Heart Valve Tissue Research Articles

MicroCT Imaging of Heart Valve Tissue in Fluid.

Heart valve computational models require high quality geometric input data, commonly obtained using micro-computed tomography. Whether in the open or closed configuration, most studies utilize dry valves, which poses significant challenges including gravitational and surface tension effects along with desiccation induced mechanical changes. These challenges are overcome by scanning in a stress-free configuration in fluid. Utilizing fluid backgrounds however reduces overall contrast due to the similar density of fluid and tissue. The work presented here demonstrates imaging of the mitral valve by utilizing an iodine-based staining solution to improve the contrast of valve tissue against a fluid background and investigates the role of stain time and concentration. It is determined that an Olea europaea oil bath with a relatively high concentration, short stain time approach produces high quality imagery suitable for creating accurate 3D renderings. Micro-CT scanning of heart valves in fluid is shown to be feasible using iodine staining techniques.

Structural Valve Deterioration Is Linked to Increased Immune Infiltrate and Chemokine Expression.

We aim to investigate whether structural valve deterioration (SVD) of bioprosthetic xenogenic tissue heart valves (XTHVs) is associated with increased immune cell infiltration and whether co-expression of several chemokines correlates with this increase in immune infiltrate. Explanted XTHVs from patients undergoing redo valve replacement for SVD were obtained. Immunohistochemical, microscopic, and gene expression analysis approaches were used. XTHVs (n = 37) were obtained from 32 patients (mean 67.7years) after a mean time of 11.6years post-implantation. Significantly increased immune cellular infiltration was observed in the explanted SVD valves for all immune cell types examined, including T cells, macrophages, B cells, neutrophils, and plasma cells, compared to non-SVD controls. Furthermore, a significantly increased chemokine gradient in explanted SVD valves accompanied immune cell infiltration. These data suggest the development of SVD is associated with a significantly increased burden of immune cellular infiltrate correlated to the induction of a chemokine gradient around the XHTV, representing chronic immune rejection.Graphical abstract Proposed interaction between innate and adaptive immunity leading to the development of structural valve deterioration in xenogenic tissue heart valves.

Spectroscopic assessment of oxidative damage in biomolecules and tissues.

Oxidative damage is one of the main causes of cryopreservation injury compromising the use of cryopreserved biospecimens. The aim of this study was to evaluate the use of Fourier transform infrared spectroscopy (FTIR) as a non-invasive method to assess changes in biomolecular composition and structure, associated with oxidative stress in isolated biomolecules, acellular heart valve tissues, and ovarian cortex tissues. FTIR spectra of these specimens subjected to various treatments (H2O2- and Fenton-treatment or elevated temperatures) were vector normalized and selected spectral regions were analyzed by principal component analysis (PCA). Control and damaged biomolecules can easily be separated using PCA score plots. Acellular heart valve tissues that were subjected to different levels of oxidative damage formed separate cluster in PCA score plots. In hydrated ovarian tissue, large variation of the principal components was observed. Drying the ovarian tissues samples resulted in improved cluster separation of treatment groups. However, early signs of oxidative damage under mild stress conditions could not be detected by PCA of FTIR spectra. For the ovarian tissue samples, the standardly used nitro blue tetrazolium chloride (NBT) assay was used to monitor the amount of formazan production, reflecting reactive oxygen species (ROS) production at various temperatures. At 37°C, formazan staining rapidly increased during the first 30min, and then slowly reached a saturation level, but also at lower temperatures (i.e. 4°C) formazan production was observed. In summary, we conclude that ATR-FTIR combined with PCA can be used to study oxidative damage in biomolecules as well as in tissues. In tissues, however, sample heterogeneity makes it difficult to detect early signs of oxidative damage.

Heart valves from polymeric fibers: potential and limits.

