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Anwarul Hasan, John Saliba, Hassan Pezeshgi Modarres, Ahmed Bakhaty, Amir Nasajpour, Mohammad R K Mofrad, Amir Sanati-Nezhad
Due to the increased morbidity and mortality resulting from heart valve diseases, there is a growing demand for off-the-shelf implantable tissue engineered heart valves (TEHVs). Despite the significant progress in recent years in improving the design and performance of TEHV constructs, viable and functional human implantable TEHV constructs have remained elusive. The recent advances in micro and nanoscale technologies including the microfabrication, nano-microfiber based scaffolds preparation, 3D cell encapsulated hydrogels preparation, microfluidic, micro-bioreactors, nano-microscale biosensors as well as the computational methods and models for simulation of biological tissues have increased the potential for realizing viable, functional and implantable TEHV constructs...
October 2016: Biomaterials
Yang Yang, Chongxi Fan, Chao Deng, Lin Zhao, Wei Hu, Shouyin Di, Zhiqiang Ma, Yu Zhang, Zhigang Qin, Zhenxiao Jin, Xiaolong Yan, Shuai Jiang, Yang Sun, Wei Yi
Tissue-engineered heart valves (TEHVs) are a promising treatment for valvular heart disease, although their application is limited by high flow shear stress (FSS). Melatonin has a wide range of physiological functions and is currently under clinical investigation for expanded applications; moreover, extensive protective effects on the cardiovascular system have been reported. In this study, we investigated the protection conferred by melatonin supplementation against FSS-induced injury in bone marrow mesenchymal stem cells (BMSCs) and elucidated the potential mechanism in this process...
March 2016: Journal of Pineal Research
Sandra Loerakker, Tommaso Ristori, Frank P T Baaijens
One of the most critical problems in heart valve tissue engineering is the progressive development of valvular insufficiency due to leaflet retraction. Understanding the underlying mechanisms of this process is crucial for developing tissue-engineered heart valves (TEHVs) that maintain their functionality in the long term. In the present study, we adopted a computational approach to predict the remodeling process in TEHVs subjected to dynamic pulmonary and aortic pressure conditions, and to assess the risk of valvular insufficiency...
May 2016: Journal of the Mechanical Behavior of Biomedical Materials
Sasmita Rath, Manuel Salinas, Ana G Villegas, Sharan Ramaswamy
For treatment of critical heart valve diseases, prosthetic valves perform fairly well in most adults; however, for pediatric patients, there is the added requirement that the replacement valve grows with the child, thus extremely limiting current treatment options. Tissue engineered heart valves (TEHV), such as those derived from autologous bone marrow stem cells (BMSCs), have the potential to recapitulate native valve architecture and accommodate somatic growth. However, a fundamental pre-cursor in promoting directed integration with native tissues rather than random, uncontrolled growth requires an understanding of BMSC mechanobiological responses to valve-relevant mechanical environments...
2015: PloS One
Gabriel L Converse, Eric E Buse, Kari R Neill, Christopher R McFall, Holley N Lewis, Mitchell C VeDepo, Rachael W Quinn, Richard A Hopkins
Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC)...
October 15, 2015: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Maryam Eslami, Gholamreza Javadi, Nasser Agdami, Mohammad Ali Shokrgozar
OBJECTIVE: The incidence of heart valve disease is increasing worldwide and the number of heart valve replacements is expected to increase in the future. By mimicking the main tissue structures and properties of heart valve, tissue engineering offers new options for the replacements. Applying an appropriate scaffold in fabricating tissue-engineered heart valves (TEHVs) is of importance since it affects the secretion of the main extracellular matrix (ECM) components, collagen 1 and elastin, which are crucial in providing the proper mechanical properties of TEHVs...
2015: Cell Journal
Francesco C Origgi, Marco Tecilla, Paola Pilo, Fabio Aloisio, Patricia Otten, Lisandra Aguilar-Bultet, Ursula Sattler, Paola Roccabianca, Carlos H Romero, David C Bloom, Elliott R Jacobson
We report the first de novo sequence assembly and analysis of the genome of Testudinid herpesvirus 3 (TeHV3), one of the most pathogenic chelonian herpesviruses. The genome of TeHV3 is at least 150,080 nucleotides long, is arranged in a type D configuration and comprises at least 102 open reading frames extensively co-linear with those of Human herpesvirus 1. Consistently, the phylogenetic analysis positions TeHV3 among the Alphaherpesvirinae, closely associated with Chelonid herpesvirus 5, a Scutavirus. To date, there has been limited genetic characterization of TeHVs and a resolution beyond the genotype was not feasible because of the lack of informative DNA sequences...
