Engineering a 3D human intracranial aneurysm model using liquid-assisted injection molding and tuned hydrogels

Physiologically relevant intracranial aneurysm (IA) models are crucially required to facilitate testing treatment options for IA. Herein, we report the development of a new in vitro tissue-engineered platform, which recapitulates the microenvironment, structure, and cellular complexity of native human IA. A new modified liquid-assisted injection molding technique was developed to fabricate a three-dimensional hollow IA model with clinically relevant IA dimensions within a mechanically tuned Gelatin Methacryloyl (GelMA) hydrogel. An endothelium lining was created inside the IA model by culturing human umbilical vein endothelial cells over pre-cultured human brain vascular smooth muscle cells. These cellularized IA models were subjected to medium perfusion at flow rates between 6.3 and 15.75 mL/min for inducing biomimetic vessel wall shear stress (10-25 dyn/cm(2)) to the cells for ten days. Both cell types maintained their secretome profiles and showed more than 96% viability, demonstrating the biocompatibility of the hydrogel during perfusion cell culture at such flow rates. Based on the characterized viscoelastic properties of the GelMA hydrogel and with the aid of a fluid-structure interaction model, the capability of the IA model in predicting the response of the IA to different fluid flow profiles was mathematically shown. With physiologically relevant behavior, our developed in vitro human IA model could allow researchers to better understand the pathophysiology and treatment of IA. Statement of significance A three-dimensional intracranial aneurysm (IA) tissue model recapitulating the microenvironment, structure, and cellular complexity of native human IA was developed. center dot An endothelium lining was created inside the IA model over pre-cultured human brain vascular smooth muscle cells over at least 10-day successful culture. center dot The cells maintained their secretome profiles, demonstrating the biocompatibility of hydrogel during a long-term perfusion cell culture. center dot The IA model showed its capability in predicting the response of IA to different fluid flow profiles. center dot The cells in the vessel region behaved differently from cells in the aneurysm region due to alteration in hemodynamic shear stress. center dot The IA model could allow researchers to better understand the pathophysiology and treatment options of IA. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

Physiologically relevant intracranial aneurysm (IA) models are crucial for testing treatment options for IA. In this study, a new in vitro tissue-engineered platform was developed to mimic the microenvironment, structure, and cellular complexity of native human IA. The cellularized IA models demonstrated high viability and maintained their secretome profiles during medium perfusion, showing the biocompatibility of the hydrogel. The IA models showed the ability to predict the response of IA to different fluid flow profiles, providing insights into the pathophysiology and treatment options for IA.