Transcatheter aortic valve implantation (TAVI) has become today a popular alternative technique to surgical valve replacement for critical patients. However, with only six years follow-up on average, little is known about the long-term durability of transcatheter implanted biological tissue. Moreover, the high cost of biological tissue harvesting and chemical treatment procedures favor the development of alternative synthetic valve leaflet materials. In that context, thin, flexible and porous textile constructions could be considered as interesting candidates. However, these constructions must be strong enough to withstand the load applied on the leaflet especially in aortic position. Moreover, the interaction of textile material with living tissue should be comparable to biological valve tissue, and the foreign body reaction (FBR) as well as the calcification mechanisms should be controlled. In the frame of heart valve tissue engineering strategies, the use of bioresorbable polymer scaffolds is expected to limit that FBR. However, to precisely control the degradation of the polymer is not trivial. Conversely, when permanent textile polymers are considered, the porosity of the fibrous scaffold tends to induce exaggerated tissue ingrowth which may prevent the implants from remaining flexible. In that context, the ideal synthetic fibrous valve leaflet remains to be found. The purpose of this study was to investigate the possible strategies which have been adopted over the last 50 years regarding the use of textile as heart valve leaflet material. Results showed that textile presented potential, despite remaining strong challenges. It came out that hybrid textiles combining bioresorbable and permanent polymer fibers arranged in both non-woven and woven or knitted way could probably help providing strength and generating appropriate tissue ingrowth.

Anisotropic Fiber-Reinforced Glycosaminoglycan Hydrogels for Heart Valve Tissue Engineering.

This study investigates polymer fiber-reinforced protein-polysaccharide-based hydrogels for heart valve tissue engineering applications. Polycaprolactone and gelatin (3:1) blends were jet-spun to fabricate aligned fibers that possessed fiber diameters in the range found in the native heart valve. These fibers were embedded in methacrylated hydrogels made from gelatin, sodium hyaluronate, and chondroitin sulfate to create fiber-reinforced hydrogel composites (HCs). The fiber-reinforced gelatin glycosaminoglycan (GAG)-based HC possessed interconnected porous structures and porosity higher than fiber-only conditions. These fiber-reinforced HCs exhibited compressive modulus and biaxial mechanical behavior comparable to that of native porcine aortic valves. The fiber-reinforced HCs were able to swell higher and degraded less than the hydrogels. Elution studies revealed that less than 20% of incorporated gelatin methacrylate and GAGs were released over 2 weeks, with a steady-state release after the first day. When cultured with porcine valve interstitial cells (VICs), the fiber-reinforced composites were able to maintain higher cell viability compared with fiber-only samples. Quiescent VICs expressed alpha smooth muscle actin and calponin showing an activated phenotype, along with a few cells expressing the proliferation marker Ki67 and negative expression for RUNX2, an osteogenic marker. Our study demonstrated that compared with the hydrogels and fibers alone, combining both components can yield durable, reinforced composites that mimic heart valve mechanical behavior, while maintaining high cell viability and expressing positive activation as well as proliferation markers.

Dot blots of solubilized extracellular matrix allow quantification of human antibodies bound to epitopes present in decellularized porcine pulmonary heart valves.

The present study reports the development of a sensitive dot blot protocol for determining the level of preformed antibodies against porcine heart valve tissue derived from wild-type (WT) and α-Gal-KO (GGTA1-KO) pigs in human sera. The assay uses decellularized and solubilized heart valve tissue; antibody binding found in this dot blot assay could be correlated with antibody titers of preformed anti-α-Gal and anti-Neu5Gc antibodies detected by a sensitive ELISA. The ultimate protocol had an inter-assay variance of 9.5% and an intra-assay variance of 9.2%, showing that the test is reliable and highly reproducible. With the aid of this dot blot assay, we found significant variation with regard to antibody contents among twelve human sera. Binding of preformed antibodies to WT tissue was significantly higher than to GGTA1-KO tissue. The dot blot assay described herein could be a valuable tool to measure preformed antibody levels in human sera against unknown epitopes on decellularized tissue prior to implantation. Ultimately, this prescreening may allow a matching of the porcine xenograft with the respective human recipients in demand and thus may become an important tool for graft long-term survival similar to current allotransplantation settings.