2015: PloS One
Isra Marei, Adrian Chester, Ivan Carubelli, Themistoklis Prodromakis, Tatiana Trantidou, Magdi H Yacoub
BACKGROUND: Scaffolds are a key component of tissue-engineered heart valves (TEHVs). Several approaches had been adopted in the design of scaffolds using both natural and synthetic resources. We have investigated the suitability of parylene C (PC), a vapor deposited polymeric material, for the use as a scaffold in TEHV. AIMS: To evaluate the adsorption of extracellular matrix components onto plasma-activated PC and study the biocompatibility of PC by measuring cellular adhesion, viability, apoptosis, and phenotypic expression of valve endothelial and interstitial cells...
October 2015: Tissue Engineering. Part A
Samaneh Ghazanfari, Anita Driessen-Mol, Bart Sanders, Petra E Dijkman, Simon P Hoerstrup, Frank P T Baaijens, Carlijn V C Bouten
BACKGROUND: Decellularized tissue-engineered heart valves (TEHVs) are under investigation as alternative for current heart valve prostheses with the potential to rapidly repopulate with cells within the body. Ideally, these valves are stented for transapical or minimally invasive delivery. It is unclear if and how the matrix of these valves remodels under in vivo hemodynamic loading conditions and in the presence of a stent. Here, we study the evolution of collagen orientation and tissue maturation in the wall of stented decellularized TEHVs with time after implantation...
August 2015: Tissue Engineering. Part A
Sasmita Rath, Manuel Salinas, Smita Bhatacharjee, Sharan Ramaswamy
Fluid-induced oscillatory shear stress (OSS) and nicotine are known antagonists in cardiovascular disease. However, from a regenerative medicine standpoint, we hypothesized that these parameters may support the cell differentiation of bone marrow mesenchymal stem cells (BMMSCs) for engineering heart valves. In this study, OSS and nicotine (10-6M) were applied individually to BMMSCs in monolayer culture. In both cases, a significantly higher expression of CD31 was detected compared to corresponding controls (p<0...
2015: Journal of Long-term Effects of Medical Implants
Iyore A James, Tai Yi, Shuhei Tara, Cameron A Best, Alexander J Stuber, Kejal V Shah, Blair F Austin, Tadahisa Sugiura, Yong-Ung Lee, Joy Lincoln, Aaron J Trask, Toshiharu Shinoka, Christopher K Breuer
Decellularized allograft heart valves have been used as tissue-engineered heart valve (TEHV) scaffolds with promising results; however, little is known about the cellular mechanisms underlying TEHV neotissue formation. To better understand this phenomenon, we developed a murine model of decellularized pulmonary heart valve transplantation using a hemodynamically unloaded heart transplant model. Furthermore, because the hemodynamics of blood flow through a heart valve may influence morphology and subsequent function, we describe a modified loaded heterotopic heart transplant model that led to an increase in blood flow through the pulmonary valve...
September 2015: Tissue Engineering. Part C, Methods
Miriam Weber, Israel Gonzalez de Torre, Ricardo Moreira, Julia Frese, Caroline Oedekoven, Matilde Alonso, Carlos J Rodriguez Cabello, Stefan Jockenhoevel, Petra Mela
Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold...
August 2015: Tissue Engineering. Part C, Methods
Bin Duan, Laura A Hockaday, Shoshana Das, Charlie Xu, Jonathan T Butcher
Living tissue-engineered heart valves (TEHV) would be a major benefit for children who require a replacement with the capacity for growth and biological integration. A persistent challenge for TEHV is accessible human cell source(s) that can mimic native valve cell phenotypes and matrix remodeling characteristics that are essential for long-term function. Mesenchymal stem cells derived from bone marrow (BMMSC) or adipose tissue (ADMSC) are intriguing cell sources for TEHV, but they have not been compared with pediatric human aortic valve interstitial cells (pHAVIC) in relevant 3D environments...
August 2015: Tissue Engineering. Part C, Methods
Nafiseh Masoumi, Nasim Annabi, Alexander Assmann, Benjamin L Larson, Jesper Hjortnaes, Neslihan Alemdar, Mahshid Kharaziha, Keefe B Manning, John E Mayer, Ali Khademhosseini
Tissue engineered heart valves (TEHVs) that can grow and remodel have the potential to serve as permanent replacements of the current non-viable prosthetic valves particularly for pediatric patients. A major challenge in designing functional TEHVs is to mimic both structural and anisotropic mechanical characteristics of the native valve leaflets. To establish a more biomimetic model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning and microfabrication techniques. These constructs were fabricated by assembling microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone) (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic mechanical properties similar to the mechanical characteristics of the native heart valves...
