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      Fabrication and In Vitro Characterization of a Tissue Engineered PCL-PLLA Heart Valve

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          Abstract

          Heart valve diseases are among the leading causes of cardiac failure around the globe. Nearly 90,000 heart valve replacements occur in the USA annually. Currently, available options for heart valve replacement include bioprosthetic and mechanical valves, both of which have severe limitations. Bioprosthetic valves can last for only 10–20 years while patients with mechanical valves always require blood-thinning medications throughout the remainder of the patient’s life. Tissue engineering has emerged as a promising solution for the development of a viable, biocompatible and durable heart valve; however, a human implantable tissue engineered heart valve is yet to be achieved. In this study, a tri-leaflet heart valve structure is developed using electrospun polycaprolactone (PCL) and poly L-lactic acid (PLLA) scaffolds, and a set of in vitro testing protocol has been developed for routine manufacturing of tissue engineered heart valves. Stress-strain curves were obtained for mechanical characterization of different valves. The performances of the developed valves were hemodynamically tested using a pulse duplicator, and an echocardiography machine. Results confirmed the superiority of the PCL-PLLA heart valve compared to pure PCL or pure PLLA. The developed in vitro test protocol involving pulse duplicator and echocardiography tests have enormous potential for routine application in tissue engineering of heart valves.

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          Biomedical applications of polymer-composite materials: a review

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            Microfluidic techniques for development of 3D vascularized tissue.

            Development of a vascularized tissue is one of the key challenges for the successful clinical application of tissue engineered constructs. Despite the significant efforts over the last few decades, establishing a gold standard to develop three dimensional (3D) vascularized tissues has still remained far from reality. Recent advances in the application of microfluidic platforms to the field of tissue engineering have greatly accelerated the progress toward the development of viable vascularized tissue constructs. Numerous techniques have emerged to induce the formation of vascular structure within tissues which can be broadly classified into two distinct categories, namely (1) prevascularization-based techniques and (2) vasculogenesis and angiogenesis-based techniques. This review presents an overview of the recent advancements in the vascularization techniques using both approaches for generating 3D vascular structure on microfluidic platforms.
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              Biomechanical properties of native and tissue engineered heart valve constructs.

              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. Therefore, the success of future heart valve tissue engineering approaches depends on the ability of the TEHV to mimic and maintain the functional and mechanical properties of the native heart valves. However, aside from some tensile quasistatic data and flexural or bending properties, detailed mechanical properties such as dynamic fatigue, creep behavior, and viscoelastic properties of heart valves are still poorly understood. The need for better understanding and more detailed characterization of mechanical properties of tissue engineered, as well as native heart valve constructs is thus evident. In the current review we aim to present an overview of the current understanding of the mechanical properties of human and common animal model heart valves. The relevant data on both native and tissue engineered heart valve constructs have been compiled and analyzed to help in defining the target ranges for mechanical properties of TEHV constructs, particularly for the aortic and the pulmonary valves. We conclude with a summary of perspectives on the future work on better understanding of the mechanical properties of TEHV constructs.
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                Author and article information

                Contributors
                ahasan@qu.edu.qa
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                29 May 2018
                29 May 2018
                2018
                : 8
                : 8187
                Affiliations
                [1 ]ISNI 0000 0004 0634 1084, GRID grid.412603.2, Department of Mechanical and Industrial Engineering, , College of Engineering, Qatar University, ; Doha, Qatar
                [2 ]Biostage, Inc., Holliston, MA 01746 USA
                [3 ]ISNI 0000 0004 1936 9801, GRID grid.22903.3a, Biomedical Engineering, Faculty of Engineering and Architecture, , American University of Beirut, ; Beirut, 11-0236 Lebanon
                [4 ]Division of Qatar Cardiovascular Research Center, Sidra Medicine, Doha, Qatar
                [5 ]ISNI 0000 0000 8683 5797, GRID grid.413676.1, Imperial College, , NHLI, Heart Science Centre, Harefield, ; Middlesex, UB9 6JH United Kingdom
                [6 ]ISNI 0000 0004 0634 1084, GRID grid.412603.2, Biomedical Research Center, , Qatar University, ; Doha, PO Box 2713 Qatar
                Author information
                http://orcid.org/0000-0001-8380-2233
                http://orcid.org/0000-0002-3511-7191
                Article
                26452
                10.1038/s41598-018-26452-y
                5974353
                29844329
                67232fea-23a6-4339-aa38-2f075a21d883
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 May 2017
                : 25 April 2018
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