Next-generation tissue-engineered heart valves with repair, remodelling and regeneration capacity.

Valvular heart disease is a major cause of morbidity and mortality worldwide. Surgical valve repair or replacement has been the standard of care for patients with valvular heart disease for many decades, but transcatheter heart valve therapy has revolutionized the field in the past 15 years. However, despite the tremendous technical evolution of transcatheter heart valves, to date, the clinically available heart valve prostheses for surgical and transcatheter replacement have considerable limitations. The design of next-generation tissue-engineered heart valves (TEHVs) with repair, remodelling and regenerative capacity can address these limitations, and TEHVs could become a promising therapeutic alternative for patients with valvular disease. In this Review, we present a comprehensive overview of current clinically adopted heart valve replacement options, with a focus on transcatheter prostheses. We discuss the various concepts of heart valve tissue engineering underlying the design of next-generation TEHVs, focusing on off-the-shelf technologies. We also summarize the latest preclinical and clinical evidence for the use of these TEHVs and describe the current scientific, regulatory and clinical challenges associated with the safe and broad clinical translation of this technology.

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering.

The concept of tissue engineering evolved long before the phrase was forged, driven by the thromboembolic complications associated with the early total artificial heart programs of the 1960s. Yet more than half a century of dedicated research has not fulfilled the promise of successful broad clinical implementation. A historical account outlines reasons for this scientific impasse. For one, there was a disconnect between distinct eras each characterized by different clinical needs and different advocates. Initiated by the pioneers of cardiac surgery attempting to create neointimas on total artificial hearts, tissue engineering became fashionable when vascular surgeons pursued the endothelialisation of vascular grafts in the late 1970s. A decade later, it were cardiac surgeons again who strived to improve the longevity of tissue heart valves, and lastly, cardiologists entered the fray pursuing myocardial regeneration. Each of these disciplines and eras started with immense enthusiasm but were only remotely aware of the preceding efforts. Over the decades, the growing complexity of cellular and molecular biology as well as polymer sciences have led to surgeons gradually being replaced by scientists as the champions of tissue engineering. Together with a widening chasm between clinical purpose, human pathobiology and laboratory-based solutions, clinical implementation increasingly faded away as the singular endpoint of all strategies. Moreover, a loss of insight into the healing of cardiovascular prostheses in humans resulted in the acceptance of misleading animal models compromising the translation from laboratory to clinical reality. This was most evident in vascular graft healing, where the two main impediments to the in-situ generation of functional tissue in humans remained unheeded–the trans-anastomotic outgrowth stoppage of endothelium and the build-up of an impenetrable surface thrombus. To overcome this dead-lock, research focus needs to shift from a biologically possible tissue regeneration response to one that is feasible at the intended site and in the intended host environment of patients. Equipped with an impressive toolbox of modern biomaterials and deep insight into cues for facilitated healing, reconnecting to the “user needs” of patients would bring one of the most exciting concepts of cardiovascular medicine closer to clinical reality.

Vitrification of Heart Valve Tissues.

Application of the original vitrification protocol used for pieces of heart valves to intact heart valves has evolved over time. Ice-free cryopreservation by Protocol 1 using VS55 is limited to small samples (1-3mL total volume) where relatively rapid cooling and warming rates are possible. VS55 cryopreservation typically provides extracellular matrix preservation with approximately 80% cell viability and tissue function compared with fresh untreated tissues. In contrast, ice-free cryopreservation using VS83, Protocols 2 and 3, permits preservation of large samples (80-100mL total volume) with several advantages over conventional cryopreservation methods and VS55 preservation, including long-term preservation capability at -80°C; better matrix preservation than freezing with retention of material properties; very low cell viability, reducing the risks of an immune reaction in vivo; reduced risks of microbial contamination associated with use of liquid nitrogen; improved in vivo functions; no significant recipient allogeneic immune response; simplified manufacturing process; increased operator safety because liquid nitrogen is not used; and reduced manufacturing costs. More recently, we have developed Protocol 4 in which VS55 is supplemented with sugars resulting in reduced concerns regarding nucleation during cooling and warming. This method can be used for large samples resulting in retention of cell viability and permits short-term exposure to -80°C with long-term storage preferred at or below -135°C.

