Enhanced Vascular Endothelial Cell Function on Nanostructured Titanium Surface Features: The Role of Nano to Submicron R
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Enhanced Vascular Endothelial Cell Function on Nanostructured Titanium Surface Features: The Role of Nano to Submicron Roughness Jing Lu, Dongwoo Khang, and Thomas J. Webster Division of Engineering and Department of Orthopaedic Surgery, Brown University, Providence, RI 02912, USA ABSTRACT To study the contribution of different surface feature properties in improving vascular endothelial cell adhesion, rationally designed nano/sub-micron patterns with various dimensions were created on titanium surfaces in this study. In vitro results indicated that endothelial cell adhesion was improved when the titanium pattern dimensions decreased into the nano-scale. Specifically, endothelial cells preferred to adhere on sub-micron and nano rough titanium substrates compared to flat titanium. Moreover, titanium with nano and sub-micron roughness and with the same chemistry as compared to flat titanium, had significantly greater surface energy. Thus, the present study indicated the strong potential of surface nanotopography and nano/sub-micron roughness for improving current vascular stent design. INTRODUCTION Coronary heart disease is one of the leading causes of deaths in the United States today. It affects more than 15 million Americans and results in over 400,000 deaths each year [1]. Among various treatments to coronary heart disease, vascular stenting is widely used because it can serve as a permanent implant in the human body. At present, titanium and Nitinol (titaniumnickel alloys), cobalt chromium alloys and stainless steel are major vascular stent materials [2-3] due to their suitable mechanical properties. Among them, titanium possesses excellent flexibility, dilatability, strength, and most importantly, biocompatibility. However, current vascular stents with conventional bare metals have the problem of severe in-stent restenosis due to the implantation process of such stents which can cause injury of the endothelium as well as extensive inflammatory responses [4]. Drug-eluting stents partially solve this problem. However, when deactivating immune cell functions, the immunosuppressant drugs embedded in the polymer coating also delay endothelialization at the same time, which leads to a high rate of late stage thrombosis. Therefore, accelerating endothelialization and reducing inflammatory responses simultaneously plays a critical role in designing future better vascular stents [5]. In this regard, bio-inspired nano-materials might provide a promising alternative for current drug-eluting vascular stents because nanotechnology might mimic the similar nanostructure of the natural blood vessel surface without any coating. To modify current stent surfaces, important properties such as topography, roughness and surface energy should be considered. For example, since endothelial cells align in the vascular, it can be argued that aligned or patterned nanosurfaces are better at increasing vascular cell functions than smooth surfaces [6-7]. Moreover, previous reports have been unclear towards the contribution of na
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