Zhao, Joseph Junjie; (2019) A Nanometre Scale Surface Coating to Promote Endothelization of Intracranial Stents. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

INTRODUCTION: Stroke is the leading cause of disability worldwide and a major cause of death, its mortality is second only to cardiovascular disease. The role of intracranial stents is essential in the management of stroke, but current intracranial stents display unwanted side effects resulting in allergic reactions, chronic inflammation and thrombosis followed by re-narrowing of the blood vessels. Surface modification strategies are now in demand to improve tissue interactions at the neurovascular interface. This study aims to develop a novel nano-surface coating technique to create reproducible nano-metric scale surface topographies and to apply it as a post-modification of intracranial stents, to promote in-situ endothelization. METHODOLOGY: We develop a low-cost procedure to create polymeric nanoisland coating by enduring phase separation. SEM and AFM were applied to study the topography profile of the coating. Hemocompatibility tests were performed to assess the thrombogenicity of the coating. HUVECs were also cultured on the coating to assess the toxicity and biocompatibility of the coating. SEM was carried out on the cells after culturing on the coatings to reveal the material-cellular interaction on the coating surface. Coating procedure was then optimised to be applied onto bare metal stents (BMSs). The coated BMSs were mounted onto balloon catheters, sterilised with Ethylene Oxide and implanted into a pilot rabbit model for 28-days. Patency data was collected, histological analyses were then performed following termination. RESULTS: SEM and AFM confirmed the presence of a uniform coating layer with nano-islands of 20 nm in height and 100 nm in radius. Hemocompatibility tests revealed the coating was inert towards human blood component and showed lower thrombogenicity than control. HUVECs also demonstrated enhanced growth and proliferation on the coating. SEM morphology study hinted that the nano-islands on the coating could be promoting the HUVECs migration and growth by providing contact guidance to the cells. We successfully apply the coating onto commercially available BMSs. Delamination study revealed only minimal surface cracks on the optimised coated BMSs, suggesting the coating remained stable. Finally, two coated BMSs were implanted into two healthy New Zealand White rabbits, and their patency was maintained over 28 days. CONCLUSION: We have developed a simple and reproducible polymeric nano-island coating that showed low thrombogenicity and promote in-situ endothelization for vascular stents. Preliminary in vivo data suggest non-inferior early patency compared to uncoated BMSs with no apparent adverse effect.

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