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A novel method for generating 3D constructs with branched vascular networks using multi-materials bioprinting and direct surgical anastomosis

Xin Liu, Xinhuan Wang, Liming Zhang, Lulu Sun, Heran Wang, Hao Zhao, Zhengtao Zhang, Yiming Huang, Jingjinqiu Zhang, Biaobiao Song, Chun Li, Hui Zhang, Song Li, Shu Wang, Xiongfei Zheng, View ORCID ProfileQi Gu
doi: https://doi.org/10.1101/2021.03.21.436268
Xin Liu
2Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
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Xinhuan Wang
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China, E-mails:
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  • For correspondence: qgu@ioz.ac.cn
Liming Zhang
3Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110169, P. R. China E-mails:
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  • For correspondence: zhengxiongfei@sia.cn
Lulu Sun
5State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, P. R. China
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Heran Wang
3Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110169, P. R. China E-mails:
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  • For correspondence: zhengxiongfei@sia.cn
Hao Zhao
4Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 P. R. China E-mails:
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  • For correspondence: wangshu@iccas.ac.cn
Zhengtao Zhang
5State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, P. R. China
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Yiming Huang
4Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 P. R. China E-mails:
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  • For correspondence: wangshu@iccas.ac.cn
Jingjinqiu Zhang
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China, E-mails:
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  • For correspondence: qgu@ioz.ac.cn
Biaobiao Song
6University of Science and Technology of China, Hefei, 230026, P. R. China
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Chun Li
5State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, P. R. China
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Hui Zhang
3Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110169, P. R. China E-mails:
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  • For correspondence: zhengxiongfei@sia.cn
Song Li
3Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110169, P. R. China E-mails:
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  • For correspondence: zhengxiongfei@sia.cn
Shu Wang
4Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 P. R. China E-mails:
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  • For correspondence: wangshu@iccas.ac.cn
Xiongfei Zheng
3Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110169, P. R. China E-mails:
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  • For correspondence: zhengxiongfei@sia.cn
Qi Gu
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China, E-mails:
2Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
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  • ORCID record for Qi Gu
  • For correspondence: qgu@ioz.ac.cn qgu@ioz.ac.cn
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Abstract

Vessels pervade almost all body tissues, and significantly influence the pathophysiology of human body. Previous attempts to establish multi-scale vascular connection and function in 3D model tissues using bioprinting have had limited success due to the incoordination between cell-laden materials and stability of the perfusion channel. Here, we report a methodology to fabricate centimetre-scale vascularized soft tissue with high viability and accuracy using multi-materials bioprinting involving inks with low viscosity and a customized multistage-temperature-control printer. The tissue formed was perfused with branched vasculature with well-formed 3D capillary network and lumen, which would potentially supply the cellular components with sufficient nutrients in the matrix. Furthermore, the same methodology was applied for generating liver-like tissue with the objective to fabricate and mimic a mature and functional liver tissue, with increased functionality in terms of synthesis of liver specific proteins after in vitro perfusion and in vivo subperitoneal transplantation in mice. Moreover, to establish immediate blood perfusion, an elastic layer was printed wrapping sacrificial ink to support the direct surgical anastomosis of the carotid artery to the jugular vein. Our findings highlight the support extended by vasculature network in soft hydrogels which helps to sustain the thick and dense cellularization in engineered tissues.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted March 22, 2021.
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A novel method for generating 3D constructs with branched vascular networks using multi-materials bioprinting and direct surgical anastomosis
Xin Liu, Xinhuan Wang, Liming Zhang, Lulu Sun, Heran Wang, Hao Zhao, Zhengtao Zhang, Yiming Huang, Jingjinqiu Zhang, Biaobiao Song, Chun Li, Hui Zhang, Song Li, Shu Wang, Xiongfei Zheng, Qi Gu
bioRxiv 2021.03.21.436268; doi: https://doi.org/10.1101/2021.03.21.436268
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A novel method for generating 3D constructs with branched vascular networks using multi-materials bioprinting and direct surgical anastomosis
Xin Liu, Xinhuan Wang, Liming Zhang, Lulu Sun, Heran Wang, Hao Zhao, Zhengtao Zhang, Yiming Huang, Jingjinqiu Zhang, Biaobiao Song, Chun Li, Hui Zhang, Song Li, Shu Wang, Xiongfei Zheng, Qi Gu
bioRxiv 2021.03.21.436268; doi: https://doi.org/10.1101/2021.03.21.436268

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