Recent Advances in Brain Organoid Technology for Human Brain Research

Brain organoids are self-assembled three-dimensional aggregates with brain-like cell types and structures and have emerged as new model systems that can be used to investigate human neurodevelopment and neurological disorders. However, brain organoids are not as mature and functional as real human brains due to limitations of the culture system with insufficient developmental patterning signals and a lack of components that are important for brain development and function, such as the non-neural population and vasculature. In addition, establishing the desired brain-like environment and monitoring the complex neural networks and physiological functions of the brain organoids remain challenging. The current protocols to generate brain organoids also have problems with heterogeneity and batch variation due to spontaneous self-organization of brain organoids into complex architectures of the brain. To address these limitations of current brain organoid technologies, various engineering platforms, such as extracellular matrices, fluidic devices, three-dimensional bioprinting, bioreactors, polymeric scaffolds, microelectrodes, and biochemical sensors, have been employed to improve neuronal development and maturation, reduce structural heterogeneity, and facilitate functional analysis and monitoring. In this review, we provide an overview of the latest engineering techniques that overcome these limitations in the production and application of brain organoids.