properties of Porcine Brain: Experimentation and Modeling of the Tissue Hydration Effects
Bioengineering 2019, 6(2), 40; https://doi.org/10.3390/bioengineering6020040 - 07 May 2019
Abstract
Designing protective systems for the human head—and, hence, the brain—requires understanding the brain’s microstructural response to mechanical insults. We present the behavior of wet and dry porcine brain undergoing quasi-static and high strain rate mechanical deformations to unravel the effect of hydration on [...] Read more.
Designing protective systems for the human head—and, hence, the brain—requires understanding the brain’s microstructural response to mechanical insults. We present the behavior of wet and dry porcine brain undergoing quasi-static and high strain rate mechanical deformations to unravel the effect of hydration on the brain’s biomechanics. Here, native ‘wet’ brain samples contained ~80% (mass/mass) water content and ‘dry’ brain samples contained ~0% (mass/mass) water content. First, the wet brain incurred a large initial peak stress that was not exhibited by the dry brain. Second, stress levels for the dry brain were greater than the wet brain. Third, the dry brain stress–strain behavior was characteristic of ductile materials with a yield point and work hardening; however, the wet brain showed a typical concave inflection that is often manifested by polymers. Finally, finite element analysis (FEA) of the brain’s high strain rate response for samples with various proportions of water and dry brain showed that water played a major role in the initial hardening trend. Therefore, hydration level plays a key role in brain tissue micromechanics, and the incorporation of this hydration effect on the brain’s mechanical response in simulated injury scenarios or virtual human-centric protective headgear design is essential. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessArticle
Elastin-Dependent Aortic Heart Valve Leaflet Curvature Changes During Cyclic Flexure
Bioengineering 2019, 6(2), 39; https://doi.org/10.3390/bioengineering6020039 - 07 May 2019
Abstract
The progression of calcific aortic valve disease (CAVD) is characterized by extracellular matrix (ECM) remodeling, leading to structural abnormalities and improper valve function. The focus of the present study was to relate aortic valve leaflet axial curvature changes as a function of elastin [...] Read more.
The progression of calcific aortic valve disease (CAVD) is characterized by extracellular matrix (ECM) remodeling, leading to structural abnormalities and improper valve function. The focus of the present study was to relate aortic valve leaflet axial curvature changes as a function of elastin degradation, which has been associated with CAVD. Circumferential rectangular strips (L × W = 10 × 2.5 mm) of normal and elastin-degraded (via enzymatic digestion) porcine AV leaflets were subjected to cyclic flexure (1 Hz). A significant increase in mean curvature (p < 0.05) was found in elastin-degraded leaflet specimens in comparison to un-degraded controls at both the semi-constrained (50% of maximum flexed state during specimen bending and straightening events) and fully-constrained (maximally-flexed) states. This significance did not occur in all three flexed configurations when measurements were performed using either minimum or maximum curvature. Moreover, the mean curvature increase in the elastin-degraded leaflets was most pronounced at the instance of maximum flexure, compared to un-degraded controls. We conclude that the mean axial curvature metric can detect distinct spatial changes in aortic valve ECM arising from the loss in bulk content and/or structure of elastin, particularly when there is a high degree of tissue bending. Therefore, the instance of maximum leaflet flexure during the cardiac cycle could be targeted for mean curvature measurements and serve as a potential biomarker for elastin degradation in early CAVD remodeling. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessArticle
Adverse Hemodynamic Conditions Associated with Mechanical Heart Valve Leaflet Immobility
Bioengineering 2018, 5(3), 74; https://doi.org/10.3390/bioengineering5030074 - 16 Sep 2018
Cited by 11
Abstract
Artificial heart valves may dysfunction, leading to thrombus and/or pannus formations. Computational fluid dynamics is a promising tool for improved understanding of heart valve hemodynamics that quantify detailed flow velocities and turbulent stresses to complement Doppler measurements. This combined information can assist in [...] Read more.
Artificial heart valves may dysfunction, leading to thrombus and/or pannus formations. Computational fluid dynamics is a promising tool for improved understanding of heart valve hemodynamics that quantify detailed flow velocities and turbulent stresses to complement Doppler measurements. This combined information can assist in choosing optimal prosthesis for individual patients, aiding in the development of improved valve designs, and illuminating subtle changes to help guide more timely early intervention of valve dysfunction. In this computational study, flow characteristics around a bileaflet mechanical heart valve were investigated. The study focused on the hemodynamic effects of leaflet immobility, specifically, where one leaflet does not fully open. Results showed that leaflet immobility increased the principal turbulent stresses (up to 400%), and increased forces and moments on both leaflets (up to 600% and 4000%, respectively). These unfavorable conditions elevate the risk of blood cell damage and platelet activation, which are known to cascade to more severe leaflet dysfunction. Leaflet immobility appeared to cause maximal velocity within the lateral orifices. This points to the possible importance of measuring maximal velocity at the lateral orifices by Doppler ultrasound (in addition to the central orifice, which is current practice) to determine accurate pressure gradients as markers of valve dysfunction. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Review

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Open AccessReview
Mechanics and Microstructure of the Atrioventricular Heart Valve Chordae Tendineae: A Review
Bioengineering 2020, 7(1), 25; https://doi.org/10.3390/bioengineering7010025 - 12 Mar 2020
Abstract
The atrioventricular heart valves (AHVs) are responsible for directing unidirectional blood flow through the heart by properly opening and closing the valve leaflets, which are supported in their function by the chordae tendineae and the papillary muscles. Specifically, the chordae tendineae are critical [...] Read more.