A Novel Approach for Detecting Unique Variations among Infectious Bacterial Species in Endocarditic Cardiac Valve Vegetation.

Infectious endocarditis (IE) remains one of the deadliest heart diseases with a high death rate, generally following thrombo-embolic events. Today, therapy is based on surgery and antibiotic therapy. When thromboembolic complications in IE patients persist, this is often due to our lack of knowledge regarding the pathophysiological development and organization of cells in the vegetation, most notably the primordial role of platelets and further triggered hemostasis, which is related to the diversity of infectious microorganisms involved. Our objective was to study the organization of IE vegetations due to different bacteria species in order to understand the related pathophysiological mechanism of vegetation development. We present an approach for ultrastructural analysis of whole-infected heart valve tissue based on scanning electron microscopy and energy-dispersive X-ray spectroscopy. Our approach allowed us to detect differences in cell organization between the analyzed vegetations and revealed a distinct chemical feature in viridans Streptococci ones. Our results illustrate the benefits that such an approach may bring for guiding therapy, considering the germ involved for each IE patient.

Comparing Scaffold Design and Recellularization Techniques for Development of Tissue Engineered Heart Valves

Valvular heart disease continues to afflict millions of people around the world. In many cases, the only corrective treatment for valvular heart disease is valve replacement. Valve replacement options are currently limited, and the most common constructs utilized are xenogenic tissue heart valves. The main limitation with the use of this valve type is the development of valve deterioration. Emerging evidence suggests that the underlying driver of valve deterioration is a chronic immune-mediated rejection process of the foreign xenogenic-derived tissue. There is an ongoing focus on the development of an immunologically acceptable, unfixed xenogeneic scaffold for future heart valve constructs. Tissue engineering heart valves are a promising method of developing a durable, non-immunogenic, non-thrombotic, easily implantable, and readily available implant. In this review, we summarize the various decellularization protocols and scaffold designs for tissue engineered heart valve use and highlight the different cell types and methods for recellularization of tissue engineered heart valves. Valve replacement surgery is one of the most common procedures performed by cardiac surgeons. Most patients undergoing valve replacement surgery receive a tissue valve. Tissue valves are made from either cow or pig tissue, and unfortunately tend to fail over time requiring reoperation. One reason these valves fail may be due to a slow rejection of the animal tissue by the human immune system. There is an ongoing focus on the development of artificial heart valves using various tissue engineered designs. The purpose of this review is to summarize various designs and techniques for the creation of artificial heart valves.

Aerococcus urinae - A potent biofilm builder in endocarditis.

The diagnosis of infective endocarditis (IE) remains a challenge. One of the rare bacterial species recently associated with biofilms and negative cultures in infective endocarditis is Aerococcus urinae. Whether the low number of reported cases might be due to lack of awareness and misidentification, mainly as streptococci, is currently being discussed. To verify the relevance and biofilm potential of Aerococcus in endocarditis, we used fluorescence in situ hybridization to visualize the microorganisms within the heart valve tissue. We designed and optimized a specific FISH probe (AURI) for in situ visualization and identification of A. urinae in sections of heart valves from two IE patients whose 16S rRNA gene sequencing had deteced A. urinae. Both patients had a history of urinary tract infections. FISH visualized impressive in vivo grown biofilms in IE, thus confirming the potential of A. urinae as a biofilm pathogen. In both cases, FISH/PCR was the only method to unequivocally identify A. urinae as the only causative pathogen for IE. The specific FISH assay for A. urinae is now available for further application in research and diagnostics. A. urinae should be considered in endocarditis patients with a history of urinary tract infections. These findings support the biofilm potential of A. urinae as a virulence factor and are meant to raise the awareness of this pathogen.

