title: Novel heart valve prosthesis with self-endothelialization potential made of modified polyhedral oligomeric silsesquioxane-nanocomposite material.
abstract: In the cardiovascular system, the endothelial layer provides a natural antithrombogenic surface on the inner portion of the heart and associated vessels. For a synthetic material therefore, the ability to attract and retain endothelial or endothelial progenitor cells (EPCs), ultimately creating a single endothelial layer on its surface, is of prime importance. The authors have developed a nanocomposite polymer, based on a combination of polyhedral oligomeric silsesquioxane nanoparticles and polycarbonate urea urethane (POSS-PCU), which is biocompatible and has been used in human for the world's first synthetic trachea, tear duct, and bypass graft. In this study, the authors modified the surface of this casted nanocomposite by grafting fibronectin derived bioactive peptides [glycine-arginine-glycine-aspartic acid-glycine (GRGDG) and lauric acid conjugated GRGDG (GRGDG-LA)] to enhance the endothelialization for using heart valves leaflets from circulating EPCs. Human peripheral blood mononuclear cells were separated using Ficoll-Paque centrifugation, with harvested EPCs purified using CD34 microbead labeling and magnetic-activated cell sorting. Cells were seeded onto 96 well plates coated with POSS-PCU, GRGDG/GRGDG-LA modified POSS-PCU and PCU polymers, for a period of 21 days. Cells were studied under light, confocal, and scanning electron microscope (SEM). Fluorescence-activated cell sorting was used to analyze cell surface markers. Cell attachment and proliferation was observed in all POSS-PCU samples, significantly higher than the activity seen within the control PCU polymers (p < 0.05). Microscopic examination revealed clonal expansion and morphological changes in cells seeded on POSS-PCU. The cells expressed increasing levels of mature endothelial cell markers over time with a concurrent reduction in hematopoietic stem cell marker expression. SEM showed a mixed population of morphologically differentiated endothelial cells and EPCs. These results support the use of heart valve made with the POSS-PCU polymer and demonstrate that suitable chemical modification of this nanocomposite could increase self-endothelialization potential and reduce associated thrombotic events.
authors.affiliation: Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Sciences, University College London, London NW3 2QG, United Kingdom and Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran 14177-55469, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Ghanbari
authors.affiliation: UCL Medical School, University College London, London WC1E 7JE, United Kingdom.
authors.forename: Dina
authors.initials: D
authors.lastname: Radenkovic
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran 14177-55469, Iran and Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London NW3 2QG, United Kingdom.
authors.forename: Sayed Mahdi
authors.initials: SM
authors.lastname: Marashi
authors.affiliation: Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Sciences, University College London, London NW3 2QG, United Kingdom.
authors.forename: Shirin
authors.initials: S
authors.lastname: Parsno
authors.affiliation: GlaxoSmithKline, London Weybridge KT13 0DE, United Kingdom.
authors.forename: Nima
authors.initials: N
authors.lastname: Roohpour
authors.affiliation: Department of Mechanical Engineering, University College London, London WC1E 7JE, United Kingdom.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Burriesci
authors.affiliation: Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Sciences, University College London, London NW3 2QG, United Kingdom and NanoRegMed, Ltd., London EC1V 4PW, United Kingdom.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
mesh_terms: D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000502:physiology*; D066026:Endothelial Progenitor Cells / Q000502:physiology; D005434:Flow Cytometry; D006350:Heart Valve Prosthesis; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D008853:Microscopy; D053761:Nanocomposites; D009842:Oligopeptides; D017646:Organosilicon Compounds
chemical_list: C512088:1,3-bis(1,1,3,3,5,5-hexaethoxy-1,3,5-trisilacyclohexyl)propane; D008565:Membrane Proteins; D009842:Oligopeptides; D017646:Organosilicon Compounds; C000610393:POSS-PCU polymer