Tissue-engineered aneurysm models for in vitro assessment of neurovascular devices.

Abstract

Preclinical testing of neurovascular devices is crucial for successful device design and is commonly performed using in vivo organisms such as the rabbit elastase-induced aneurysm model; however, simple in vitro models may help further refine this testing paradigm. The purpose of the current work was to evaluate, and further develop, tissue-engineered blood vessel mimics (BVMs) as simple, early-stage models to assess neurovascular devices in vitro prior to animal or clinical use. The first part of this work used standard straight-vessel BVMs to evaluate flow diverters at 1, 3, and 5 days post-deployment. The second part developed custom aneurysm-shaped scaffolds to create aneurysm BVMs. Aneurysm scaffolds were characterized based on overall dimensions and microstructural features and then used for cell deposition and vessel cultivation. It was feasible to deploy flow diverters within standard BVMs and cellular linings could withstand and respond to implanted devices, with increasing cell coverage over time. This provided the motivation and foundation for the second phase of work, where methods were successfully developed to create saccular, fusiform, and blister aneurysm scaffolds using a wax molding process. Results demonstrated appropriate fiber morphology within different aneurysm shapes, consistent cell deposition, and successful cultivation of aneurysm BVMs. It is feasible to use tissue-engineered BVMs for assessing cellular responses to flow diverters, and to create custom aneurysm BVMs. This supports future use of these models for simple, early-stage in vitro testing of flow diverters and other neurovascular devices.