4.8 Article

Engineering Human Brain Assembloids by Microfluidics

Journal

ADVANCED MATERIALS
Volume 35, Issue 14, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202210083

Keywords

assembloid-on-a-chip; brain assembloids; brain organoids; microcapsules; microfluidics

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A multidisciplinary engineered strategy based on microfluidic technology is developed to generate human brain assembloids. Using microcapsules and a microfluidic chip, brain organoids can be assembled into desired structures. These brain assembloids exhibit active neural migration and interaction, demonstrating their potential in neurological and biomedical fields.
Brain assembloids offer a highly promising strategy to model human brain development and disease, and advance potential studies in regenerative medicine, therapeutic screening, and drug discovery, while it is challenging to produce uniform brain organoids and assemble them flexibly by conventional methods. Here, a multidisciplinary engineered strategy to generate human brain assembloids with desired patterning based on microfluidic technology is presented. By encapsulating human induced pluripotent stem cells in microcapsules via microfluidic electrospray, brain region-specific organoids are efficiently formed, which are then introduced into a microfluidic chip consisting of a bottom layer with a micropillar array and a movable upper layer with a complementary microhole array. These brain organoids can settle into microholes and fuse into brain assembloids. As varied organoid microcapsules with designed 1D sequences or 2D arrays can be assembled into the vertical microholes, large coding amounts of fused brain assembloids with desired patterning can be produced. It is found that brain assembloids composed of cortical, hippocampal, and thalamic organoids can grow and function well, characterized with active neural migration and interaction. These features indicate that the suggested flexible, scalable, and controlled microfluidic systems are remarkably potential in wide applications of brain assembloids in neurological and biomedical fields.

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