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engineered heart tissue

Mehrdad Namdari, Ali Eatemadi
Heart valves are currently under thorough investigation in tissue engineering (TE) research. Mechanical and biological heart valve prostheses which are recently used have several shortcomings. While allogenic and xenogenic biological prostheses are related to graft rejection, degeneration and thrombosis, resulting in a high rate of reoperation. Mechanical prostheses on the other hand are based on metallic, carbon, and polymeric components, and require continuous treatment with anticoagulant, which result in adverse reactions, e...
October 22, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Inge A E W van Loosdregt, Sylvia Dekker, Patrick W Alford, Cees W J Oomens, Sandra Loerakker, Carlijn V C Bouten
Understanding cell contractility is of fundamental importance for cardiovascular tissue engineering, due to its major impact on the tissue's mechanical properties as well as the development of permanent dimensional changes, e.g., by contraction or dilatation of the tissue. Previous attempts to quantify contractile cellular stresses mostly used strongly aligned monolayers of cells, which might not represent the actual organization in engineered cardiovascular tissues such as heart valves. In the present study, therefore, we investigated whether differences in organization affect the magnitude of intrinsic stress generated by individual myofibroblasts, a frequently used cell source for in vitro engineered heart valves...
October 24, 2016: Cardiovascular Engineering and Technology
Ibrahim J Domian, Hanry Yu, Nikhil Mittal
In this essay the authors argue that chamber pressure dominates the biomechanics of the contraction cycle of the heart, while tissue stiffness dominates the relaxation cycle. This appears to be an under-recognized challenge in cardiac tissue engineering. Optimal approaches will involve constructing chambers or modulating the stiffness of the scaffold/substrate in synchrony with the beating cycle.
October 24, 2016: Advanced Healthcare Materials
Z Riedelová-Reicheltová, E Brynda, T Riedel
Fibrin is a versatile biopolymer that has been extensively used in tissue engineering. In this paper fibrin nanostructures prepared using a technique based on the catalytic effect of fibrin-bound thrombin are presented. This technique enables surface-attached thin fibrin networks to form with precisely regulated morphology without the development of fibrin gel in bulk solution. Moreover, the influence of changing the polymerization time, along with the antithrombin III and heparin concentrations on the morphology of fibrin nanostructures was explored...
October 20, 2016: Physiological Research
Hung X Nguyen, Robert D Kirkton, Nenad Bursac
The ability to directly enhance electrical excitability of human cells is hampered by the lack of methods to efficiently overexpress large mammalian voltage-gated sodium channels (VGSC). Here we describe the use of small prokaryotic sodium channels (BacNav) to create de novo excitable human tissues and augment impaired action potential conduction in vitro. Lentiviral co-expression of specific BacNav orthologues, an inward-rectifying potassium channel, and connexin-43 in primary human fibroblasts from the heart, skin or brain yields actively conducting cells with customizable electrophysiological phenotypes...
October 18, 2016: Nature Communications
Maurizio Pesce, Elisa Messina, Isotta Chimenti, Antonio Paolo Beltrami
The life-long story of the heart starts concomitantly with primary differentiation events occurring in multipotent progenitors located in the so called heart tube. This initially tubular structure starts a looping process which leads to formation of the final four chambered heart with a primary contribution of geometric and position-associated cell sensing. While this establishes the correct patterning of the final cardiac structure, it also feedbacks to fundamental cellular machineries controlling proliferation and differentiation, thus ensuring a coordinated restriction of cell growth and a myocyte terminal differentiation...
October 13, 2016: Stem Cells and Development
Ashkan Shafiee, Anthony Atala
The goal of tissue engineering is to mitigate the critical shortage of donor organs via in vitro fabrication of functional biological structures. Tissue engineering is one of the most prominent examples of interdisciplinary fields, where scientists with different backgrounds work together to boost the quality of life by addressing critical health issues. Many different fields, such as developmental and molecular biology, as well as technologies, such as micro- and nanotechnologies and additive manufacturing, have been integral for advancing the field of tissue engineering...