September 2014: Biomaterials
Nafiseh Masoumi, Benjamin L Larson, Nasim Annabi, Mahshid Kharaziha, Behnam Zamanian, Kayle S Shapero, Alexander T Cubberley, Gulden Camci-Unal, Keefe B Manning, John E Mayer, Ali Khademhosseini
Tissue engineered heart valves (TEHV) can be useful in the repair of congenital or acquired valvular diseases due to their potential for growth and remodeling. The development of biomimetic scaffolds is a major challenge in heart valve tissue engineering. One of the most important structural characteristics of mature heart valve leaflets is their intrinsic anisotropy, which is derived from the microstructure of aligned collagen fibers in the extracellular matrix (ECM). In the present study, a directional electrospinning technique is used to fabricate fibrous poly(glycerol sebacate):poly(caprolactone) (PGS:PCL) scaffolds containing aligned fibers, which resemble native heart valve leaflet ECM networks...
June 2014: Advanced Healthcare Materials
Anita Driessen-Mol, Maximilian Y Emmert, Petra E Dijkman, Laura Frese, Bart Sanders, Benedikt Weber, Nikola Cesarovic, Michele Sidler, Jori Leenders, Rolf Jenni, Jürg Grünenfelder, Volkmar Falk, Frank P T Baaijens, Simon P Hoerstrup
OBJECTIVES: This study sought to evaluate long-term in vivo functionality, host cell repopulation, and remodeling of "off-the-shelf" tissue engineered transcatheter homologous heart valves. BACKGROUND: Transcatheter valve implantation has emerged as a valid alternative to conventional surgery, in particular for elderly high-risk patients. However, currently used bioprosthetic transcatheter valves are prone to progressive dysfunctional degeneration, limiting their use in younger patients...
April 8, 2014: Journal of the American College of Cardiology
Anwarul Hasan, Kim Ragaert, Wojciech Swieszkowski, Seila Selimović, Arghya Paul, Gulden Camci-Unal, Mohammad R K Mofrad, Ali Khademhosseini
Due to the increasing number of heart valve diseases, there is an urgent clinical need for off-the-shelf tissue engineered heart valves. While significant progress has been made toward improving the design and performance of both mechanical and tissue engineered heart valves (TEHVs), a human implantable, functional, and viable TEHV has remained elusive. In animal studies so far, the implanted TEHVs have failed to survive more than a few months after transplantation due to insufficient mechanical properties...
June 27, 2014: Journal of Biomechanics
Inge A E W van Loosdregt, Giulia Argento, Anita Driessen-Mol, Cees W J Oomens, Frank P T Baaijens
Preclinical studies of tissue-engineered heart valves (TEHVs) showed retraction of the heart valve leaflets as major failure of function mechanism. This retraction is caused by both passive and active cell stress and passive matrix stress. Cell-mediated retraction induces leaflet shortening that may be counteracted by the hemodynamic loading of the leaflets during diastole. To get insight into this stress balance, the amount and duration of stress generation in engineered heart valve tissue and the stress imposed by physiological hemodynamic loading are quantified via an experimental and a computational approach, respectively...
June 27, 2014: Journal of Biomechanics
Zeeshan H Syedain, Lee A Meier, Jay M Reimer, Robert T Tranquillo
A novel tissue-engineered heart valve (TEHV) was fabricated from a decellularized tissue tube mounted on a frame with three struts, which upon back-pressure cause the tube to collapse into three coapting "leaflets." The tissue was completely biological, fabricated from ovine fibroblasts dispersed within a fibrin gel, compacted into a circumferentially aligned tube on a mandrel, and matured using a bioreactor system that applied cyclic distension. Following decellularization, the resulting tissue possessed tensile mechanical properties, mechanical anisotropy, and collagen content that were comparable to native pulmonary valve leaflets...
December 2013: Annals of Biomedical Engineering
Miriam Weber, Eriona Heta, Ricardo Moreira, Valentine N Gesche, Thomas Schermer, Julia Frese, Stefan Jockenhoevel, Petra Mela
The general approach in heart valve tissue engineering is to mimic the shape of the native valve in the attempt to recreate the natural haemodynamics. In this article, we report the fabrication of the first tissue-engineered heart valve (TEHV) based on a tubular leaflet design, where the function of the leaflets of semilunar heart valves is performed by a simple tubular construct sutured along a circumferential line at the root and at three single points at the sinotubular junction. The tubular design is a recent development in pericardial (nonviable) bioprostheses, which has attracted interest because of the simplicity of the construction and the reliability of the implantation technique...
April 2014: Tissue Engineering. Part C, Methods
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