Cerebral aneurysms occur due to the ballooning of blood vessels in the brain. Rupture of aneurysms can cause a subarachnoid hemorrhage, which, if not fatal, can cause permanent neurologic deficits. Minimally invasive neurovascular devices, such as embolization coils and flow diverters, are methods of treatment utilized to prevent aneurysm rupture. The rapidly growing market for neurovascular devices necessitates the development of accurate aneurysm models for preclinical testing. In vivo models, such as the rabbit elastase model, are commonly chosen for preclinical device testing; however, these studies are expensive, and aneurysm geometries are difficult to control and often do not replicate the variety of geometries found in clinical cases. A promising alternative for preclinical testing of neurovascular devices is an aneurysm blood vessel mimic (aBVM), which is an in vitro tissue-engineered model of a human blood vessel composed of an electrospun scaffold with an aneurysm geometry and human vascular cells. Previous work in the Cal Poly Tissue Engineering Lab has established a process for creating different aneurysm scaffolds based on the shape of different geometries, and this work aimed to further advance these aneurysm geometries in order to enhance the versatility of the in vitro model.
The overall goal of this thesis was to customize the aBVM model through variations of different dimensions and to validate the scaffold variations for neurovascular device testing. First, a literature review was performed to identify critical ranges of aneurysm neck diameters and heights that are commonly seen in rabbit elastase models and in human clinical settings in order to set a foundation for creating new geometries. Based on the results, aneurysm geometries with varying neck sizes and heights were modeled and molded, and scaffolds were fabricated through electrospinning. Methods were developed to characterize scaffolds with internal measurements through imaging techniques using a scanning electron microscope. To validate these scaffolds for use as aBVMs for neurovascular device testing, constructs were created by dual-sodding human endothelial cells and smooth muscle cells into scaffolds with varying neck sizes. Finally, flow diverters were deployed in constructs with varying neck sizes in order to evaluate feasibility and initial healing. Customized aneurysm scaffolds can eventually be used with a variety of device studies for screening of neurovascular devices or as a predecessor for in vivo preclinical testing.
| Identifer | oai:union.ndltd.org:CALPOLY/oai:digitalcommons.calpoly.edu:theses-3509 |
| Date | 01 August 2019 |
| Creators | Villadolid, Camille D. |
| Publisher | DigitalCommons@CalPoly |
| Source Sets | California Polytechnic State University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Master's Theses |
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