Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix
Abstract The efficient establishment of in vitro neural models that accurately mimic the structural and functional connectivity of neural networks is critical in neuroscience research. 3D bioprinting shows great potential for constructing sophisticated in vitro models with high freedom of design. Ho...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202504455 |
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| author | Huiyu Yang Jiangang Zhang Yiran Li Zihan Zhong Wenhua Li Haojun Luo Yanyong Liu Liujian Ouyang Zhuoran Jiang Yuning Sun Hang Sun Lulu Liu Huayu Yang Yu Wang Nan Yang Wenbin Ma Yilei Mao |
| author_facet | Huiyu Yang Jiangang Zhang Yiran Li Zihan Zhong Wenhua Li Haojun Luo Yanyong Liu Liujian Ouyang Zhuoran Jiang Yuning Sun Hang Sun Lulu Liu Huayu Yang Yu Wang Nan Yang Wenbin Ma Yilei Mao |
| author_sort | Huiyu Yang |
| collection | DOAJ |
| description | Abstract The efficient establishment of in vitro neural models that accurately mimic the structural and functional connectivity of neural networks is critical in neuroscience research. 3D bioprinting shows great potential for constructing sophisticated in vitro models with high freedom of design. However, mature neurons are delicate and susceptible to manipulation. Here, extrusion‐based 3D bioprinting is employed to fabricate gelatin methacryloyl (GelMA)‐based constructs containing embryonic day 18 (E18) rat cortical neurons, referred to as 3D neuMatrix. 3D neuMatrix displays favorable neuronal viability, with the progressive formation of a 3D brain‐like neural network with local and long‐range functional axon connections. Compared with 2D cultured neurons, 3D neuMatrix is more similar to the E18 cortex according to the bulk transcriptomic profile, with a recreation of cellular components in the cerebral cortex. The 3D neuMatrix is employed to establish a disease model of ischemic stroke, with a faithful recapitulation of the viability, function, and transcriptomic features of rats with middle cerebral artery occlusion/reperfusion (MCAO/R). These findings demonstrate the formation of multiscale neural circuits within 3D neuMatrix and its valuable potential in the study of neurodevelopment, disease modeling with drug screening, and in vitro intelligence. |
| format | Article |
| id | doaj-art-03dfee55f2bc4c4eafecd3ef0984e2ca |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-03dfee55f2bc4c4eafecd3ef0984e2ca2025-08-20T11:56:10ZengWileyAdvanced Science2198-38442025-08-011230n/an/a10.1002/advs.202504455Multiscale Organization of Neural Networks in a 3D Bioprinted MatrixHuiyu Yang0Jiangang Zhang1Yiran Li2Zihan Zhong3Wenhua Li4Haojun Luo5Yanyong Liu6Liujian Ouyang7Zhuoran Jiang8Yuning Sun9Hang Sun10Lulu Liu11Huayu Yang12Yu Wang13Nan Yang14Wenbin Ma15Yilei Mao16Department of Neurosurgery PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Liver Surgery PUMCH PUMC & CAMS Beijing 100730 ChinaInstitute of Clinical Medicine Translational Medicine Center PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Neurosurgery PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Pharmacology Institute of Basic Medical Sciences CAMS & PUMC Beijing 100005 ChinaDepartment of Pharmacology Institute of Basic Medical Sciences CAMS & PUMC Beijing 100005 ChinaDepartment of Pharmacology Institute of Basic Medical Sciences CAMS & PUMC Beijing 100005 ChinaDepartment of Endocrinology Children's Hospital of Zhejiang University School of Medicine National Clinical Research Center for Child Health Hangzhou Zhejiang 310003 ChinaDepartment of Liver Surgery PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Liver Surgery PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Liver Surgery PUMCH PUMC & CAMS Beijing 100730 ChinaCenter for Biomedical Technology of National Infrastructures for Translational Medicine State Key Laboratory of Complex Severe and Rare Diseases in Peking Union Medical College Hospital Beijing 100730 ChinaDepartment of Liver Surgery PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Neurosurgery PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Pharmacology Institute of Basic Medical Sciences CAMS & PUMC Beijing 100005 ChinaDepartment of Neurosurgery PUMCH PUMC & CAMS Beijing 100730 ChinaDepartment of Liver Surgery PUMCH PUMC & CAMS Beijing 100730 ChinaAbstract The efficient establishment of in vitro neural models that accurately mimic the structural and functional connectivity of neural networks is critical in neuroscience research. 3D bioprinting shows great potential for constructing sophisticated in vitro models with high freedom of design. However, mature neurons are delicate and susceptible to manipulation. Here, extrusion‐based 3D bioprinting is employed to fabricate gelatin methacryloyl (GelMA)‐based constructs containing embryonic day 18 (E18) rat cortical neurons, referred to as 3D neuMatrix. 3D neuMatrix displays favorable neuronal viability, with the progressive formation of a 3D brain‐like neural network with local and long‐range functional axon connections. Compared with 2D cultured neurons, 3D neuMatrix is more similar to the E18 cortex according to the bulk transcriptomic profile, with a recreation of cellular components in the cerebral cortex. The 3D neuMatrix is employed to establish a disease model of ischemic stroke, with a faithful recapitulation of the viability, function, and transcriptomic features of rats with middle cerebral artery occlusion/reperfusion (MCAO/R). These findings demonstrate the formation of multiscale neural circuits within 3D neuMatrix and its valuable potential in the study of neurodevelopment, disease modeling with drug screening, and in vitro intelligence.https://doi.org/10.1002/advs.2025044553D bioprintingCNS diseaseneural networkprimary neuron model |
| spellingShingle | Huiyu Yang Jiangang Zhang Yiran Li Zihan Zhong Wenhua Li Haojun Luo Yanyong Liu Liujian Ouyang Zhuoran Jiang Yuning Sun Hang Sun Lulu Liu Huayu Yang Yu Wang Nan Yang Wenbin Ma Yilei Mao Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix Advanced Science 3D bioprinting CNS disease neural network primary neuron model |
| title | Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix |
| title_full | Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix |
| title_fullStr | Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix |
| title_full_unstemmed | Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix |
| title_short | Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix |
| title_sort | multiscale organization of neural networks in a 3d bioprinted matrix |
| topic | 3D bioprinting CNS disease neural network primary neuron model |
| url | https://doi.org/10.1002/advs.202504455 |
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