Comparative assessment of immediate outcomes of aortic valve replacement with CE Perimount, Aspire, Hancock-2, UniLine

Aim.To compare hemodynamics between four different aortic tissue valves implanted in the elder patients. The stented bioprostheses sizes were 21, 23, and 25. All bioprostheses were produced by different manufacturers.Methods.135 patients who underwent aortic valve replacement at the Belgorod Regional Clinical Hospital in the period from January 01, 2007 to June 01, 2018 were included in the retrospective non-randomized clinical study. Implantation of 21 mm tissue heart valves was performed in 50 patients, 23 mm - in 66 patients, and 25 mm - in 29 patients. Stented bioprostheses Carpentier-Edwards PERIMOUNT (Edwards, USA), Aspire (Vascutek, USA), Hancock-2 (Medtroniс, USA), and UniLine (NeoCor, Russia) were used in the study.Results.Valve function was estimated by transthoracic echocardiography at days 10-14 postoperatively. Peak gradient, left ventricular stroke volume, the ratio between stroke volume and maximum gradient (SV/∆р mах), the ratio between SV/∆р mах and BSA were measured in all patients. The stented UniLine tissue heart valve (NeoCor) demonstrated superior hydrodynamic parameters, whereas stented Hancock-2 tissue heart valve had inferior ones.Conclusion.Patients who underwent aortic valve replacement with UniLine (NeoCor) reported low peak gradient, improved stroke volume and better peripheral perfusion in the immediate postoperative period. Obtained data suggest that UniLine is more durable and results in better systolic and diastolic left ventricle function, leading to left ventricle hypertrophy regression.

Dental Pulp Stem Cells for Tissue Engineered Heart Valve

Myxomatous mitral valve degeneration is the most acquired heart disease in dogs. To reduce the clinical progression of mitral valve degeneration and achieve the hemodynamic outcomes, many medical or surgical treatments have been motivated. The objectives of this study is to investigate the suitability of puppy deciduous teeth stem cells as a cell source for tissue engineered heart valves in dog with degenerative valve disease. Puppy deciduous teeth stem cells (pDSCs) were seeded on the scaffolds which made from polylactic acid (PLA), polycaprolactone (PLC) and silicone. The mechanical properties of the tissue engineered heart valves leaflets were characterized by biaxial tensile tests. Results showed that, deciduous teeth stem cells capable of differentiating into a variety of cell types. However, the ability of puppy deciduous teeth stem cells to differentiate declined with increasing passage number which correspond to the number of protein surface marker detection have been shown to decrease substantially by the fifth passage. PLA scaffold is significantly higher tensile strength than other materials. However, silicone showed the highest flaccidity. The results from this study may provide high regenerative capability and the essential information for future directions of heart valve tissue engineering.

Unraveling the Mechanisms of Endogenous Tissue Restoration after Bioresorbable Pulmonary Valve Implantation in Sheep

