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International Journal of Bioprinting                                3D bioprinting technology for brain tumor




            Table 1. Bioinks and printed TME components in brain tumors
             Component                      Bioink       Method    Properties of 3D-printed  Experimental   Reference
                                                                   model                   design
             Glioma cell   -                GAF,        Extrusion  Expresses stability,   In vitro and  29,30
             (U118)                      transglutaminase          upregulated EMT, stemness,   in vivo
                                                                   chemoresistance, and
                                                                   tumorigenicity
                        GSC (GSC23)        SA, gelatin  Extrusion  Exhibits proliferation and   In vitro and  31,32
                                                                   angiogenesis            in vivo
                        GSC (GSC23)          SA         Extrusion  Higher drug resistance  In vitro     33,34
             Glioblastoma   GSC (SU3)       GAF         Extrusion  Enhanced drug resistance   In vitro  35,36
             cell (U87)                                            and cell viability
                        HUVECs, LFs         GAF           N/A      Distinct angiogenesis and   In vitro  37–38
                                                                   EMT
                        GFP-expressing U87,   MRCSs       TPL      Constructs the complex   In vitro     40
                        hCMEC/D3                                   BBB system
                        Patient-derived    BdECM or   GBM-on-a-chip  Incorporates heterogeneous   In vitro  39,41
                        GBM, HUVECs        collagen                TME; demonstrates patient-
                                                                   specific therapy resistance
                        -                  Matrigel      MEW       Facilitates cell growth,   In vitro  42,43
                                                                   migration, and drug
                                                                   screening
                        Astrocytes        Fibrinogen,   Extrusion  Feasible to test cell viability   In vitro  4,44,45
                                         alginate,genipin          against drug
             GSC (GSC23)  -                 GAF         Extrusion  Alters cell morphology;   In vitro   46,47
                                                                   promotes vasculogenesis
                                                                   and stemness
                        MSCs                GAF         Extrusion  High cell viability; sufficient   In vitro  47
                                                                   cell–cell interaction
                        Macrophages,     GMHA, GelMA      DLP      Upregulated GBM tissue-  In vitro and  9,2
                        astrocytes, NPCs                           specific genes; activates   in vivo
                                                                   ECM and invasiveness
                        GASCs, microglia  HA, RGD-alginate  Extrusion  Higher drug sensitivity   In vitro  48,49
                                                                   in TMZ and cisplatin;
                                                                   maintains pluripotency

            Abbreviations: BBB, blood–brain barrier; BdECM, brain decellularized extracellular matrix; DLP, digital light processing; ECM, extracellular matrix;
            EMT, epithelial-mesenchymal transition; GAF, gelatin, alginate, fibrinogen; GASCs, glioma associated stromal cells; GBM, glioblastoma; GelMA, gelatin
            methacrylate; GFP, green fluorescent protein; GMHA: glycidyl methacrylate-hyaluronic acid; GSC, glioblastoma stem cell; HA, hyaluronic acid; hCMEC/
            D3, human cerebral microvascular endothelial cell line; HUVECs, human vascular endothelial cells; LFs, lung fibroblasts; MEW, melt electrowriting;
            MRCSs, magnetically responsive cage-like scaffolds; MSCs, mesenchymal stem cells; NPCs, neural precursor cells; RGD-alginate, alginate modified by
            Arg-Gly-Asp peptide sequence; SA, sodium alginate; TME, tumor microenvironment; TMZ, temozolomide; TPL, two-photon lithography.

            the rapid printing speed is a significant advantage.    3. Mimicking the brain TME using
                                                         23
            Similarly, laser-assisted printing can dispense formulated   3D bioprinting
            cells drop-by-drop using a pulsed laser.  It is highly
                                              51
            efficient compared to other methods because nozzles are   The brain TME plays a pivotal role in tumor progression,
                                                               metabolism, and metastasis. Optimized  physiological
            unnecessary; therefore, it can deliver a higher viscosity and   conditions for tumor development are formed by
            density of cells with better viability.  DLP and two-photon   communication between various cell types, including
                                        23
            polymerization-based bioprinting are light-assisted   GSCs, glioma cells, microglia, astrocytes, neurons,
            bioprinting techniques that can be used for sensitive cell   mesenchymal  stem  cells,  and  tumor-associated
            types.  Overall, selecting the right bioprinting method and   microglia.  Tumor-associated microglia with an M2
                24
                                                                       24
            bioink has a critical impact on establishing an appropriate   pro-tumor phenotype create an immunosuppressive
            3D model for brain tumor modeling.                 TME and promote tumor growth.57 When extracellular

            Volume 10 Issue 6 (2024)                       157                                doi: 10.36922/ijb.4166
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