Development and evaluation of a nanometer-scale hemocompatible and antithrombotic coating technology for commercially available intracranial stents and flow diverters

An intracranial aneurysm is a local dilation of an artery in the cerebral circulation. While the etiology of intracranial aneurysms is unknown, they likely result from a combination of factors including the weakening and degeneration of the collagen fibers and the internal elastic lamina comprising the arterial wall, as well as hemodynamic-associated stress resulting from blood pulsation inside the aneurysm sac. Intracranial aneurysm rupture leads to a devastating sequela, as 50% of patients die. In the U.S. alone there are approximately 30,000 cases of subarachnoid hemorrhage annually, a prevalence which has pushed practitioners to aggressively treat the aneurysm disease. Traditionally, intracranial aneurysms were managed with open craniotomy and microsurgical clipping; however, these treatment modalities carry relatively high morbidity and mortality depending upon the aneurysm location and surgical experience. In 2002 the International Subarachnoid Hemorrhage Aneurysm Trial established the superiority of the endovascular coiling of intracranial aneurysms compared to microsurgical clipping. This trial led to a paradigm shift in treating intracranial aneurysms with marked use of intracranial stenting, including devices used to assist endovascular coiling and stand-alone flow diverting devices. However, the placement of intracranial devices in the cerebral circulation mandates the adjunctive application of dual anti-platelet pharmaceuticals to minimize thromboembolic events, despite being associated with increased patient risk. This dissertation proposes a novel multilayer, nanometer-scale coating technology suitable for commercially available intracranial stents and flow diverting devices to minimize the use of dual anti-platelet therapy in the elective setting and expand the use of intracranial devices in the acute setting of ruptured intracranial aneurysms. A combination of qualitative and quantitative chemical characterization techniques was used to assess the composition, uniformity, and thickness of each coating layer on commercially available flow diverting devices; overall the coating was found to be relatively uniform and conformal to the device wires. Furthermore, in-vitro and in-vivo testing on commercially available intracranial devices suggest some hemocompatible and antithrombotic properties. Finally, the proposed coating technology can be modified for use as a platform for the attachment of FDA-approved molecules. With further optimization and testing this technology has the potential to minimize the adjunctive use of dual-antiplatelet therapy in the endovascular treatment of intracranial aneurysms.