title: Nitric oxide-eluting nanocomposite for cardiovascular implants.
abstract: Cardiovascular implants must resist thrombosis and intimal hyperplasia, but they are prone to such patency limiting conditions during graft implantation and prior to endothelialisation. Nitric oxide (NO) released from the endothelium has a complex protective role in the cardiovascular system, and this study has addressed: (1) in situ NO release profiles from S-nitrosothiols ((S-Nitroso-N-acetylpenicillamine (SNAP) and (S-Nitrosoglutathione (GSNO)) incorporated into polyhedral oligomeric silsesquioxanepoly(carbonate-urea)urethane (POSS-PCU) coronary artery bypass grafts (CABG) in a physiological pulsatile flow, and (2) the determination of their interaction with endothelial progenitor cells (EPCs), smooth muscle cells, platelets, whole blood kinetics. It was found that 1, 2, and 3 wt% SNAP/GSNO incorporated into POSS-PCU-CABG successfully eluted NO, but optimal elution was evident with 2 %-SNAP-POSS-PCU. NO release determined under static conditions using the Griess assay, and in situ measurements under pulsatile flow using amperometric probe was found to differ, thus confirming the significance of monitoring NO-elution under haemodynamic conditions. 2 %-SNAP-POSS-PCU demonstrated anti-thrombogenic kinetics through thromboelastography measurements, while metabolic activity using Alamar Blue™ assay and scanning electron microscopy demonstrated greater adhesion of EPCs and reduced adhesion of platelets.
authors.affiliation: Centre for Nanotechnology & Regenerative Medicine, University College London, London, UK.
authors.forename: Achala
authors.initials: A
authors.lastname: de Mel
authors.forename: Noora
authors.initials: N
authors.lastname: Naghavi
authors.forename: Brian G
authors.initials: BG
authors.lastname: Cousins
authors.forename: Innes
authors.initials: I
authors.lastname: Clatworthy
authors.forename: George
authors.initials: G
authors.lastname: Hamilton
authors.forename: Arnold
authors.initials: A
authors.lastname: Darbyshire
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Seifalian
mesh_terms: D000327:Adsorption; D001807:Blood Vessel Prosthesis; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000737:chemistry; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019544:Equipment Failure Analysis; D006801:Humans; D008422:Materials Testing; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D053761:Nanocomposites / Q000737:chemistry* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011474:Prosthesis Design
chemical_list: D002316:Cardiotonic Agents; D053769:Nanocapsules; D009569:Nitric Oxide