Endothelial Responses to Curvature-Induced Flow Patterns in Engineered Cerebral Aneurysms.

Area of Science:

• Biomedical Engineering
• Fluid Dynamics
• Cell Biology

Background:

• Hemodynamic factors are critical in cerebral aneurysm outcomes.
• Computational fluid dynamics (CFD) models estimate endothelial mechanical environments.
• Previous studies correlated CFD with endothelial cell (EC) responses.

Purpose of the Study:

• To develop a workflow for generating anatomic-scale aneurysm models with EC cultures.
• To compare EC responses to flow profiles influenced by parent vessel curvature.
• To link CFD-derived wall shear stress (WSS) and WSS gradients (WSSG) to EC behavior.

Main Methods:

• Generated anatomic-scale aneurysm models.
• Established luminal cultures of ECs under physiological flow.
• Analyzed EC morphology and protein localization in response to flow patterns.

Main Results:

• Parent vessel curvature alters WSS and WSSG, impacting ECs.
• ECs in high WSS regions aligned with flow and showed Notch1-ECD polarization.
• Low WSS regions exhibited less EC alignment and attenuated Notch1-ECD polarization due to WSSG differences.

Conclusions:

• Engineered cellularized aneurysm models connect CFD to endothelial biology.
• Flow-induced WSS and WSSG influence EC morphology and protein localization.
• Findings advance understanding of endothelial cell-mediated cerebral aneurysm disease.