Development of 3D functional brain tissue model

Nervous system disorders including acute traumatic injuries, neurodegenerative diseases, and neurodevelopmental disorders are estimated to affect more than one billion people worldwide. Study and understanding the development of the human nervous system and exposing the mechanisms of mental disorders has greatly been limited due to the restricted access to the functional human brain tissue. 3D in vitro organ models has recently shown to be a powerful tool for biological and medical studies. These models, however, require special 3D construction of cell and extracellular matrixes that are often hard to achieve with conventional fabrication approaches. Bioprinting technique has emerged as potent platform to fabricate these complex 3D models. Here, state-of-art stem cell-based 3D in vitro brain models that recapitulate the geometrical complexity of the brain are developed using 3D bioprinting. The model is developed based on two cell types, neural stem cell and primary astrocytes. To create the model, a high-throughput biofabrication strategy based on embedded 3D bioprinting technology is designed, developed and characterized. Protocols, culture media, bioinks and biomaterials used are tuned and optimized to increase cell viability, enhance cell activity and promote neural stem cell differentiation. The procedures are optimized through a series of 2D and 3D studies and finally, the 3D bioprinted brain in vitro model is carried out. Keywords: Brain tissue, Neural stem cells, Bioprinting, DifferentiationApplied Science, Faculty ofMechanical Engineering, Department ofGraduat