Multiscale Organization of Neural Networks in a 3D Bioprinted Matrix.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published Date:

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.

Authors

  • Huiyu Yang
    Department of Neurosurgery, PUMCH, PUMC & CAMS, Beijing, 100730, China.
  • Jiangang Zhang
    Department of Liver Surgery, PUMCH, PUMC & CAMS, Beijing, 100730, China.
  • Yiran Li
    University of California at Davis, Davis, CA, USA.
  • Zihan Zhong
    Department of Neurosurgery, PUMCH, PUMC & CAMS, Beijing, 100730, China.
  • Wenhua Li
    Ultrasound in Cardiac Electrophysiology and Biomechanics Key Laboratory of Sichuan Province, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, 32# W. Sec 2, 1st Ring Rd., Chengdu, 610072, China.
  • Haojun Luo
    Department of Pharmacology, Institute of Basic Medical Sciences, CAMS & PUMC, Beijing, 100005, China.
  • Yanyong Liu
    Department of Pharmacology, Institute of Basic Medical Sciences, CAMS & PUMC, Beijing, 100005, China.
  • Liujian Ouyang
    Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310003, China.
  • Zhuoran Jiang
  • Yuning Sun
    Department of Liver Surgery, PUMCH, PUMC & CAMS, Beijing, 100730, China.
  • Hang Sun
    CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
  • Lulu Liu
    Analytical Center, Neurology Department of Affiliated Hospital, Institute of Neurology, Guangdong Medical University, Zhanjiang, Guangdong 524023, China. caichun2006@tom.com chenyusen925@163.com.
  • Huayu Yang
    Department of Liver Surgery, PUMCH, PUMC & CAMS, Beijing, 100730, China.
  • Yu Wang
    Clinical and Technical Support, Philips Healthcare, Shanghai, China.
  • Nan Yang
    Department of Infectious Disease, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: Shmily.1989.2008@stu.xjtu.edu.cn.
  • Wenbin Ma
    Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan Hutong, Dongcheng District, Beijing, 100730, China. Wbin718@126.com.
  • Yilei Mao
    Department of Liver Surgery, Peking Union Medical College Hospital, Dongcheng-qu, China pumch-liver@hotmail.com.

Keywords

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