September 30, 2016: Annual Review of Medicine
Petra E Dijkman, Emanuela S Fioretta, Laura Frese, Francesco S Pasqualini, Simon P Hoerstrup
The incidence of severe valvular dysfunctions (e.g., stenosis and insufficiency) is increasing, leading to over 300,000 valves implanted worldwide yearly. Clinically used heart valve replacements lack the capacity to grow, inherently requiring repetitive and high-risk surgical interventions during childhood. The aim of this review is to present how different tissue engineering strategies can overcome these limitations, providing innovative valve replacements that proved to be able to integrate and remodel in pre-clinical experiments and to have promising results in clinical studies...
July 2016: Transfusion Medicine and Hemotherapy
Yu Shrike Zhang, Andrea Arneri, Simone Bersini, Su-Ryon Shin, Kai Zhu, Zahra Goli-Malekabadi, Julio Aleman, Cristina Colosi, Fabio Busignani, Valeria Dell'Erba, Colin Bishop, Thomas Shupe, Danilo Demarchi, Matteo Moretti, Marco Rasponi, Mehmet Remzi Dokmeci, Anthony Atala, Ali Khademhosseini
Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium...
December 2016: Biomaterials
Napachanok Mongkoldhumrongkul, Najma Latif, Magdi H Yacoub, Adrian H Chester
Responses of valve endothelial cells (VECs) to shear stresses are important for the regulation of valve durability. However, the effect of flow patterns subjected to VECs on the opposite surfaces of the valves on the production of extracellular matrix (ECM) has not yet been investigated. This study aims to investigate the response of side-specific flow patterns, in terms of ECM synthesis and/or degradation in porcine aortic valves. Aortic and ventricular sides of aortic valve leaflets were exposed to oscillatory and laminar flow generated by a Cone-and-Plate machine for 48 h...
October 5, 2016: Cardiovascular Engineering and Technology
Emanuela S Fioretta, Petra E Dijkman, Maximilian Y Emmert, Simon P Hoerstrup
Heart valve replacement is often the only solution for patients suffering from valvular heart disease. However, currently available valve replacements require either life-long anti-coagulation or are associated with valve degeneration and calcification. Moreover, they are suboptimal for young patients, because they do not adapt to the somatic growth. Tissue-engineering has been proposed as a promising approach to fulfill the urgent need for heart valve replacements with regenerative and growth capacity. This review will start with an overview on the currently available valve substitutes and the techniques for heart valve replacement...
September 30, 2016: Journal of Tissue Engineering and Regenerative Medicine
Gordana Vunjak-Novakovic
Tissue-engineered regeneration of a failing human heart remains a major challenge, while cardiovascular disease continues to take more lives than all cancers combined. Much has been learned from the basic and clinical studies, with the most interesting developments happening at the interfaces of disciplines. This seems to be the right time to step back and rethink the evolving paradigm of tissue engineering, and to reflect about the most promising directions to take. We clearly need new therapeutic modalities that are effective and yet simple enough to be practical, and the field is looking into the therapeutic potential of stem-progenitor cells, cardiac and vascular, that are enabled by bioactive factors and functionalized biomaterials...
September 6, 2016: Journal of Thoracic and Cardiovascular Surgery
Andrew J Percy, Sarah A Michaud, Armando Jardim, Nicholas J Sinclair, Suping Zhang, Yassene Mohammed, Andrea L Palmer, Darryl B Hardie, Juncong Yang, Andre M LeBlanc, Christoph H Borchers
The mouse is the most commonly used laboratory animal, with more than 14 million mice being used for research each year in North America alone. The number and diversity of mouse models is increasing rapidly through genetic engineering strategies, but detailed characterization of these models is still challenging because most phenotypic information is derived from time-consuming histological and biochemical analyses. To expand the biochemists' toolkit, we generated a set of targeted proteomic assays for mouse plasma and heart tissue, utilizing bottom-up LC/MRM-MS with isotope-labeled peptides as internal standards...
September 30, 2016: Proteomics
Aida Llucià-Valldeperas, Carolina Soler-Botija, Carolina Gálvez-Montón, Santiago Roura, Cristina Prat-Vidal, Isaac Perea-Gil, Benjamin Sanchez, Ramon Bragos, Gordana Vunjak-Novakovic, Antoni Bayes-Genis
: : Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue-engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time...
