Gross morphology and morphometry of native and decellularized heart valves of caprine: A comparative study.

The gross morphological examination of native caprine heart valves revealed distinctive structural characteristics of the caprine's cardiac anatomy. Four primary orifices were identified, each protected by thin, valve-like structures. Atrioventricular orifices featured tricuspid and bicuspid valves, while the aorta and pulmonary arteries were guarded by semilunar valves. Within the atrioventricular apparatus, distinct features were observed including the tricuspid valve's three leaflets and the bicuspid valve's anterior and posterior leaflets. Ultrasonography provided insights into valve thickness and chordae tendineae lengths. Morphometric studies compared leaflets/cusps within individual native valves, showcasing significant variations in dimensions. Comparative analysis between native and decellularized valves highlighted the effects of decellularization on leaflet thickness and chordae tendineae lengths. Decellularized valves exhibited reduced dimensions compared to native valves, indicating successful removal of cellular components. While some dimensions remained unchanged post-decellularization, significant reductions were observed in leaflet thicknesses and chordae tendineae lengths. Notably, semilunar valve cusps displayed varying responses to decellularization, with significant reductions in cusp lengths observed in the aortic valve, while the pulmonary valve exhibited more subtle changes. These findings underscore the importance of understanding structural alterations in heart valves post-decellularization, providing valuable insights for tissue engineering applications and regenerative medicine.

Peculiarities in coronary sinus anatomy: implications for successful cannulation from an autoptic study.

AIMS: The number of cardiovascular procedures using the coronary sinus (CS) as a gateway is constantly increasing. The present study aimed to define specific structures within CS, which could potentially complicate CS cannulation and to develop a new Thebesian valve (TV) classification system. METHODS AND RESULTS: The study was performed on 560 consecutive unfixed cadaveric hearts during routine autopsy examination (1-3 days post-mortem). Basic CS dimensions were measured and the presence and dimensions of the TV and the Vieussens valve (VV) were assessed. Thebesian valves were classified according to their morphology into six main types: remnant fold, semilunar, fenestrated, chord, fused strands, and mixed shaped. The median age of hearts was 48 years (range 16-95 years), and 38.9% were female. Thebesian valve was present in 79.5%. The most common TV type was semilunar (54%) followed by fenestrated (8.2%), remnant fold (5.5%), fused strands (4.8%), chord (4.0%), and mixed shaped (3.0%). In 1.1% of hearts, TV totally covered the coronary sinus ostium (CSO). The VV was detected in 67.9%. Potentially occlusive VV was found in 1.1% hearts and in all of which it coexisted with obstructive TV. The median CSO area was 87.9 mm2 [interquartile range (IQR): 56.5-127.1 mm2] and median CS length was 38 mm (IQR: 29.5-45 mm). The CSO area and CS length correlated with each other and with the right atrium's dimensions. CONCLUSION: We identified six types of TVs, among which only 1.1% TVs caused total occlusion of CSO. The obstructive TV co-existed with potentially occlusive VV what might hinder CS cannulation.

Structural remodelling of the heart valves extracellular matrix during embryo development.

Alterations in heart valve development represent more than 20% of congenital cardiovascular malformations. Most of the functional properties of heart valves depend on extracellular matrix. Despite its relevance, little is known about fibrillar components on developing stages. Our objective is to define histological changes on valves fibrillar components in late embryonic development of Mus musculus. We found type III collagen as the predominant fibre type in the ECM in prenatal stages followed by a switch to a type I predominance for postnatal ages. The change in fibrillar components is necessary to support the normal mechanical function of adult heart valves.

Leaflet Tissue Generation from Microfibrous Heart Valve Leaflet Scaffolds with Native Characteristics.

Mechanical and bioprosthetic valves that are currently applied for replacing diseased heart valves are not fully efficient. Heart valve tissue engineering may solve the issues faced by the prosthetic valves in heart valve replacement. The leaflets of native heart valves have a trilayered structure with layer-specific orientations; thus, it is imperative to develop functional leaflet tissue constructs with a native trilayered, oriented structure. Its key solution is to develop leaflet scaffolds with a native morphology and structure. In this study, microfibrous leaflet scaffolds with a native trilayered and oriented structure were developed in an electrospinning system. The scaffolds were implanted for 3 months in rats subcutaneously to study the scaffold efficiencies in generating functional tissue-engineered leaflet constructs. These in vivo tissue-engineered leaflet constructs had a trilayered, oriented structure similar to native leaflets. The tensile properties of constructs indicated that they were able to endure the hydrodynamic load of the native heart valve. Collagen, glycosaminoglycans, and elastin─the predominant extracellular matrix components of native leaflets─were found sufficiently in the leaflet tissue constructs. The residing cells in the leaflet tissue constructs showed vimentin and α-smooth muscle actin expression, i.e., the constructs were in a growing state. Thus, the trilayered, oriented fibrous leaflet scaffolds produced in this study could be useful to develop heart valve scaffolds for successful heart valve replacements.

