biostudies-literatureWang YChinese Academy of SciencesNational Natural Science Foundation of China1677-1685https://www.ebi.ac.uk/biostudies/studies/S-EPMC9077091biostudies-literatureUnknown8(3)Brain organoids derived from the self-organization of human induced pluripotent stem cells (hiPSCs) represent a new class of <i>in vitro</i> organ system for modeling brain development and diseases. However, engineering brain organoids in a biomimetic environment that is favorable for brain development remains challenging. In this work, we present a new strategy to generate hiPSCs-derived 3D brain organoids using an organ-on-a-chip system in a controlled manner. This system provides a biomimetic brain microenvironment by incorporating three-dimensional (3D) Matrigel, fluid flow and multicellular architectures of tissues that allows for extended 3D culture, <i>in situ</i> neural differentiation, and organization of brain organoids on a single device. The generated brain organoids display weRSC advancesEngineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system.PMC9077091316710383160078481573394XDA1602090091543121XDPB0305Guo YZhu YQin JWang YWang LfalseEngineering stem cell-derived 3D brain organoids in a perfusable organ-on-a-chip system.Brain organoids derived from the self-organization of human induced pluripotent stem cells (hiPSCs) represent a new class of <i>in vitro</i> organ system for modeling brain development and diseases. However, engineering brain organoids in a biomimetic environment that is favorable for brain development remains challenging. In this work, we present a new strategy to generate hiPSCs-derived 3D brain organoids using an organ-on-a-chip system in a controlled manner. This system provides a biomimetic brain microenvironment by incorporating three-dimensional (3D) Matrigel, fluid flow and multicellular architectures of tissues that allows for extended 3D culture, <i>in situ</i> neural differentiation, and organization of brain organoids on a single device. The generated brain organoids display we2018-01-01T00:00:00Z2018 Jan2025-04-04T20:50:49.75Z2025-02-19T03:24:57.996ZS-EPMC90770913554086710.1039/c7ra11714k