Objective: Endogenous Tissue Restoration (ETR) utilizes the regenerative response of the human body to transform an off-the-shelf available, synthetic, absorbable graft into a living functional valve. Recent preclinical studies have shown the principle of ETR for heart valve grafts to be promising1Bennink G Torri S Brugmans M et al.A novel restorative pulmonary valved conduit in a chronic sheep model: Mid-term hemodynamic function and histologic assessment.J Thorac Cardiovasc Surg. 2018; 155 (doi:10.1016/j.jtcvs.2017.12.046.): 2591-2601Google Scholar,2Kluin J Talacua H Smits AIPM et al.In situ heart valve tissue engineering using a bioresorbable elastomeric implant – From material design to 12 months follow-up in sheep.Biomater. 2017; 125 (doi:10.1016/j.biomaterials.2017.02.007.): 101-117Google Scholar. However, further detailed knowledge on the underlying mechanisms of the material-driven regenerative response remains elusive. The goal of the present study was to gain a mechanistic understanding of these processes by histopathological analysis of ETR heart valves. Methods: In this study, Xeltis Pulmonary Valved Conduits (XPV, Xeltis B.V., Eindhoven, The Netherlands) implanted in an ovine model were analyzed. Explanted valves (follow-up time: 2, 6, 12 (N=5 per timepoint) and 24 months (N=2)) were embedded in paraffin and sectioned longitudinally. Spatiotemporal analysis was performed using a comprehensive sheep-specific antibody panel3Dekker S van Geeman D van den Bogaerdt AJ et al.Sheep-specific immunohistochemical panel for the evaluation of regenerative and inflammatory processes in tissue-engineered heart valves.Front. Cardiovasc. Med. 2018; 5 (doi:10.3389/fcvm.2018.00105.): 105Google Scholar. Results: Detailed knowledge on graft absorption as well as neo-tissue formation and a better understanding of cellular influences was obtained. Interestingly, foreign body giant cells were located within the graft material at iNOS-rich degradation and tissue remodeling sites in the hinge region of the leaflet, starting as early as 2 months after implantation. In the conduit material, on the other hand, foreign body giant cells remained on the outer layers with only limited infiltration into the scaffold material. Interestingly, at the same time point vascularization was observed throughout the conduit material. Extracellular matrix components, such as collagens and elastin were formed in a highly heterogeneous fashion, suggesting an important role for hemodynamic loads on the inflammatory and regenerative processes. Conclusions: Our results enhance the mechanistic understanding of material-driven endogenous tissue restoration. These findings also highlight, the importance of the micro-environment imposed by the graft material on the regenerative response towards a biomaterial. KEYWORD: ICTEHV-O-02 The authors do not declare any conflict of interest.

CD4+ T cells and TGFβ1/MAPK signal pathway involved in the valvular hyperblastosis and fibrosis in patients with rheumatic heart disease

The aim of this study was to investigate the roles of CD4+ T cells and transforming growth factor beta (TGFβ1) in the pathological process of valvular hyperblastosis and fibrosis of patients with rheumatic heart disease (RHD). A total of 151 patients were enrolled, among whom, 78 patients were with RHD, and 73 were age and gender matched RHD negative patients. Blood samples and valve specimens were collected for analysis. Pathological changes and collagen fibers contents of valves were analyzed using HE and Masson staining. Percentage of peripheral blood CD4+ T cells was tested through flow cytometry. TGFβ1 level in serum were identified by ELISA. CD4+ T cells infiltration and expression of TGFβ1, p-p38, p-JNK, p-ERK in valves were detected by immunohistochemistry. The mRNA and protein levels of p38, JNK, ERK, TGFβ1, I-collagen and α-SMA were detected by qRT-PCR and western blotting, respectively. The heart valve tissues of RHD patients showed higher degrees of fibrosis, calcification and lymphocytes infiltration, which were mainly CD4+ T cells. In addition, compared with control group, RHD patients had more total CD4+ T cells in peripheral blood and valve tissues. Expression of TGFβ1, phosphorylation of JNK and p38, and synthesis of I-collagen in valve tissues of RHD patients were also significantly increased. Furthermore, we found a strong positive correlation between TGFβ1 expression and phosphorylation of JNK and p38. CD4+ T cells, and fibrogenic cytokine TGFβ1, which activate the intracellular MAPK signaling pathway may participate in the fibrosis of heart valve in RHD patients.

Polymer Fiber-reinforced GAG Based Hydrogel Scaffolds for Heart Valve Tissue Engineering

Objective: An ideal scaffold for TE valve replacement requires native features such as the anisotropic collagen architecture and its surrounding GAG matrix. In this study, we propose to fabricate a...

