Titanium Dioxide Nanotube Arrays for Cardiovascular Stent Applications.

Ita Junkar,Janez Kovač,Metka Benčina,Katja Lakota,Mukta Kulkarni,Katjuša Mrak-Poljšak,Snežna Sodin-Šemrl,Aleš Iglič,Miran Mozetič

doi:10.1021/acsomega.9b04118

Abstract

Efficient stent implantation among others depends on avoiding the aggregation of platelets in the blood vessels and appropriate proliferation of endothelial cells and controlled proliferation of smooth muscle cells, which reduces the development of pathology, such as neointimal hyperplasia, thrombosis, and restenosis. The current article provides an elegant solution for prevention of platelet and smooth muscle cell adhesion and activation on stent surfaces while obtaining surface conditions to support the growth of human coronary artery endothelial cells. This was achieved by surface nanostructuring and chemical activation of the surface. Specific nanotopographies of titanium were obtained by electrochemical anodization, while appropriate chemical properties were attained by treatment of titanium oxide nanotubes by highly reactive oxygen plasma. Surface properties were studied by scanning electron microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. Wettability was evaluated by measuring the water contact angle. The influence of nanostructured morphology and plasma modification on in vitro biological response with human coronary artery endothelia and smooth muscle cells as well as whole blood was studied. Our results show that a combination of nanostructuring and plasma modification of the surfaces is an effective way to achieve desired biological responses necessary for implantable materials such as stents.

Highlights

Characteristics of titanium and titanium alloys, such as high biocompatibility, corrosion resistance to body fluids, great tensile strength and flexibility have ensured their and extensive use as biomaterials
Placement of bare metal stent (BMS) in the blood vessel is connected with mechanical injuries of the lumen wall, which initiates a variety of reactions, including platelet activation and thrombus formation, accompanied by inflammation, and proliferation and migration of smooth muscle cells within the media and the intima.[1,2]
The morphology of the obtained TiO2 NTs was evaluated by scanning electron microscopy (SEM) and atomic force microscopy (AFM)

Summary

Introduction

Characteristics of titanium and titanium alloys, such as high biocompatibility, corrosion resistance to body fluids, great tensile strength and flexibility have ensured their and extensive use as biomaterials. Titanium alloys are extensively used for stent application, they still lack desired biological responses, mostly due to restenosis and thrombosis. Restenosis still presents a huge problem on all stent surfaces. Placement of bare metal stent (BMS) in the blood vessel is connected with mechanical injuries of the lumen wall, which initiates a variety of reactions, including platelet activation and thrombus formation, accompanied by inflammation, and proliferation and migration of smooth muscle cells within the media and the intima.[1,2] All these cellular responses lead to thickening of the intima by smooth muscle cells and surrounding extracellular matrix with or without progression to restenosis. Drug-eluting stents (DES) with various coatings were employed to cut high restenosis rates of BMS. The thrombogenicity and restenosis induction of blood-connecting devices remain a serious concern and should be given a great deal of attention in order to fabricate surfaces with improved tissue-material response

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