The atrioventricular heart valves (AHVs) are responsible for directing unidirectional blood flow through the heart by properly opening and closing the valve leaflets, which are supported in their function by the chordae tendineae and the papillary muscles. Specifically, the chordae tendineae are critical to distributing forces during systolic closure from the leaflets to the papillary muscles, preventing leaflet prolapse and consequent regurgitation. Current therapies for chordae failure have issues of disease recurrence or suboptimal treatment outcomes. To improve those therapies, researchers have sought to better understand the mechanics and microstructure of the chordae tendineae of the AHVs. The intricate structures of the chordae tendineae have become of increasing interest in recent literature, and there are several key findings that have not been comprehensively summarized in one review. Therefore, in this review paper, we will provide a summary of the current state of biomechanical and microstructural characterizations of the chordae tendineae, and also discuss perspectives for future studies that will aid in a better understanding of the tissue mechanics–microstructure linking of the AHVs’ chordae tendineae, and thereby improve the therapeutics for heart valve diseases caused by chordae failures. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessReview
Current Understanding of the Biomechanics of Ventricular Tissues in Heart Failure
Bioengineering 2020, 7(1), 2; https://doi.org/10.3390/bioengineering7010002 - 20 Dec 2019
Cited by 1
Abstract
Heart failure is the leading cause of death worldwide, and the most common cause of heart failure is ventricular dysfunction. It is well known that the ventricles are anisotropic and viscoelastic tissues and their mechanical properties change in diseased states. The tissue mechanical [...] Read more.
Heart failure is the leading cause of death worldwide, and the most common cause of heart failure is ventricular dysfunction. It is well known that the ventricles are anisotropic and viscoelastic tissues and their mechanical properties change in diseased states. The tissue mechanical behavior is an important determinant of the function of ventricles. The aim of this paper is to review the current understanding of the biomechanics of ventricular tissues as well as the clinical significance. We present the common methods of the mechanical measurement of ventricles, the known ventricular mechanical properties including the viscoelasticity of the tissue, the existing computational models, and the clinical relevance of the ventricular mechanical properties. Lastly, we suggest some future research directions to elucidate the roles of the ventricular biomechanics in the ventricular dysfunction to inspire new therapies for heart failure patients. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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Open AccessReview
Mechanics of the Tricuspid Valve—From Clinical Diagnosis/Treatment, In-Vivo and In-Vitro Investigations, to Patient-Specific Biomechanical Modeling
Bioengineering 2019, 6(2), 47; https://doi.org/10.3390/bioengineering6020047 - 22 May 2019
Cited by 11
Abstract
Proper tricuspid valve (TV) function is essential to unidirectional blood flow through the right side of the heart. Alterations to the tricuspid valvular components, such as the TV annulus, may lead to functional tricuspid regurgitation (FTR), where the valve is unable to prevent [...] Read more.
Proper tricuspid valve (TV) function is essential to unidirectional blood flow through the right side of the heart. Alterations to the tricuspid valvular components, such as the TV annulus, may lead to functional tricuspid regurgitation (FTR), where the valve is unable to prevent undesired backflow of blood from the right ventricle into the right atrium during systole. Various treatment options are currently available for FTR; however, research for the tricuspid heart valve, functional tricuspid regurgitation, and the relevant treatment methodologies are limited due to the pervasive expectation among cardiac surgeons and cardiologists that FTR will naturally regress after repair of left-sided heart valve lesions. Recent studies have focused on (i) understanding the function of the TV and the initiation or progression of FTR using both in-vivo and in-vitro methods, (ii) quantifying the biomechanical properties of the tricuspid valve apparatus as well as its surrounding heart tissue, and (iii) performing computational modeling of the TV to provide new insight into its biomechanical and physiological function. This review paper focuses on these advances and summarizes recent research relevant to the TV within the scope of FTR. Moreover, this review also provides future perspectives and extensions critical to enhancing the current understanding of the functioning and remodeling tricuspid valve in both the healthy and pathophysiological states. Full article
(This article belongs to the Special Issue Advances in Biological Tissue Biomechanics)
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