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International Journal of Bioprinting 3D bioprinting technology for brain tumor

of temozolomide (TMZ) and radiotherapy, resulting in an in complex organs, such as the brain. As mentioned
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overall survival rate of 14.6 months for patients with GBM. previously, the poor approach and complexity of multi-
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The combination of bevacizumab, an anti-angiogenic component interactions among various cell types limit
drug approved by the United States (US) Food and the scope of brain tumor studies. 3D-bioprinted neural
Drug Administration (FDA), with chemoradiotherapy systems, including neurons, microglia, and astrocytes,
markedly increased progression-free survival in patients can resolve previous limitations of neuronal tumor
with GBM in a phase 3 trial. However, it often recurs due study. Biomimetic GBM models with microfluidic chips
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to tumor heterogeneity, immune evasion, glioma stem recapitulate complex biological networks, including
cells, and drug efflux pumps. In particular, recent clinical brain tumors, the BBB, and neurotransmission; thus,
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studies have estimated the efficacy of some approaches they can be more useful than conventional models. 15,16
to avoid the blood–brain barrier (BBB) and accomplish Using gelatin methacrylate (GelMA) and glycidyl
efficient delivery in patients with recurrent GBM. methacrylate-hyaluronic acid (GMHA) hydrogels, digital
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Therefore, more patient-specific therapeutic approaches light processing (DLP)-based 3D bioprinting models
are required to improve the overall survival of patients with GBM ECM can mimic transcriptional profiles and
with GBM. immune cell composition with high quality. 9
For decades, general in vitro models for cancer 3D tumor models, including spheroids, organoids,
research, including 2D cancer and animal models, have biopolymer scaffolds, and tumor-on-a-chip models, are
been used to elucidate cancer mechanisms. 2D monolayer more indicative of human tumor properties, involving
cancer cell lines offer a hypothetical cancer environment hypoxic regions and a gradient distribution of chemical/
that imitates tumor characteristics, such as protein biological factors. The TME has implications for immune
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expression, cell signaling, and cell viability. However, interactions in GBM progression and intercellular
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the 2D culture model still has limitations in that it cannot crosstalk. Furthermore, by integrating GBM stem
perfectly reflect the actual tumor microenvironment cells (GSCs), the relation among GSCs, anticancer drug
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(TME) owing to the absence of an extracellular resistance, and vascularization can be identified. A
matrix (ECM). As animal models have immunological vascularized GBM-on-a-chip was designed to recapitulate
similarities to humans, these models are conducive to the pathophysiological states of tumors and the adjacent
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studying drug responses, tumorigenicity, and immune vascular microenvironments. It also interconnects with
responses. Animal models also have limitations in the porous membrane, which permits biochemical and
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demonstrating the complexity of human cancer, owing mechanical interactions, resulting in the generation of a
to issues, such as high cost, poor controllability, and dynamic GBM environment. In this review, we describe
immunodeficiency, in some species. 10 advanced 3D biomimetic models of brain tumors, especially
GBMs, and their therapeutic implications (Figure 1).
Advanced 3D bioprinting technology helps overcome
these limitations and enhances our understanding 2. Biomaterials and methods of
of the complexity of cancer. 3D bioprinting is an
emerging technology that can be used to construct the 3D bioprinting
biological organization of cancer using living cells, ECM 2.1. Biomaterials
components, and biochemical factors. Furthermore, 3D Recently, 3D bioprinting technologies that utilize various
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bioprinting can resolve challenges, such as drug delivery biomaterials and bioprinting methods have been developed,
and functional organ replacement. 3D tumor models opening the possibility of reconstructing individual
have been developed using various strategies, including components of the TME (Table 1). In particular, neuronal
inkjet-based bioprinting, micro-extrusion, and laser- microenvironments can be accurately constructed using
assisted bioprinting. 3D cancer models have various bioink and 3D printing methods. Given the various
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applications based on modeling parameters such as biocompatibilities and biodegradabilities of hydrogels,
extrusion pressure, nozzle diameter, and temperature. the selection of a proper hydrogel is pivotal prior to
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By modifying these printing parameters, cell viability can designing the TME of neural tissues and sustaining its
be optimized after printing. Computational simulation viability. Natural and synthetic substances are typically
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programs provide a better understanding of optimized utilized as bioinks, owing to their lack of toxicity and
printing parameters for post-printing environments. biocompatibility. In particular, gelatin- and fibrin-
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Moreover, co-printing bioink technology can provide based bioinks can strengthen cell functions because they
different cell types, ECM, and biomolecules for the are natural polymers with intrinsic binding sites. For
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construction and complexity of the TME. In particular, example, collagen-derived gelatin has been widely used
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these techniques contribute to the study of tumors clinically because of its excellent safety and functionality.
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Volume 10 Issue 6 (2024) 155 doi: 10.36922/ijb.4166