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.

Endothelialized silicone aneurysm models for in vitro evaluation of flow diverters

“… 6 7 9 10 Electrospinning is limited in its ability to create certain complex geometries, especially saccular necks with tight angles. 14 Silicone is non-degradable and stable for a longer time, as compared with degradable polymers often used in electrospinning. Additionally, silicone is transparent in comparison with opaque electrospun polymers, which allowed for very straightforward deployment through purely visual placement.…”

“…These components could be partially addressed through incorporation of more cell types and customized bioreactor flow circuits. For example, previous work has incorporated both endothelial cells and smooth muscle cells within in vitro aneurysm models, 14 and physiologic flow environments have been incorporated in other in vitro models. 10 Including more physiologic flow in this model would allow assessments of the interaction between wall shear stresses and device healing.…”

“…Many laboratories also do not have in-house customizable electrospinning capabilities such as those previously published. 14 Given the extensive use of silicone models in the neurovascular field and the ability to create complex clinical geometries, silicone aneurysm models could be effective in vitro models if they supported consistent formation of endothelial cell linings and, importantly, if those cell linings could withstand device deployment. Previous work has shown the ability to endothelialize PDMS models, 9 10 but assessment beyond 24 hours and the ability to use these types of models for device testing has not been shown.…”