Image analysis of morphometric evaluation from the heart valves for age estimation in Thai population / Análisis de la evaluación morfométrica de las valvas cardíacas para la estimación de la edad en la población tailandesa

Determination of age represents one of the most important aspects in forensic identification. Through aging, changes can occur in morphological structures of the heart valves. The objective is to examine the relationship between the dimensions of the rigth atrioventricular (tricuspid), pulmonary, left atrioventricular (mitral), and aortic valves and age at death. Sixty fresh human hearts were obtained from Department of Anatomy and Department of Forensic Medicine, Faculty of medicine, Chiang Mai University, Thailand. The age of individuals was between 20-90 years. We investigated the morphometric parameters of the valves were taken including: valve circumference, length, the height and area of each leaflet. All parameters were measured by using specific image analysis software. The correlation test and predictive equation were established. The positive correlation between the circumference, area of posterior leaflet, height of anterior leaflet, and area of anterior leaflet of the rigth atrioventricular valve were found. The left atrioventricular valve showed correlation with age in circumference, length and area of posterior leaflet. For the pulmonary and aortic valves, there were correlated between circumference at sinotubular junction and leaflet sizes in almost leaflets. The circumference at sinotubular junction of the pulmonary valve was highest significantly correlation with age (r=0.693). The predictive equation was age = -3.659+0.652(Circumference at sinotubular junction of the pulmonary valve) with standard error of ± 14.7 years. Additional knowledge of morphometric features in human heart valves and its relationship with age could be used as age indicator in forensic field.

La determinación de la edad representa uno de los aspectos más importantes en la identificación forense. Pueden ocurrir cambios a través del envejecimiento, en las estructuras morfológicas de las válvulas cardíacas. El objetivo de este estudio fue examinar la relación entre las dimensiones de las valvas atrioventricular derecha (tricúspide), pulmonar, atrioventricular izquierda (mitral) y aórtica, y la edad en relación a la muerte. Se obtuvieron sesenta corazones humanos frescos del Departamento de Anatomía y el Departamento de Medicina Forense de la Facultad de Medicina de la Universidad de Chiang Mai, Tailandia. La edad de las personas fluctuaba entre los 20 y 90 años. Investigamos los parámetros morfométricos de las valvas analizadas, incluyendo: circunferencia de la valva, longitud, altura y área de cada valva. Todos los parámetros se midieron utilizando un software de análisis de imagen específico. Se estableció la prueba de correlación y la ecuación predictiva. Se encontró la correlación positiva entre la circunferencia, el área de la valvula posterior, la altura de la valvula anterior y el área de la valvula anterior de la valva atrioventricular derecha. La valva atrioventricular izquierda mostró correlación con la edad en la circunferencia, longitud y área de la valvula posterior. Para las valvas pulmonar y aórtica, se correlacionó entre la circunferencia en la unión sinotubular y el tamaño de las válvulas. La circunferencia en la unión sinotubular de la valva pulmonar fue la mayor correlación significativa con la edad (r = 0,693). La ecuación predictiva fue edad = -3,659 + 0,652 (circunferencia en la unión sinotubular de la valva pulmonar) con error estándar de ± 14,7 años. El conocimiento adicional de las características morfométricas en las valvas cardíacas humanas y su relación con la edad podría usarse como indicador de edad en el campo forense.

Morphometry and topography of the coronary ostia in the European bison.

