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The microfluidic chip was designed with a micropillar array for the controlled and efficient generation of cortical organoids. With low oxygen, the generated cortical organoids could recapitulate key aspects of early-gestational human brain development. Compared to organoids in normoxic culturing condition, the promoted neurogenesis, synaptogenesis and neuronal maturation were observed in the present microsystem, suggesting the significance of physiological hypoxia in cortical development. Based on this model, we have found that Chinese herbal drug Tan IIA could promote neural differentiation and maturation, indicating its potential therapeutic effects on neurodevelopmental disorders as well as congenital neuropsychiatric diseases. These results indicate that the proposed biomimetic cortical organoid-on-a-chip model with physiological hypoxia can offer a promising platform to simulate prenatal environment, explore brain development, and screen natural neuroactive components.<\/jats:p>","DOI":"10.34133\/research.0273","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T16:26:56Z","timestamp":1699892816000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":23,"title":["Cortical Organoid-on-a-Chip with Physiological Hypoxia for Investigating Tanshinone IIA-Induced Neural Differentiation"],"prefix":"10.34133","volume":"6","author":[{"given":"Yue","family":"Zhi","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, \rNanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, \rSoutheast University, Nanjing, 210096, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, \rSoutheast University, Nanjing, 210096, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, \rSoutheast University, Nanjing, 210096, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, \rNanjing Drum Tower Hospital, Clinical Medical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China."},{"name":"State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, \rSoutheast University, Nanjing, 210096, China."},{"name":"Shenzhen Research Institute, \rSoutheast University, Shenzhen, 518038, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012927"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba4517"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04358-6"},{"issue":"32","key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"e2210631","DOI":"10.1002\/adma.202210631","article-title":"Rationally design and acoustically assemble human cerebral cortex-like microtissues from hiPSC-derived neural progenitors and neurons","volume":"35","author":"Wang J","year":"2023","unstructured":"Wang J, Qiao H, Wang Z, Zhao W, Chen T, Li B, Zhu L, Chen S, Gu L, Wu Y, et al. 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