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.

A Material Conferring Hemocompatibility

“…For further study, an area of interest would be to examine the modification of L-AME release simultaneously with other known anti-thrombogenic molecules that influence the levels of NO, or endothelialization for further applications3031. Further work should also examine techniques such as the production of multi-layered polymers, or microencapsulation of molecules, to facilitate prolonged, sustained release of L-AME32.…”

“…Details of EPC extraction have been reported previously3055. Whole blood was obtained from healthy volunteers after signing an informed consent document accordance with the regulations and as approved by the local (Royal Free Hospital campus) ethics committee.…”

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“…Recent advances have been made in the field of POSS-PCU coronary artery grafts, where incorporation with S-nitrosothiols and consequent release of nitric oxide lead to superior graft patency, improved endothelization and resistance to thrombi formation [15]. Skin regeneration using stem cell based tissue engineering is not lagging behind.…”

Complexation of Amino‐Acid‐Based Block Copolymers With Dual Thermoresponsive Properties and Water‐Soluble Silsesquioxane Nanoparticles

“…In recent years, increasing attention has also been paid to developing silsesquioxane/biomolecule hybrids. [20][21][22][23][24][25][26][27] Recently, we developed novel smart amino acid-based polymer/silsesquioxane hybrids, in which the complexation of water-soluble silsesquioxane nanoparticles derived from 2-hydroxyethyl acrylate and poly( N -acryloyl-4-trans -hydroxy-L -proline), poly(A-Hyp-OH), can be manipulated by pH change in aqueous media. [ 28 ] Simple mixing of aqueous solutions of poly(A-Hyp-OH) and the silsesquioxane nanoparticles led to a straightforward formation of the pH-responsive hybrids, in which a white turbid dispersion was observed at pH = 5-8, whereas transparent solutions were obtained at pH = 2 and 10.…”