The First Implantation of the Novel Biological Heart Valve, the Inspiris Resilia Aortic Tissue Valve in Africa

The durability of artificial bioprosthestic or tissue heart valves is limited by structural valve deterioration (SVD) due to long-term calcification especially in young patients and in Africa. A novel bioprosthestic valve, the Resilia Inspiris Aortic Tissue Valve has been developed which, in preclinical studies, has shown reduced calcification thus improving durability. The <i>Inspiris Resilia Aortic Valve</i> is a stented tri-leaflet valve made from bovine pericardial tissue. The tissue is created by treating bovine pericardial tissue with Edwards Integrity Preservation. It incorporates a stable capping anticalcification process, which blocks residual aldehyde groups known to bind with calcium. Tissue preservation with glycerol allows the valve to be stored without a traditional liquid-based solution, such as glutaraldehyde. Therefore, the valve is stored under dry packaging conditions and consequently does not require rinsing prior to implantation. The novel tissue preservation technology significantly improves hemodynamic and anticalcification properties compared with the standard artificial bioprosthestic aortic valve, the Perimount tissue valve. The experience of the implantation of this valve in Africa is limited for there seems to be no published experience of the behaviour of the implantation of this special long lasting bioprosthestic valve in Africa and therefore the purpose of this paper is to share our initial experience of the first successful implantation of this <i>Inspiris Resilia Aortic Valve^™</i> in Ghana, Africa. The implantation was done in a 57-year-old patient who presented with symptomatic moderate to severe aortic valve regurgitation with adequate left ventricular systolic function. He has been followed-up for a year now with well-healed wounds and a transthoracic echocardiography revealing a well-seated valve with no regurgitant flow or paravalvular leak. This is the first report describing the use of the new Inspiris Resilia Aortic valve which has increased durability and does not require anticoagulation in Africa as far as we know.

Structure and Rheological Properties of Bovine Aortic Heart Valve and Pericardium Tissue: Implications in Bioprosthetic and Tissue-Engineered Heart Valves.

Heart valve (HV) diseases are among the leading causes of cardiac failure and deaths. Of the various HV diseases, damaged HV leaflets are among the primary culprits. In many cases, impaired HV restoration is not always possible, and the replacement of valves becomes necessary. Bioprosthetic HVs have been used for the replacement of the diseased valves, which is obtained from the sources of bovine and porcine origin, while tissue-engineered heart valves (TEHV) have emerged as a promising future solution. The bioprosthetic valves are prone to become calcified, and thus they last for only ten to fifteen years. The adequate understanding of the correlations between the biomechanics and rheological properties of native HV tissues can enable us to improve the durability of the bioprosthetic HV as well as help in the development of tissue-engineered heart valves (TEHV). In this study, the structural and rheological properties of native bovine aortic HV and pericardium tissues were investigated. The microstructures of the tissues were investigated using scanning electron microscopy, while the rheological properties were studied using oscillatory shear measurement and creep test. The reported results provide significant insights into the correlations between the microstructure and viscoelastic properties of the bovine aortic HV and pericardium tissues.

TGF-β Signaling Promotes Tissue Formation during Cardiac Valve Regeneration in Adult Zebrafish

Cardiac valve disease can lead to severe cardiac dysfunction and is thus a frequent cause of morbidity and mortality. Its main treatment is valve replacement, which is currently greatly limited by the poor recellularization and tissue formation potential of the implanted valves. As we still lack suitable animal models to identify modulators of these processes, here we used adult zebrafish and found that, upon valve decellularization, they initiate a rapid regenerative program that leads to the formation of new functional valves. After injury, endothelial and kidney marrow-derived cells undergo cell cycle re-entry and differentiate into new extracellular matrix-secreting valve cells. The TGF-β signaling pathway promotes the regenerative process by enhancing progenitor cell proliferation as well as valve cell differentiation. These findings reveal a key role for TGF-β signaling in cardiac valve regeneration and establish the zebrafish as a model to identify and test factors promoting cardiac valve recellularization and growth.