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      A Novel Hybrid Membrane VAD as First Step Toward Hemocompatible Blood Propulsion

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          Abstract

          Heart failure is a raising cause of mortality. Heart transplantation and ventricular assist device (VAD) support represent the only available lifelines for end stage disease. In the context of donor organ shortage, the future role of VAD as destination therapy is emerging. Yet, major drawbacks are connected to the long-term implantation of current devices. Poor VAD hemocompatibility exposes the patient to life-threatening events, including haemorrhagic syndromes and thrombosis. Here, we introduce a new concept of artificial support, the Hybrid Membrane VAD, as a first-of-its-kind pump prototype enabling physiological blood propulsion through the cyclic actuation of a hyperelastic membrane, enabling the protection from the thrombogenic interaction between blood and the implant materials. The centre of the luminal membrane surface displays a rationally-developed surface topography interfering with flow to support a living endothelium. The precast cell layer survives to a range of dynamically changing pump actuating conditions i.e., actuation frequency from 1 to 4 Hz, stroke volume from 12 to 30 mL, and support duration up to 313 min, which are tested both in vitro and in vivo, ensuring the full retention of tissue integrity and connectivity under challenging conditions. In summary, the presented results constitute a proof of principle for the Hybrid Membrane VAD concept and represent the basis for its future development towards clinical validation.

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          The online version of this article (10.1007/s10439-020-02590-1) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis.

          Intercellular junctions mediate adhesion and communication between adjoining endothelial and epithelial cells. In the endothelium, junctional complexes comprise tight junctions, adherens junctions, and gap junctions. The expression and organization of these complexes depend on the type of vessels and the permeability requirements of perfused organs. Gap junctions are communication structures, which allow the passage of small molecular weight solutes between neighboring cells. Tight junctions serve the major functional purpose of providing a "barrier" and a "fence" within the membrane, by regulating paracellular permeability and maintaining cell polarity. Adherens junctions play an important role in contact inhibition of endothelial cell growth, paracellular permeability to circulating leukocytes and solutes. In addition, they are required for a correct organization of new vessels in angiogenesis. Extensive research in the past decade has identified several molecular components of the tight and adherens junctions, including integral membrane and intracellular proteins. These proteins interact both among themselves and with other molecules. Here, we review the individual molecules of junctions and their complex network of interactions. We also emphasize how the molecular architectures and interactions may represent a mechanistic basis for the function and regulation of junctions, focusing on junction assembly and permeability regulation. Finally, we analyze in vivo studies and highlight information that specifically relates to the role of junctions in vascular endothelial cells.
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            Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure

            In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure.
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              The Society of Thoracic Surgeons Intermacs 2019 Annual Report: The Changing Landscape of Devices and Indications

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                Author and article information

                Contributors
                aldo.ferrari@empa.ch
                falk@dhzb.de
                mazza@imes.mavt.ethz.ch
                Journal
                Ann Biomed Eng
                Ann Biomed Eng
                Annals of Biomedical Engineering
                Springer International Publishing (Cham )
                0090-6964
                1573-9686
                8 September 2020
                8 September 2020
                2021
                : 49
                : 2
                : 716-731
                Affiliations
                [1 ]GRID grid.5801.c, ISNI 0000 0001 2156 2780, Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, , ETH Zurich, ; Sonneggstrasse 3, 8092 Zurich, Switzerland
                [2 ]GRID grid.418209.6, ISNI 0000 0001 0000 0404, Department of Cardiothoracic and Vascular Surgery, , German Heart Institute Berlin, ; Berlin, Germany
                [3 ]GRID grid.7354.5, ISNI 0000 0001 2331 3059, EMPA, Swiss Federal Laboratories for Material Science and Technologies, ; Überlandstrasse 129, 8600 Dübendorf, Switzerland
                [4 ]GRID grid.5801.c, ISNI 0000 0001 2156 2780, Institute for Mechanical Systems, ETH Zurich, ; 8092 Zurich, Switzerland
                [5 ]GRID grid.7836.a, ISNI 0000 0004 1937 1151, Christiaan Barnard Division of Cardiothoracic Surgery, , University of Cape Town, ; Cape Town, South Africa
                [6 ]GRID grid.5801.c, ISNI 0000 0001 2156 2780, Laboratory of Composite Materials and Adaptive Structures, , ETH Zurich, ; 8092 Zurich, Switzerland
                [7 ]GRID grid.5801.c, ISNI 0000 0001 2156 2780, Product Development Group Zurich, Department of Mechanical and Process Engineering, , ETH Zurich, ; Zurich, Switzerland
                [8 ]GRID grid.6363.0, ISNI 0000 0001 2218 4662, Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité – Universitätsmedizin, ; Berlin, Germany
                [9 ]GRID grid.7400.3, ISNI 0000 0004 1937 0650, Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, , University of Zurich, ; Zurich, Switzerland
                [10 ]GRID grid.6363.0, ISNI 0000 0001 2218 4662, Department of Cardiovascular Surgery, , Charité - Universitätsmedizin Berlin, ; Berlin, Germany
                [11 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, Deutsches Zentrum für Herz-Kreislaufforschung, ; Standort Berlin, Germany
                [12 ]GRID grid.5801.c, ISNI 0000 0001 2156 2780, Translational Cardiovascular Technologies, Institute of Translational Medicine, Department of Health Sciences and Technology, , Swiss Federal Institute of Technology (ETH), ; Zurich, Switzerland
                Author notes

                Associate Editor Tingrui Pan oversaw the review of this article.

                Author information
                http://orcid.org/0000-0002-6411-8871
                Article
                2590
                10.1007/s10439-020-02590-1
                7851026
                32901382
                bf11db89-0ea4-4775-b0ca-50840faba780
                © The Author(s) 2020

                Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 February 2020
                : 11 August 2020
                Categories
                Original Article
                Custom metadata
                © Biomedical Engineering Society 2021

                Biomedical engineering
                vad,endothelialization,wall shear stress,wall deformation,hyperelastic membrane

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