Custom tissue engineered aneurysm models with varying neck size and height for early stage in vitro testing of flow diverters

Abstract

Endovascular techniques for treating cerebral aneurysms are rapidly advancing and require testing to optimize device configurations. The purpose of this work was to customize tissue-engineered aneurysm “blood vessel mimics” (aBVMs) for early stage in vitro assessment of vascular cell responses to flow diverters and other devices. Aneurysm scaffolds with varying neck size and height were created through solid modeling, mold fabrication, mandrel creation, and electrospinning. Scaffold dimensions and fiber morphology were characterized. aBVMs were created by depositing human smooth muscle and endothelial cells within scaffolds, and cultivating within perfusion bioreactors. These vessels were left untreated or used for flow diverter implantation. Cellular responses to flow diverters were evaluated at 3 days. Custom scaffolds were created with aneurysm neck diameters of 2.3, 3.5, and 5.5 mm and with aneurysm heights of 2, 5, and 8 mm. A set of scaffolds with varying neck size was used for aBVM creation, and dual-sodding of endothelial and smooth muscle cells resulted in consistent and confluent cellular linings. Flow diverters were successfully implanted in a subset of aBVMs, and initial cell coverage over devices was seen in the parent vessel at 3 days. Direct visualization of the device over the neck region was feasible, supporting the future use of these models for evaluating and comparing flow diverter healing. Tissue-engineered aneurysm models can be created with custom neck sizes and heights, and used to evaluate cellular responses to flow diverters and other endovascular devices.