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Live-Cell In Vitro Aneurysm System using 3D Printing


Intracranial aneurysm (IA) rupture is a major health risk that often leads to permanent neurological damages and even death. Management of IAs has been challenging due to limited understanding of the underlying cellular mechanism of aneurysm progression. The endothelial cells have been known to play an important role in most vascular diseases. However, there has been a lack of understanding on how endothelial cells contribute to the pathogenesis of aneurysms. This study aims to develop an in vitro platform that will enable future studies of the effects of fluid mechanical environment on live endothelial cells by using 3D printing technology.

The elements of the flow environment, e.g., the velocity field and shear stress in an aneurysm, were simulated using computational fluid dynamics (CFD). These elements were then compared with those computed by particle image velocimetry (PIV) using the videos of tracers flown through a 3D printed aneurysm model. For live-cell experiments, the human umbilical vein endothelial cells (HUVECs) were cultured on the substrate in the area enclosed by the 3D printed aneurysms perfused at different flow rates. The results showed a region-specific pattern in HUVECs density that can be correlated to the fluid mechanical elements such as velocity field and shear stress. The cell density decreased significantly at the aneurysm proximal neck and belly regions, where shear stress is low with non-directional flow, and increased at the distal neck region, where shear stress is higher.

This study demonstrates the feasibility of a live-cell in vitro aneurysm model created using 3D printing. The development of this system with long-term live-cell culture in 3D printed aneurysm structures will enable future investigations to study the effects of fluid mechanical elements on endothelial cells. Such studies will contribute to better device design and clinical management for the aneurysm patients.

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