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International Journal of Bioprinting


                                        RESEARCH ARTICLE
                                        Biomimetic three-dimensional glioma model

                                        printed in vitro for the studies of glioma cells and
                                        neurons interactions



                                        Luge Bai , Zhiyan Hao , Sen Wang , Jiajia Zhou , Siqi Yao , Na Pei ,
                                                                       1,2
                                                                                  1,2
                                               1,2
                                                            1,2
                                                                                            1,2
                                                                                                    1,2
                                        Hui Zhu , Kun Zhang , Rui L. Reis , J. Miguel Oliveira , Jiankang He ,
                                               1,2
                                                           3
                                                                                                   1,2
                                                                                      4,5
                                                                     4,5
                                        Dichen Li , Xinggang Mao *, Ling Wang *
                                                               6
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                                                1,2
                                        1 School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an 710054, Shaanxi, China
                                        2 NMPA Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices,
                                        Xi’an Jiaotong University, Xi’an 710054, Shaanxi, China
                                        3 Department  of  Pharmacology,  School  of  Pharmacy,  Fourth  Military  Medical  University,  Xi’an,
                                        Shaanxi, China
                                        4 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables and Biomimetics,
                                        University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering
                                        and Regenerative Medicine, AvePark, Zona Industrial da Gandra, 4805-017 Barco -Guimarães,
                                        Portugal
                                        5
                                        ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal
                                        6 Department of Neurosurgery, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shaanxi,
                                        China
                                        (This article belongs to the Special Issue: Advances in 3D bioprinting based on lab-on-a-chip platforms for
                                        precision oncology)
            *Corresponding authors:
            Ling Wang                   Abstract
            (menlwang@xjtu.edu.cn)
            Xinggang Mao                The interactions between glioma cells and neurons are important for glioma
            (xgmao@fmmu.edu.cn)         progression but are rarely mimicked and recapitulated in in vitro three-dimensional
            Citation: Bai L, Hao Z, Wang S,   (3D) models, which may affect the success rate of relevant drug research and
            et al., 2023, Biomimetic three-  development.  In  this  study,  an  in vitro bioprinted  3D  glioma  model  consisting  of
            dimensional glioma model printed    an outer hemispherical shell with neurons and an inner hemisphere with glioma
            in vitro for the studies of glioma
            cells and neurons interactions.     cells is proposed to simulate the natural glioma.  This model was produced by
             Int J Bioprint, 9(4): 715.  extrusion-based 3D bioprinting technology. The cells survival rate, morphology, and
            https://doi.org/10.18063/ijb.715  intercellular Ca  concentration studies were carried out up to 5 days of culturing.
                                                    2+
            Received: November 25, 2022  It was found that neurons could promote the proliferation of glioma cells around
            Accepted: January 10, 2023  them, associate the morphological changes of glioma cells to be neuron-like, and
            Published Online: March 21, 2023
                                        increase the expression of intracellular Ca  of glioma cells. Conversely, the presence
                                                                          2+
            Copyright: © 2023 Author(s).   of glioma cells could maintain the neuronal survival rate and promote the neurite
            This is an Open Access article   outgrowth. The results indicated that glioma cells and neurons facilitated each other
            distributed under the terms of the
            Creative Commons Attribution   implying a symbiotic pattern established between two types of cells during the early
            License, permitting distribution   stage of glioma development, which were seldom found in the present artificial
            and reproduction in any medium,   glioma models.  The proposed bioprinted glioma model can mimic the natural
            provided the original work is
            properly cited.             microenvironment of glioma tissue, provide an in-depth understanding of cell–cell
                                        interactions, and enable pathological and pharmacological studies of glioma.
            Publisher’s Note: Whioce
            Publishing remains neutral with
            regard to jurisdictional claims in
            published maps and institutional   Keywords: In vitro 3D model; Glioma model; 3D bioprinting; Glioma cells; Neurons
            affiliations.



            Volume 9 Issue 4 (2023)                         1                           https://doi.org/10.18063/ijb.715
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