BACKGROUND: Coronary vessels have been widely studied in many species of domestic and wild mammals. However, there are no available literature reports describing the morphology and morphometry of the coronary ostia of the European bison (Bison bonasus). The aim of this study was to measure the area of the coronary ostia and assess their localisation in the coronary sinuses of the aortic root in the European bison. MATERIALS AND METHODS: The study material comprised 27 hearts from European bison of both sexes (16 males and 11 females), from 3 months to 26 years old, inhabiting the Bialowieza Forest (Bialowieza National Park, Poland). The animals were divided into two age groups: ≤ 5 years (group I) and > 5 years (group II). RESULTS: In all the studied European bison, the aortic valve consisted of three semilunar leaflets, left, right and septal. The ostia of both coronary arteries were located beneath the sinotubular junction. The dimensions of the left coronary ostium were larger than those of the right coronary ostium. They were longer by on average 4.5 mm (95% confidence interval [CI] 3.5-5.6 mm), they were wider by on average 1.6 mm (95% CI 1.0-2.2 mm) and they had a larger area by on average 31.6 mm2 (95% CI 22.7-40.5 mm2). This was evident both in young and in adult bison. After adjusting for age, there were no differences in the ostia dimensions between males and females. There were no differences in the structure of the left and right coronary arteries in nine animals. In the remaining 18 animals, there were variations in the morphology of the coronary ostia or additional ostia. CONCLUSIONS: Because of the anatomical similarity between the European bison and other ruminants, the results of this study can be applied to the other species including endangered ones.

Trilayered tissue structure with leaflet-like orientations developed through in vivo tissue engineering.

A tissue-engineered heart valve can be an alternative to current mechanical or bioprosthetic valves that face limitations, especially in pediatric patients. However, it remains challenging to produce a functional tissue-engineered heart valve with three leaflets mimicking the trilayered, oriented structure of a native valve leaflet. In our previous study, a flat, trilayered nanofibrous substrate mimicking the orientations of three layers in a native leaflet-circumferential, random and radial orientations in fibrosa, spongiosa and ventricularis layers, respectively, was developed through electrospinning. In this study, we sought to develop a trilayered tissue structure mimicking the orientations of a native valve leaflet through in vivo tissue engineering, a practical regenerative medicine technology that can be used to develop an autologous heart valve. Thus, the nanofibrous substrate was placed inside the closed trileaflet-shaped cavity of a mold and implanted subcutaneously in a rat model for in vivo tissue engineering. After two months, the explanted tissue construct had a trilayered structure mimicking the orientations of a native valve leaflet. The infiltrated cells and their deposited collagen fibrils were oriented along the nanofibers in each layer of the substrate. Besides collagen, presence of glycosaminoglycans and elastin in the construct was observed.

Testing Species Assignments in Extant Terebratulide Brachiopods: A Three-dimensional Geometric Morphometric Analysis of Long-Looped Brachidia.

Species of terebratulide brachiopods have been largely characterized qualitatively on the basis of morphology. Furthermore, species-level morphological variability has rarely been analyzed within a quantitative framework. The objective of our research is to quantify morphological variation to test the validity of extant named species of terebratulide brachiopods, focusing on the lophophore-supporting structures-the "long loops." Long loops are the most distinctive and complex morphological feature in terebratellidine brachiopods and are considered to be phylogenetically and taxonomically informative. We studied eight species with problematic species identities in three genera distributed in the North Pacific: Laqueus, Terebratalia, and Dallinella. Given how geometrically complex long loops are, we generated 3D models from computed tomography (CT) scans of specimens of these eight species and analyzed them using 3D geometric morphometrics. Our goal was to determine ranges of variation and to test whether species are clearly distinguishable from one another in morphospace and statistically. Previous studies have suggested that some species might be overly split and are indistinguishable. Our results show that these extant species of terebratellidines can be reliably distinguished on the basis of quantitative loop morphometrics. Using 3D geometric morphometric methods, we demonstrate the utility of CT beyond purely descriptive imaging purposes in testing the morphometric validity of named species. It is crucial to treat species described and named from qualitative morphology as working hypotheses to be tested; many macroevolutionary studies depend upon the accurate assessment of species in order to identify and seek to explain macroevolutionary patterns. Our results provide quantitative documentation of the distinction of these species and thus engender greater confidence in their use to characterize macroevolutionary patterns among extant terebratellidine brachiopods. These methods, however, require further testing in extinct terebratellidines, which only rarely preserve the delicate long loop in three dimensions. In addition, molecular analyses of extant terebratellidines will test the species delimitations supported by the morphometric analyses presented in this study. [Species determination; morphological variability; 3D geometric morphometrics; terebratulide brachiopods; long loops.].

Valves of the small coronary veins in porcine hearts.

