Nanosurface modification of titanium and titanium coated stainless steel coronary stents for preferential cell functions

Surface modification of metallic implants is proposed as a viable means to alleviate the problems related to in-stent restenosis. Amongst the various surface modification strategies, surface nanotexturing is highlighted as a promising approach to improve the cellular behavior and tissue integration of biomedical implants. This thesis work focuses on developing a polymer-less and drug-free nanostructured coating on coronary stents to promote the natural growth of an intact, functional endothelium which could serve as a smooth barrier, preventing platelet aggregation and proliferation of smooth muscle cells and thereby addressing the issue of in-stent restenosis. To demonstrate this, as a first step, an array of unique, integrated TiO2 nanostructures of distinct morphologies viz., Nanoleaves, Nanopores, and Nanorods were developed on metallic titanium (Ti) surfaces using a simple, aqueous chemistry based hydrothermal route. Influence of various surface nanotopographies on the proliferation and functionality of vascular endothelial and smooth muscles cells were investigated in-vitro. Nanostructuring resulted in significantly enhanced cellular viability and proliferation of endothelial cells, with raised levels of nitric oxide and substantially decreased smooth muscle cell proliferation. To propose this strategy of surface modification for translation on to clinically used metallic stents, it is imperative that the surface be also hemocompatible an essential attribute for any blood contacting device. Direct blood interaction studies of TiO2 nanostructures of varied morphologies on contact with human blood was carried out in-vitro, and also after endothelialisation of the substrate, to study the influence of endothelial layer on blood components. Hemocompatibility was also evaluated under dynamic flow conditions in an in-vitro circulation model using nanostructured stent prototypes. Nanomodified surfaces showed negligible hemolysis, insignificant thrombus formation with no alterations in the normal clotting times, and minimal inflammatory