Microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

TLDR

Brain organoids derived from human pluripotent stem cells are valuable in vitro models, yet current culture systems lack reliability and high quality. The study aims to improve brain organoid culture by incorporating a brain extracellular matrix and a microfluidic device with periodic flow. The authors use a brain‑specific extracellular matrix to provide cues and a microfluidic chamber that delivers periodic flow to enhance survival and reduce variability. These engineering elements significantly boost neurogenesis, cortical layer formation, organoid volume, and electrophysiological function, establishing a reproducible platform for disease modeling and drug development.

Abstract

Abstract Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with brain extracellular matrix significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.