Nanosurface engineering of bare metal coronary stents for reduction of in stent restenosis

Abstract

Recent progresses in coronary stents have all been particularly focused towards directing endothelial cells (ECs) and smooth muscle cells (SMCs), potentially via alterations in surface topographical cues, for improving the efficacy of vascular implants. This perspective was already proven by our group on hydrothermally modified nanotextured metallic titanium (Ti), wherein a preferential vascular cell response was noted on nanosurfaces in-vitro. In this work, bare metal stents (BMSs) of stainless steel (SS) and cobalt-chromium (CC) were surface engineered to develop nanoscale titania topography using a combination of physical vapor deposition and thermochemical processing and the impact of these nanotextured stents in modulating vascular cell response in-vitro and in-vivo were evaluated, using titania coated stents without nanotopography and commercial drug eluting stents (DESs) as controls. The nanoleafy architecture developed on the stent surface retained its stability and was adherent upon repeated crimping and expansion, as well as under flow. This titania nanoengineered stent showed a preferential proliferation of ECs over SMCs in-vitro, which is an essential prerequisite for improving the in-vivo endothelialization, with simultaneous reduction of intimal hyperplasia. Interestingly, only the surface with nanotopography promoted a preferential cell response invitro as against the titania coated and bare surfaces. This can be ascribed to the differences in surface roughness, hydrophilicity and topography of nanotextured surfaces, which in turn reflected in the differences in cellular adhesion, proliferation and focal contact formations for ECs and SMCs. The efficacy of this surface-modified stent was assessed after implantation in rabbit iliac arteries for 8 weeks. This simple and easily scalable nanosurface modification strategy on metallic stents devoid of any drugs or polymers, could by itself foster rapid reendothelialization without excessive neointimal hyperplasia, thereby reducing in-stent restenosis..