Background and Objective Notwithstanding the widespread implementation of flow diverters (FDs) in the treatment of intracranial aneurysms, the exact mechanism of action of these devices remains elusive. The aim of this study is to advance the understanding of cellular responses to FD implantation using a 3D tissue engineered in vitro aneurysm model.

Methods Aneurysm-like blood vessel mimics (aBVMs) were constructed by first electrospinning polycaprolactone nanofibers on desired aneurysm-like geometries to create scaffolds. After conditioning, aBVMs were mounted into sterile bioreactor chambers and incubated with a cell culture media under steady state flow. Then aBVMs were sodded with human carotid smooth muscle cells (SMCs) followed by endothelial cells (ECs). Then, appropriately sized FDs (Pipeline Embolic Device, Medtronic, CA) were deployed in the parent vessel of aBVMs under fluoroscopic guidance, covering the neck. AVBMs with implanted flow diverters were cultivated for 7, 14 or 28 days (n=3 for each time point). En face immunofluorescence imaging of the aBVMs was performed for EC and SMC markers. The cell coverage in the neck was measured semi-quantitatively.

Results The mean diameter of the parent vessel of aBVMs was 4.50 mm. The mean neck diameter, width, and height were 6 mm, 5.0 mm, 5.0 mm, respectively. The device segment in the parent artery was completely endothelialized at 7 days. The majority of device struts, but not the pores between struts, at the parent artery and the neck interface were partially covered with ECs and SMCs. The device struts in the middle of the neck were lacking cell coverage. At 14 days, histology verified that a neointimal lining like human tissue had formed coverage. Translucent tissue islands partially covering both the struts and pores in the center of the neck were observed. Almost the entire necks of aBVMs were covered with translucent neointimal layer at 28 days. A higher degree of cellular coverage was seen on the struts and pores at the neck at 28 days compared to both 7 and 14 days.

Conclusion Implantation of FDs in the tissue engineered aneurysm model simulates the cellular responses demonstrated in the experimental rabbit model. ABVMs would be a valuable alternative tool for evaluating the healing mechanisms of endovascular aneurysm devices.

Disclosures W. Liu: None. D. Ding: None. Y. Ding: None. K. Temnyk: None. T. Shen: None. K. O’Halloran Cardinal: None. D. Kallmes: None. R. Kadirvel: 1; C; NIH grant# NS076491.