de Mel, A.; (2011) Bio-functionalisation of a nanocomposite based coronary artery bypass graft; conferring heamocompatibility. Doctoral thesis , UCL (University College London).

Abstract

Coronary artery bypass surgery is a life saving surgical solution for patients presented with greater than 70% occluded or stenosed arteries. For these patients, autologous vein is the graft of choice. Alarmingly, 5-30% of patients have no suitable veins available due to previous use or diseased vein wall, thus the critical clinical need for nonthrombogenic vascular grafts is underscored. Our group has synthesised and patented a nanocomposite polymer based on polyhedral oligomeric silsesquioxane modified polycarbonate urea-urethane (POSS-PCU) nanocomposite polymer. The polymer was extruded using coagulation technique to match mechanical properties of a native artery. Optimising the interactions with blood on the graft surface is of keen interest. Endothelialisation is a favourable solution for enhancing antithrombogenic properties. The protective effect of the endothelium is recognised to be governed by nitric oxide (NO). A graft designed for in-situ endothelialisation will have an interval, where it will be prone to platelet adhesion before complete endothelialisation. Therefore it is desirable to induce antithrombogenic properties during this initial period and the induction of NO is desirable. In this study, current research on biofunctionalisation of biomaterials to enhance antithrombogenic properties by inducing in-situ endothelialisation and NO release were reviewed. The possibility of biofunctionalisation of POSS-PCU polymer whilst retaining its original polymer chemistry was investigated by using amine functionalised nanoparticles including POSS and fumed silica to anchor bioactive peptides (RGD) and amino acids (larginine). The antithrombogenic properties of the biofunctionalised polymer were demonstrated to be due to NO release and endothelialisation. The biofunctionalised polymer was exposed to whole blood, endothelial progenitor cells and platelets. Overall this study presents a novel method of biofunctionalising vascular bypass grafts to induce endothelialisation as tested in a bioreactor and also a means of exploiting the possibility of adhesion of platelets to induce NO synthesis. Overall I aimed to look into methods of functionalising graft surface to induce nitric oxide synthesis when the graft is implanted and is in contact with blood.

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