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Three-dimensional bioprinting of aneurysm-bearing tissue structure for endovascular deployment of embolization coils.

Biofabrication (2020-09-26)
Lindy Jang, Javier Alvarado, Marianna Pepona, Elisa Wasson, Landon Nash, Jason Ortega, Amanda Randles, Duncan Maitland, Monica Moya, William Frederick Hynes
ABSTRACT

Various types of embolization devices have been developed for the treatment of cerebral aneurysms. However, it is challenging to properly evaluate device performance and train medical personnel for device deployment without the aid of functionally relevant models. Current in vitro aneurysm models suffer from a lack of key functional and morphological features of brain vasculature that limit their applicability for these purposes. These features include the physiologically relevant mechanical properties and the dynamic cellular environment of blood vessels subjected to constant fluid flow. Herein, we developed three dimensionally (3D) printed aneurysm-bearing vascularized tissue structures using gelatin-fibrin hydrogel of which the inner vessel walls were seeded with human cerebral microvascular endothelial cells (hCMECs). The hCMECs readily exhibited cellular attachment, spreading, and confluency all around the vessel walls, including the aneurysm walls. Additionally, the in vitro devices were directly amenable to flow measurements via particle image velocimetry, enabling the direct assessment of the vascular flow dynamics for comparison to a 3D computational hydrodynamics model. Detachable coils were delivered into the printed aneurysm sac through the vessel using a microcatheter and static blood plasma clotting was monitored inside the aneurysm sac and around the coils. This biomimetic aneurysm in vitro model is a promising method for examining the biocompatibility and hemostatic efficiency of embolization devices and for providing hemodynamic information which would aid in predicting aneurysm rupture or healing response after treatment.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Pluronic® F-127, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Calcium chloride, anhydrous, granular, ≤7.0 mm, ≥93.0%
Sigma-Aldrich
Sodium hydroxide solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Gelatin from porcine skin, powder, gel strength ~300 g Bloom, Type A, BioReagent, suitable for electrophoresis, suitable for cell culture
Sigma-Aldrich
Fibrinogen from bovine plasma, Type I-S, 65-85% protein (≥75% of protein is clottable)
Sigma-Aldrich
Thrombin from bovine plasma, lyophilized powder, 40-300 NIH units/mg protein (biuret)