Project Summary/Abstract Subarachnoid hemorrhage (SAH) is a devasting acute neurological disease that remains a major cause of premature mortality. SAH is most caused by incidental rupture of an intracranial aneurysm (ICA). The mortality rate of aneurysm rupture can reach as high as 40% within the first week of incidence. Even if the aneurysm is treated in a timely manner, the chance of moderate to severe brain damage is 20-35%. Endovascular coil embolization is the current gold-standard, minimally invasive therapy of ICAs; however, emerging clinical challenges of coil embolization are unsatisfactory aneurysm recurrence rates: ~44% by 5-6 years after the initial coil therapy (of which more than 50% requiring re-treatment), and suboptimal complete occlusion, especially for treating wide-necked ICAs and/or aneurysms with a complex 3D geometry. Thus, there is a need for a durable device to treat unruptured ICAs that targets patient-specific aneurysms and intra-aneurysmal circulation and provides long-lasting complete occlusion. Our research objectives of this project are to: 1) design and fabricate personalized embolic devices for treating saccular, bifurcated IACs using additive manufacturing and a combined experimental/biomechanical approach, and 2) provide a holistic biomechanical and hemodynamic comparison between our device and other selected endovascular embolic techniques. This proposal builds upon the assembled preliminary data, and leverages Dr. Lee’s experience with tissue biomechanics and in-silico modeling, in collaboration with polymer science and additive manufacturing researchers at the University of Oklahoma, clinical and neurosurgical expertise of clinicians at Indiana University – Medicine, and micro-device and catheter expert at Purdue. Specifically, we propose to design, develop, and evaluate patient-specific SMP embolic devices using 3D printing-based polymer fabrication. Our embolic devices are designated to target personalized aneurysm filling and maximize the rate of long-lasting complete occlusion. Next, through in-vitro flow loop testbed and in-vivo small animal studies, the efficacy and aneurysm occlusion of our personalized embolic devices will be systematically evaluated in comparison to the clinical gold standard as well as three other contemporary embolic methods. The endpoint of this project will be a cutting-edge solution for ICA embolization, that uses fundamental information on aneurysms based on holistic biomechanical and hemodynamic analyses – allowing individual-optimized aneurysm filling to achieve immediate & long-term complete occlusion and reduce aneurysm recurrence. Collectively, our developments will serve as a logical first step toward attaining our long- term goal to advance the state of the art in translational medicine by facilitating personalized, preventive management of unruptured ICAs and reduce aneurysm rupture-induced hemorrhagic strokes.