Zhu Yujuan, Zhang Xiaoxuan, Sun Lingyu, Wang Yu, Zhao Yuanjin
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001, China.
Adv Mater. 2023 Apr;35(14):e2210083. doi: 10.1002/adma.202210083. Epub 2023 Mar 2.
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.
脑类器官聚集体为模拟人类大脑发育和疾病以及推进再生医学、治疗筛选和药物发现等潜在研究提供了一种极具前景的策略，然而，采用传统方法生产均匀的脑类器官并灵活组装它们具有挑战性。在此，我们提出了一种基于微流控技术生成具有所需图案的人类脑类器官聚集体的多学科工程策略。通过微流控电喷雾将人类诱导多能干细胞封装在微胶囊中，可高效形成脑区特异性类器官，然后将其引入由带有微柱阵列的底层和带有互补微孔阵列的可移动上层组成的微流控芯片中。这些脑类器官可落入微孔并融合成脑类器官聚集体。由于具有设计好的一维序列或二维阵列的各种类器官微胶囊可组装到垂直微孔中，因此可以生产出大量具有所需图案的融合脑类器官聚集体。研究发现，由皮质、海马和丘脑类器官组成的脑类器官聚集体能够良好生长并发挥功能，其特征为活跃的神经迁移和相互作用。这些特性表明，所提出的灵活、可扩展且可控的微流控系统在脑类器官聚集体在神经学和生物医学领域的广泛应用中具有巨大潜力。
