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International Journal of Bioprinting 3D bioprinting technology for brain tumor

3D-bioprinted scaffolds have also been used in tumor fabrication systems for organ-on-a-chip have limitations
vascularization research. The 3D-bioprinted tumor in creating tissue structures with a complicated 3D
model, mimicking the in vivo TME, has contributed to organization. The integration of 3D bioprinting with
the search for 3D-bioprinted glioma stem cells in tumor a chip has a synergistic effect on transforming in vitro
angiogenesis. A hydrogel scaffold containing glioma models by incorporating physiological compositions into
stem cells (GSC23) was constructed using a bioprinter. a controlled extracellular environment. For example,
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Traditional 2D suspension-cultured cells proliferated 3D-bioprinted vessels-on-chips are superior to cell-seeded
dramatically but decreased after 5 days. Meanwhile, structures and can be manipulated mechanically to evoke
3D-bioprinted scaffold cells grew steadily over 10 days a physiological response. 56
and consistently increased the secretion of VEGFA, a Microfluidic organ-on-a-chip models control the
major stimulator of tumor angiogenesis, after 9 days. 83,84 organ microenvironment using living cells to simulate
QThe mRNA levels of CD31, VEGFR2, HIF-1α, and organ-level functions in vitro, including the lungs, liver,
CD133, i.e., endothelial-specific makers of growth, kidneys, and heart. Moreover, a mini-brain tumor-on-
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metastasis, and angiogenesis, are higher in 3D-cultured a-chip was developed to mimic the in vivo TME. These
cells than in the suspension culture. Regarding the chips are useful tools for brain tumor research because
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stemness of GSC23, the proportion of CD133+ cells in they recapitulate the essential properties of a complicated
3D-bioprinted scaffolds was remarkably higher than that neural environment. The GBM-on-a-chip models are
in the 2D suspension culture. commonly based on microfluidic technology. The major
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The 3D monoculture GBM model mimics the polymeric material used to manufacture microfluidic chips
angiogenic process of GBM and has been used to study is polydimethylsiloxane, which has advantages such as
antiangiogenic therapy with bevacizumab. Although transparency, biocompatibility, flexibility, and resolution.
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antiangiogenic therapy delays the recurrence of GBM, Although in vivo analyses are widely conducted to study
the effects are transient due to drug resistance in many brain tumors, several crucial factors diminish precision and
patients. In general, a 3D GBM model for GBM reproducibility, such as species differences in physiological
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research is structured as a monoculture of GBM cell lines, mechanisms. The integration of 3D bioprinting and on-
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including U118 (a human glioma cell line) or GSC23 cells a-chip microfluidic platforms facilitates rapid assessment
(a human glioma stem cell line). To closely mimic the of the effects of mechanical forces, drug components,
neovascularization of GBM, both cell types formed a GBM and drug concentrations on cell growth and development
cell morphology during monoculture encapsulated in a through dynamic stress loading, growth factors, and
gelatin-alginate-fibrinogen hydrogel using a multi-nozzle drug stimulation. 41
extrusion-based bioprinter. 3D-GSC23 and 3D-U118
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cells exhibit neovascularization ability and secrete VEGFA 5.1. BBB-on-a-chip model
proteins that promote angiogenesis and induce vascular The BBB-on-a-chip model (BBBoC) system is an
permeability. 87,88 Moreover, tubule-like structures are important device for developing high-quality BBB models
formed by 3D-GSC23, indicating their ability to promote (Figure 3). The BBBoC is based on a microfluidic platform
neovascularization by transdifferentiating into endothelial composed of three layers: lid, chamber, and perfusion
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cells. Xenograft models derived from 3D-GSC23 and 3D- layers. BMECs and astrocytes were co-cultured between
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U118 cells displayed abundant blood vessels on the surface the chamber and perfusion layers; this structure included
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of tumors and secreted VEGFA in vitro. 87 silicon sheets and porous membranes. This device uses
BMECs derived from human-induced pluripotent stem
5. Tumor-on-a-chip model with 3D bioprinting cells to achieve barrier tightness. Fluorescent images
3D bioprinting technology has also been utilized for the from immunostaining displayed high-level tight junction
development of tumor-on-a-chip. Organs-on-a-chip proteins (claudin-5 and ZO-1), 99,100 suggesting that
is a well-established microfluidics-based technology barrier integrity was well-established and maintained in
that offers features that closely mimic the mechanical microfluidic BBBoCs based on induced pluripotent stem
and/or chemical in vivo conditions of vasculature-like cells. 98,101 BBB permeability was assessed using three small-
structures. 89,90 By using organ-on-a-chip, the functional molecule drugs: caffeine, cimetidine, and doxorubicin.
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units of human tissues and organs can be reconstructed The chip exhibited differential permeability to the
ex vivo on microscopic cell and tissue culture platforms. aforementioned molecules, similar to in vivo conditions.
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These platforms incorporate essential components such The ability to closely reproduce permeability similar to
as multicellular structures, ECM, and physicochemical the in vivo permeability of the BBB allows BBBoCs to be
microenvironmental factors. However, the main used in small-molecule drug screening.
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Volume 10 Issue 6 (2024) 160 doi: 10.36922/ijb.4166