Naghavi, N; (2016) Development of nitric oxide eluting nanocomposite polymer for cardiovascular applications. Doctoral thesis , UCL (University College London).

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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) elution from healthy endothelium maintains haemostasis throughout the vasculature, and surgical devices that release NO are known as desirable treatment options. Polyhedral oligomeric silsesquioxane poly(carbonate-urea)urethane (POSS-PCU) nanocomposite polymer, developed in our laboratory, has already been fabricated in the form of bypass grafts, showing promising mechanical and biocompatible properties. NO donors have been passively incorporated within POSS-PCU; however, the study recognised a need for better donor retention and sustained NO release. Therefore, this thesis has focussed on utilising novel NO-eluting POSS-PCU bypass grafts with the aim to prepare materials that can release prolonged sustained levels of NO within physiological concentration range, with greater retention of the donor within the base polymer. Methods: POSS-PCU was functionalised with S-nitrosothiol NO donors using two modification methods including 1) covalent technique, and 2) using nanoparticles as delivery vehicles for NO donors. In addition, the importance of the analytical method for NO measurement was established through comparison of NO release from the grafts prepared via passive modification method using two different measurement techniques, which included amperometric and chemiluminescence. Each synthesis step in the preparation of NO-releasing polymer was extensively characterised and NO release properties studied. Finally, the biocompatibility of these materials was assessed. Results: It was established that chemiluminescence method detected NO at higher level than the amperometric technique. The two different synthesis methods resulted in the production of two types of nanocomposite polymer for the preparation of bypass grafts capable of NO release. Both modification techniques eliminated the problems associated with donor leaching observed with the non-covalently modified POSS-PCU. Incorporation of nanoparticles did not significantly change the elastic modulus of the original polymer, whereas covalently modified samples resulted in a significant change in the elastic modulus, as well as viscosity of POSS-PCU. Covalently modified grafts released NO at levels ranging from 1 – 24 pmol.cm-2 .min- 1 for a short time period of 6 h; however, the incorporation of different wt% of the nanoparticles into POSS-PCU resulted in higher flux of NO release which ranged from 2 to 85 pmol.cm-2 .min-1 for durations of 9 to 20 h. NO-releasing polymers showed less degree of clot formation and platelet adhesion/activation compared with the unmodified POSS-PCU, with nanoparticle conjugated samples showing greater anti-thrombogenic effects compared with the covalently modified samples. Conclusion: NO donor functionalisation within POSS-PCU enabled research on prolonging sustained NO release at physiologically relevant concentrations and enhanced the anti-thrombogenic properties of POSS-PCU. In addition, methods of determining NO level clearly demonstrated the relative difference between analysis techniques for case specific NO detection that can be applied to distinct experimental models associated with NO-eluting cardiovascular implants.

Type:	Thesis (Doctoral)
Title:	Development of nitric oxide eluting nanocomposite polymer for cardiovascular applications
Event:	UCL (University College London)
Language:	English
UCL classification:	UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > MAPS Faculty Office UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > MAPS Faculty Office > Institute for Materials Discovery
URI:	https://discovery.ucl.ac.uk/id/eprint/1502301

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