Bioengineering tools for next-generation neural organoids

Abstract

Human stem cell–derived neural organoids were recently introduced as powerful in vitro 3D experimental model systems that innately undergo critical steps of organogenesis in culture and exhibit molecular, cellular, and structural features similar to the fetal human nervous system. These organoids have yielded new insights into human neurodevelopment and associated disorders. However, neural organoids have some crucial limitations that arise from the loosely controlled conditions for their development, an inability to maintain their spatial orientation in culture and a lack of technologies for taking long-term measurements on their morphology and electrical activity. Here, we review recent progress in using bioengineering methods to improve neural organoid formation and analysis by leveraging microfabrication, biomaterials, 3D printing, and flexible electrodes. We discuss how the applications of each technique can help to address critical limitations with standard neural organoid models. We conclude with a perspective on future applications of bioengineered next-generation neural organoids.