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     REVIEW ARTICLE
           Bio-assembling and Bioprinting for Engineering
           Microvessels from the Bottom Up
           Xiaoming Liu *, Tao Yue , Masaru Kojima , Qiang Huang *, Tatsuo Arai      1,5
                         1
                                    2,3
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           1 Key Laboratory of Biomimetic Robots and Systems, Ministry of Education, State Key Laboratory of Intelligent Control
           and Decision of Complex System, Beijing Advanced Innovation Center for Intelligent Robots and Systems, and School of
           Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China
           2 School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China
           3 Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai 200092, China
           4 Department of Materials Engineering Science, Osaka University, Osaka 5608531, Japan
           5 Center for Neuroscience and Biomedical Engineering, the University of Electro-Communications, Tokyo 1828585, Japan.
           Abstract: Blood vessels are essential in transporting nutrients, oxygen, metabolic wastes, and maintaining the homeostasis of
           the whole human body. Mass of engineered microvessels is required to deliver nutrients to the cells included in the constructed
           large three-dimensional (3D) functional tissues by diffusion. It is a formidable challenge to regenerate microvessels and build
           a microvascular network, mimicking the cellular viabilities and activities in the engineered organs with traditional or existing
           manufacturing techniques. Modular tissue engineering adopting the “bottom-up” approach builds one-dimensional (1D) or
           two-dimensional (2D) modular tissues in micro scale first and then uses these modules as building blocks to generate large
           tissues and organs with complex but indispensable microstructural features. Building the microvascular network utilizing this
           approach could be appropriate and adequate. In this review, we introduced existing methods using the “bottom-up” concept
           developed  to  fabricate  microvessels  including  bio-assembling  powered  by  different  micromanipulation  techniques  and
           bioprinting utilizing varied solidification mechanisms. We compared and discussed the features of the artificial microvessels
           engineered by these two strategies from multiple aspects. Regarding the future development of engineering the microvessels
           from the bottom up, potential directions were also concluded.
           Keywords: Microvessels; Bio-assembling; Bioprinting; Bottom-up; Tissue engineering
           *Correspondence to: Xiaoming Liu, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China; liuxiaoming555@
           bit.edu.cn; Qinag Huang, School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081;qhuang@bit.edu.cn
           Received: April 7, 2021; Accepted: May 7, 2021; Published Online: June 11, 2021
           (This article belongs to the Special Section: Bioprinting of 3D Functional Tissue Constructs)
           Citation: Liu, X, Yue, T, Kojima, M, et al., 2021, Bioassembling and Bioprinting for Engineering Microvessels from the
           Bottom Up. Int J Bioprint. 7(3):366. http://doi.org/10.18063/ijb.v7i3.366
           1. Introduction                                     molecules,  and organic  materials . In the  past  two
                                                                                            [4]
                                                               decades,  significant  advances  have  been  achieved  in
           Tissues such as bone and skin have the ability to repair   tissue engineering. Many different kinds of tissues have
           slight injuries by themselves [1-3] . However, many serious
           tissue injuries and multiple  organ failures can hardly   been fabricated,  but most of these engineered  tissues
                                                                                                  [9,10]
           be  effectively  cured  by  conventional  interventional,   feature thin slices and simple architectures  . The main
           pharmacological,  and  surgical  therapies,  except  organ   reason is the challenges in including the microvascular
                                                                                                          [11]
           transplantation [4-6] .  Unfortunately,  organ  transplantation   networks in the large functional regenerated tissues .
           in the clinic is greatly limited by the shortage of     Blood  vessels are  essential  in  transporting
           donors [7,8] . Tissue engineering was introduced by Langer   nutrients, oxygen, metabolic wastes, and maintaining the
           30  years  before  targeting  to  build  artificial  functional   homeostasis of the whole human body. Mass of engineered
           tissue substitutes through combining specific cell lines,   microvessels is required to deliver nutrients to the cells
           © 2021 Liu, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons. org/
           licenses/by/4.0/), permitting distribution and reproduction in any medium, provided the original work is cited.
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