The aim of the study was to investigate the existence of valves in small peripheral coronary veins of porcine hearts. The study was performed on 20 porcine hearts using standard histological methods. The veins in the subepicardial and intramyocardial regions of the anterior and posterior parts of the interventricular septum and in the wall of the right atrium were studied. Valves were present in intramyocardial veins (diameter of 75-180 µm), in the veins located just beneath the external surface of the myocardium (diameter 120-170 µm) and in the terminal segments of the ventricular veins (diameter 250 µm) opening into the stems of the anterior interventricular vein and middle cardiac vein. Valves were also recorded in most veins of the subepicardial space. The described rich presence of valves in the small coronary veins may contribute to a better comprehension of their hemodynamic properties. These findings may also help to improve the understanding of the efficacy of retrograde application of medications, a novel technique in cardiology and cardiac surgery.

The valves of the cardiac outflow tract of the starry ray, Raja asterias (Chondrichthyes; Rajiformes): Anatomical, histological and evolutionary aspects.

The cardiac outflow tract of chondrichthyans is composed of the myocardial conus arteriosus, equipped with valves at its luminal side, and the bulbus arteriosus devoid of myocardium. Knowledge of the histomorphology of the conal valves is scarce despite their importance in preventing blood backflow to the heart. Current information on the subject refers to a single shark species. The present report is the first to describe the structure of the conal valves of a batoid species, namely, Raja asterias. Hearts from seven starry rays were examined using scanning electron microscopy and histochemical techniques for light microscopy. In all hearts, the conus showed four transverse rows of three pocket-like valves each. Each valve was composed of a leaflet and its supporting sinus. The leaflet had a stout central body, rich in glycosaminoglycans, which contained fibroblasts, collagen and elastin. The central body was surrounded by two thin fibrous layers, outer and inner, formed mainly by collagen. The valves of the anterior row, which were the largest of the valvular system, were attached proximally to the conus arteriosus and distally to the bulbus arteriosus, and not to the ventral aorta as previously reported for chondrichthyans. The arrangement of the anterior valves in the starry ray is an anatomical pattern that apparently has been preserved throughout the evolution of vertebrates.

Behavior of valvular interstitial cells on trilayered nanofibrous substrate mimicking morphologies of heart valve leaflet.

Heart valve tissue engineering could be an alternative to the current bioprosthetic heart valve that faces limitations especially in pediatric patients. However, heart valve tissue engineering has remained challenging because leaflets - the primary component of a heart valve - have three layers with three diverse orientations - circumferential, random and radial, respectively. In order to mimic the orientations, we first designed three novel collectors to fabricate three nanofibrous layers with those orientations from a polymeric biomaterial in an electrospinning system. Then, we devised a novel direct electrospinning technique to develop a unified trilayered nanofibrous (TN) substrate comprising those oriented layers. The TN substrate supported the growth and orientations of seeded porcine valvular interstitial cells (PVICs) and their deposited collagen fibrils. After one month culture, the obtained trilayered tissue construct (TC) exhibited increased tensile properties over its TN substrate. Most importantly, the developed TC did not show any sign of shrinkage. Gene expression pattern of the PVICs indicated the developing stage of the TC. Their protein expression pattern was quite similar to that of leaflets. STATEMENT OF SIGNIFICANCE: This manuscript talks about development of a novel trilayered nanofibrous substrate mimicking the morphologies of a heart valve leaflet. It also describes culturing of valvular interstitial cells that reside in a leaflet, in the substrate and compares the behavior of the cultured cells with that in native leaflets in terms cell morphology, protein deposition and its orientation, and molecular signature. This study builds the groundwork for our future trilayered, tissue-engineered leaflet development. This research article would be of great interest to investigators and researchers in the field of cardiovascular tissue engineering especially in cardiac valve tissue engineering through biomaterial-based tissue engineering.

An investigation of the anisotropic mechanical properties and anatomical structure of porcine atrioventricular heart valves.

Valvular heart diseases are complex disorders, varying in pathophysiological mechanism and affected valve components. Understanding the effects of these diseases on valve functionality requires a thorough characterization of the mechanics and structure of the healthy heart valves. In this study, we performed biaxial mechanical experiments with extensive testing protocols to examine the mechanical behaviors of the mitral valve and tricuspid valve leaflets. We also investigated the effect of loading rate, testing temperatures, species (porcine versus ovine hearts), and age (juvenile vs adult ovine hearts) on the mechanical responses of the leaflet tissues. In addition, we evaluated the structure of chordae tendineae within each valve and performed histological analysis on each atrioventricular leaflet. We found all tissues displayed a characteristic nonlinear anisotropic mechanical response, with radial stretches on average 30.7% higher than circumferential stretches under equibiaxial physiological loading. Tissue mechanical responses showed consistent mechanical stiffening in response to increased loading rate and minor temperature dependence in all five atrioventricular heart valve leaflets. Moreover, our anatomical study revealed similar chordae quantities in the porcine mitral (30.5 ±â€¯1.43 chords) and tricuspid valves (35.3 ±â€¯2.45 chords) but significantly more chordae in the porcine than the ovine valves (p < 0.010). Our histological analyses quantified the relative thicknesses of the four distinct morphological layers in each leaflet. This study provides a comprehensive database of the mechanics and structure of the atrioventricular valves, which will be beneficial to development of subject-specific atrioventricular valve constitutive models and toward multi-scale biomechanical investigations of heart valve function to improve valvular disease treatments.