September 29, 2016: Stem Cells Translational Medicine
Heather N Hutson, Taylor Marohl, Matthew Anderson, Kevin Eliceiri, Paul Campagnola, Kristyn S Masters
Disorganization of the valve extracellular matrix (ECM) is a hallmark of calcific aortic valve disease (CAVD). However, while microarchitectural features of the ECM can strongly influence the biological and mechanical behavior of tissues, little is known about the ECM microarchitecture in CAVD. In this work, we apply advanced imaging techniques to quantify spatially heterogeneous changes in collagen microarchitecture in CAVD. Human aortic valves were obtained from individuals between 50 and 75 years old with no evidence of valvular disease (healthy) and individuals who underwent valve replacement surgery due to severe stenosis (diseased)...
2016: PloS One
Tze-Wen Chung, Hsin-Yu Lo, Tzung-Han Chou, Jan-Hou Chen, Shoei-Shen Wang
Bone marrow-derived mesenchymal stem cell microtissues (BMSCMT) enhanced cardiomyogenesis in vitro and cardiac repairs of myocardial infarcted hearts in vivo are documented. Producing human BMSCMT onto patches in vitro for cardiac tissue engineering has not been reported. For possibly producing human bone marrow-derived mesenchymal stem cell microtissues (hBMSCMT) on an elastic silk fibroin (SF)-poly(ε-caprolactone) (PCL) based patches is hereby designed. After an elastic SF-PCL (SP) patch is fabricated, hyaluronic acid (HA)/SF-PCL(HSP) and HA-GRGD/SF-PCL(HGSP) patches are fabricated by photochemically grafting HA and HA-GRGD onto SP surfaces...
September 28, 2016: Macromolecular Bioscience
Zeeshan Syedain, Jay Reimer, Matthew Lahti, James Berry, Sandra Johnson, Robert T Tranquillo
Treatment of congenital heart defects in children requiring right ventricular outflow tract reconstruction typically involves multiple open-heart surgeries because all existing graft materials have no growth potential. Here we present an 'off-the-shelf' vascular graft grown from donor fibroblasts in a fibrin gel to address this critical unmet need. In a proof-of-concept study, the decellularized grafts are implanted as a pulmonary artery replacement in three young lambs and evaluated to adulthood. Longitudinal ultrasounds document dimensional growth of the grafts...
September 27, 2016: Nature Communications
Luis G Hurtado-Aguilar, Shane Mulderrig, Ricardo Moreira, Nima Hatam, Jan Spillner, Thomas Schmitz-Rode, Stefan Jockenhoevel, Petra Mela
Tissue-engineered heart valves are developed in bioreactors where biochemical and mechanical stimuli are provided for extracellular matrix formation. During this phase, the monitoring possibilities are limited by the need to maintain the sterility and the integrity of the valve. Therefore, noninvasive and nondestructive techniques are required. As such, optical imaging is commonly used to verify valve's functionality in vitro. It provides important information (i.e. leaflet symmetry, geometric orifice area, closing and opening times) which is, however, usually limited to a singular view along the central axis from the outflow side...
September 27, 2016: Tissue Engineering. Part C, Methods
Ahmet U Uzun, Ingra Mannhardt, Kaja Breckwoldt, András Horváth, Silke S Johannsen, Arne Hansen, Thomas Eschenhagen, Torsten Christ
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) provide a unique opportunity to study human heart physiology and pharmacology and repair injured hearts. The suitability of hiPSC-CM critically depends on how closely they share physiological properties of human adult cardiomyocytes (CM). Here we investigated whether a 3D engineered heart tissue (EHT) culture format favors maturation and addressed the L-type Ca(2+)-current (ICa,L) as a readout. The results were compared with hiPSC-CM cultured in conventional monolayer (ML) and to our previous data from human adult atrial and ventricular CM obtained when identical patch-clamp protocols were used...
2016: Frontiers in Pharmacology
Nobuyasu Kato, Masaaki Yamagishi, Keiichi Kanda, Takako Miyazaki, Yoshinobu Maeda, Masashi Yamanami, Taiji Watanabe, Hitoshi Yaku
PURPOSE: The ideal material for pediatric pulmonary artery (PA) augmentation is autologous pericardium. However, its utility for multistaged operations is limited. In this study, we applied an in vivo tissue-engineered autologous Biotube graft to a patient with congenital heart disease for the first time. DESCRIPTION: For molds of the Biotubes, two silicone 19F drain tubes were embedded in the subcutaneous spaces of a 2-year-old girl with a diagnosis of pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries during palliative surgical procedures...
October 2016: Annals of Thoracic Surgery
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