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RESEARCH ARTICLE

           Coaxial Electrohydrodynamic Bioprinting of

           Pre-vascularized Cell-laden Constructs for Tissue

           Engineering


           Mao Mao , Hongtao Liang , Jiankang He *, Ayiguli Kasimu , Yanning Zhang , Ling Wang ,
                                                                                                          1,2
                                                                                            1,2
                                                                          1,2
                    1,2
                                                      1,2
                                      1,2
           Xiao Li , Dichen Li 1,2
                  1,2
           1 State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an 710049, China
           2 NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices, Xi’an Jiaotong
           University, Xi’an 710049, China
           Abstract: Recapitulating the vascular networks that maintain the delivery of nutrition, oxygen, and byproducts for the living
           cells within the three-dimensional (3D) tissue constructs is a challenging issue in the tissue-engineering area. Here, a novel
           coaxial electrohydrodynamic (EHD) bioprinting strategy is presented to fabricate thick pre-vascularized cell-laden constructs.
           The alginate and collagen/calcium chloride solution were utilized as the outer-layer and inner-layer bioink, respectively, in
           the coaxial printing nozzle to produce the core-sheath hydrogel filaments. The effect of process parameters (the feeding rate
           of alginate and collagen and the moving speed of the printing stage) on the size of core and sheath lines within the printed
           filaments was investigated. The core-sheath filaments were printed in the predefined pattern to fabricate lattice hydrogel
           with perfusable lumen structures. Endothelialized lumen structures were fabricated by culturing the core-sheath filaments
           with endothelial cells laden in the core collagen hydrogel. Multilayer core-sheath filaments were successfully printed into
           3D porous hydrogel constructs with a thickness of more than 3 mm. Finally, 3D pre-vascularized cardiac constructs were
           successfully generated, indicating the efficacy of our strategy to engineer living tissues with complex vascular structures.
           Keywords: Electrohydrodynamic bioprinting; Coaxial bioprinting; Vascularized tissues; Biofabrication; Core-sheath filaments


           *Correspondence to: Jiankang He, State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an 710049,
           China; jiankanghe@mail.xjtu.edu.cn

           Received: April 3, 2021; Accepted: May 14, 2021; Published Online: June 4, 2021
           (This article belongs to the Special Section: Bioprinting of 3D Functional Tissue Constructs)
           Citation: Mao M, Liang H, He J, et al., 2021, Coaxial Electrohydrodynamic Bioprinting of Pre-vascularized Cell-laden
           Constructs for Tissue Engineering. Int J Bioprint, 7(3):362. http://doi.org/10.18063/ijb.v7i3.362


           1. Introduction                                     endothelial cells in the spatially predefined organization,
                                                               with an attempt to build microvessels within the cell-
           One of the most challenging problems in the tissue   laden  constructs [4-8] .  It  has  been  demonstrated  that  the
           engineering  area  is to fabricate functional  vasculature   endothelial cells in the spatially predefined organization
           within the three-dimensional (3D) engineered  tissue   can  significantly  improve  the  speed  and  extent  of  the
           that  provides  enough nutrition and  oxygen  to  the  cells   vascularization  after  implantation,  compared  to that  in
           and  transports the  byproducts . Cellular  viability   a random distribution [9,10] . However, these engineering
                                       [1]
           and function  will  be compromised, and necrosis may   methods could only be used to fabricate constructs with
           further occur without a capillary network within a few   relatively  simple  architectures  and homogeneous cell-
           hundred microns of cells [2,3] .  Thus, many approaches   laden matrices, which make them difficult to recapitulate
           such as microreplication,  photolithography, and    the intricate  3D structure  and composition  of natural
           sacrificial molding have been proposed to organize the   tissues [11,12] .

           © 2021 Mao, 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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