Study on the Accuracy of Structural and FSI Heart Valves Simulations.

PURPOSE: The performance of heart valves, either native or artificial, can be evaluated by means of finite element analyses, either from a structural or a fluid-structure interaction (FSI) point of view. The latter captures the coupling between the valve leaflets and the blood in a more realistic way. The selection of the appropriate finite elements approach for the model is the first and fundamental step to achieve accurate simulations. The aim of this work is to investigate the influence of the type, formulation, size, and shape of the elements in heart valves simulations. METHODS: The effects related to the choice of the finite elements-shell or solid- in structural and FSI simulations were analyzed. In particular, the analysis of grid convergence on both the structure and fluid domains, the influence of the element typology, formulation and damping factor in an idealized three-leaflets valve model loaded with physiological pressure conditions were investigated. RESULTS: Stress values and valve kinematics results confirmed the importance of performing a proper verification process for selecting the most appropriate elements with the optimal accuracy to computational cost ratio. CONCLUSION: In this regard, our results indicate the quadrangular shell with reduced integration and viscous hourglass control to be the best choice to model heart valves. If a solid discretization is required, quadratic hexahedral elements with full integration are also acceptable. Finally, our results show that the damping coefficient needs to be carefully selected in order to smooth out the high frequency modes of the structure without introducing excessive numerical artificial viscosity.

The independence of the infundibular building blocks in the setting of double-outlet right ventricle.

It has long been contentious as to whether the presence of bilateral infundibulums, or conuses, is a prerequisite for the diagnosis of double-outlet right ventricle. As the use of such a criterion would abrogate the so-called "morphological method", which correctly states that one variable entity should not be defined on the basis of another entity that is itself variable, it is now accepted that double outlet can exist in the setting of fibrous continuity between the leaflets of the atrioventricular and arterial valves. Although this debate has now been resolved, there are other contentious areas still requiring clarification in the setting of hearts unified because of the presence of this particular ventriculo-arterial connection - for example, it is questionable whether the channel between the ventricles should be described as a "ventricular septal defect", whereas it is equally arguable that the mere presence of fibrous continuity between the leaflets of the arterial valves does not necessarily place the channel in a doubly committed location. In this review, we describe a series of autopsied hearts in which the anatomical features serve to illuminate these various topics. We then discuss recent findings regarding cardiac development that point to the individuality of the building blocks of the ventricular outflow tracts, specifically the outlet septum, the inner heart curvature, or ventriculo-infundibular fold, and the septomarginal trabeculation, or septal band.

The first descriptions of various anatomical structures and embryological remnants of the heart: A systematic overview.

In the present study a brief overview of the history regarding the development of the knowledge of the macroscopic and microscopic anatomical elements of the heart along with some embryological remnants of the heart has been conducted. The evolution of the awareness as regards the various anatomical and embryonic structures of the heart began from Greek medico-philosophers, such as Hippocrates, Herophilus, Erasistratus and Galen, however, such knowledge was enpowered from the meticulous study of philosophers and physicians until the era of modern anatomy. In specific, the following anatomical and embryological structures are displayed: aortic and pulmonary valve, auricles, bundle of Kent, cardiac nerves, conduction system of the heart, ductus arteriosus, intervenous tubercle of Lower, left atrial oblique vein and ligament of Marshall, limbus of fossa ovalis, mitral and tricuspid valve, nodes or nodules of Arantius, ovale foramen, septomarginal trabecula, sinus of Valsava, small cardiac veins or vessels of Thebesius, tendinous chordae and papillary muscles, tendon of the valve of the inferior vena cava and triangle of Koch, valve of the coronary sinus, valve of the inferior vena cava.

Bridging the gap: Hybrid cardiac echo in the critically ill.

