Two-step method fabricating a 3D nerve cell model with brain-like mechanical properties and tunable porosity vascular structures via coaxial printing

Three-dimensional (3D) nerve cell models have been widely developed to understand the mechanisms and discover treatment methods of ischemic stroke and neurodegenerative disease. However, there is a contradiction in the production of 3D models that they should possess high modulus to ensure mechanical stability while low modulus to provide mechanical stimuli for nerve cells. In addition, it is challenging to maintain the long-term viability of 3D models when lacking vascular structures. Here, a 3D nerve cell model with brain-like mechani-cal properties and tunable porosity vascular structures has been fabricated. The matrix materials with brain-like low mechanical properties were favorable for promoting HT22 proliferation. The nerve cells could exchange nutrients and waste with the cultural environment through vascular structures. The vascular structures also played a supporting role, and model stability was enhanced by combining matrix materials with vascular structures. Furthermore, the porosity of vascular structure walls was adjusted by adding sacrificial materials to the tube walls during 3D coaxial printing and removing them after preparation, resulting in tunable porosity vascular structures. Finally, HT22 cells showed better cell viability and proliferation performance after culturing 7 days in the 3D models with vascular structures than in the 3D models with solid structures. All these results suggest that this 3D nerve cell model possesses good mechanical stability and long-term viability, which is ex-pected to be used in pathological studies and drug screening for ischemic stroke and neurodegenerative diseases.