Stroke and atherosclerotic cerebrovascular disease occurs in approximately 9% of the population worldwide and nearly 75% of all strokes occur in persons over 65 years. Approximately 30% of the stroke patients have been attributed to atherosclerotic carotid artery stenosis. While current endovascular therapies for carotid artery stenosis show feasibility and safety, they require multiple steps such as balloon angioplasty and placement of stents with the separate embolic protection filter devices. Therefore, a critical need exists for developing endovascular technology to treat carotid artery stenosis that is simple, safe and effective without additional placement of filter devices (i.e., emboli-protection "filter" device) during the procedure. One example would be an embolic protection stent covered with ultra-thin micro-patterned membrane (i.e., covered stent graft) on bare metal stents. Advancements in stent graft technologies for carotid artery stenosis are limited by the lack of a suitable, biocompatible material for the covering of the embolic protection stent. The availability of an appropriate, thrombus resistant material for endovascular devices could lead to significant improvements in the overall mortality and morbidity of strokes induced by carotid artery stenosis. The University of Pittsburgh has developed a novel micro-patterned thin film nitinol (TFN) covered stent. We have also developed a unique process that can produce superhydrophilic and thrombus resistant TFN. It is our hypothesis that this newly developed device containing the micro-patterned TFN membrane can produce endografts which is ultra-low profile and decrease the risk of embolization during/after carotid artery stenting. In additio, the unique surface qualities of this material will provide a substantial reduction in stent thrombosis and neointima growth in the treatment of carotid artery stenosis. This proposal outlines a plan for research and development of a novel thin film nitinol covered carotid artery embolic protection stent that is non-thrombogenic and ultra-low profile, as well as capable of continuously preventing intra-/post-operative distal embolization. Problems and complications associated with current carotid artery stenosis treatment procedures, as well as the need and usefulness of low profile, non- thrombogenic, micro-patterned TFN covered stents are discussed. A fundamental in vitro static biocompatibility studies are proposed to demonstrate superior in cytotoxicity, cell growth behavior, and thromboresistance of the negatively-charged superhydrophilic TFN surface. A novel design which prevents the dislodgement of thrombosis or cholesterol from the vascular wall will be studied with structural modeling tools (i.e., finite element solution and computer aided design software). Subsequently, a two-stage fabrication scheme (to be carried out at University of Pittsburgh Nano/Microfabrication facilities and Biomanufacturing-Vascular Device Laboratory) is proposed. The first stage of the design incorporates a micro-patterned TFN with a commercially available bare metal stent. The second stage of the design collapses the whole device into delivery catheters (e.g.,5.0Fr), showing collapsibility and compatibility of the device with existing delivery catheters. A novel i vitro apparatus for the efficacy of the device using an artificial emboli and biodegradable polymer coating in microfluidic devices is presented in order to show how the device design provides optimal dimension and geometry of micro pores in TFN graft membrane. The in vitro apparatus is proposed to quantitatively measure the detached micro particles (i.e., artificial emboli) with the various micro-patterned TFN graft membrane.
Stroke and atherosclerotic cerebrovascular disease occurs in approximately 9% of the population worldwide and approximately 30% of them have been attributed to carotid artery stenosis. The biggest hurdle for medical devices used in the treatment of carotid artery stenosis is embolization, which is blood clots or cholesterol fragments develop and enter the cerebral circulation during and after the procedure. To solve this problem, University of Pittsburgh has developed a new device that in preliminary studies demonstrates thromboresistance, minimal neointima growth, ultra-low profile feature, and versatile capability to micro-machining, and thus is ideally suited for treating carotid artery stenosis, ultimately prevents stroke.