BACKGROUND: Point-of-care ultrasound often includes cardiac ultrasound. It is commonly used to evaluate cardiac function in critically ill patients but lacks the specific quantitative anatomic assessment afforded by standard transthoracic echocardiography (TTE). We developed the Focused Rapid Echocardiographic Examination (FREE), a hybrid between a cardiac ultrasound and TTE that places an emphasis on cardiac function rather than anatomy. We hypothesized that data obtained from FREE correlate well with TTE while providing actionable information for clinical decision making. METHODS: FREE examinations evaluating cardiac function (left ventricular ejection fraction), diastolic dysfunction (including early mitral Doppler flow [E] and early mitral tissue Doppler [E']), right ventricular function, cardiac output, preload (left ventricular internal dimension end diastole), stroke volume, stroke volume variation, inferior vena cava diameter, and inferior vena cava collapse were performed. Patients who underwent both a TTE and FREE on the same day were identified as the cohort, and quantitative measurements were compared. Correlation analyses were performed to assess levels of agreement. RESULTS: A total of 462 FREE examinations were performed, in which 69 patients had both a FREE and TTE. FREE ejection fraction was strongly correlated with TTE (r = 0.89, 95% confidence interval). Left ventricular outflow tract, left ventricular internal dimension end diastole, E, and lateral E' derived from FREE were also strongly correlated with TTE measurements (r = 0.83, r = 0.94, r = 0.77, and r = 0.88, respectively). In 82% of the patients, right ventricular function for FREE was the same as that reported for TTE; pericardial effusion was detected on both examinations in 94% of the cases. No significant valvular anatomy was missed with the FREE examination. CONCLUSION: Functionally rather than anatomically based hybrid ultrasound examinations, like the FREE, facilitate decision making for critically ill patients. The FREE's functional assessment correlates well with TTE measurements and may be of significant clinical value in critically ill patients, especially when used in remote operating environments where resources are limited. LEVEL OF EVIDENCE: Diagnostic test, level III.

Normal Variants in Echocardiography.

Echocardiography is a powerful and convenient tool used routinely in the cardiac evaluation of many patients. Improved resolution and visualization of cardiac anatomy has led to the discovery of many normal variant structures that have no known pathologic consequence. Importantly, these findings may masquerade as pathology prompting unnecessary further evaluation at the expense of anxiety, cost, or potential harm. This review provides an updated and comprehensive collection of normal anatomic variants on both transthoracic and transesophageal imaging.

Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves.

There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation-but more pronounced in aortic valves-the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age.

Biomechanical conditioning of tissue engineered heart valves: Too much of a good thing?

Surgical replacement of dysfunctional valves is the primary option for the treatment of valvular disease and congenital defects. Existing mechanical and bioprosthetic replacement valves are far from ideal, requiring concomitant anticoagulation therapy or having limited durability, thus necessitating further surgical intervention. Heart valve tissue engineering (HVTE) is a promising alternative to existing replacement options, with the potential to synthesize mechanically robust tissue capable of growth, repair, and remodeling. The clinical realization of a bioengineered valve relies on the appropriate combination of cells, biomaterials, and/or bioreactor conditioning. Biomechanical conditioning of valves in vitro promotes differentiation of progenitor cells to tissue-synthesizing myofibroblasts and prepares the construct to withstand the complex hemodynamic environment of the native valve. While this is a crucial step in most HVTE strategies, it also may contribute to fibrosis, the primary limitation of engineered valves, through sustained myofibrogenesis. In this review, we examine the progress of HVTE and the role of mechanical conditioning in the synthesis of mechanically robust tissue, and suggest approaches to achieve myofibroblast quiescence and prevent fibrosis.

Numerical modeling of heart valves using resistive Eulerian surfaces.

The goal of this work is the development and numerical implementation of a mathematical model describing the functioning of heart valves. To couple the pulsatile blood flow with a highly deformable thin structure (the valve's leaflets), a resistive Eulerian surfaces framework is adopted. A lumped-parameter model helps to couple the movement of the leaflets with the blood dynamics. A reduced circulation model describes the systemic hemodynamics and provides a physiological pressure profile at the downstream boundary of the valve. The resulting model is relatively simple to describe for a healthy valve and pathological heart valve functioning while featuring an affordable computational burden. Efficient time and spatial discretizations are considered and implemented. We address in detail the main features of the proposed method, and we report several numerical experiments for both two-dimensional and three-dimensional cases with the aim of illustrating its accuracy. Copyright © 2015 John Wiley & Sons, Ltd.