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International Journal of Bioprinting 3D bioprinting technology for brain tumor

6. Bioprinted patient-derived tissues for patient-derived tissues (PDTs). Lobaplatin, a platinum-
136
clinical drug responses based compound with antitumor activity in multiple
solid tumors, displays an average tumor inhibition rate of
Most in vitro studies are performed in 2D cell systems, over 50% in PDT models. 149,150 Interestingly, drug testing
and many drug candidates fail because 2D imaging does using PDTs demonstrated that most patients with tumor
not reflect the complexity of our bodies. 124,125 More than recurrence did not respond to TMZ treatment. Lomustine
95% of cases fail during clinical trials despite continuous (CCNU), an alkylating agent of the nitrosourea family,
research. Despite the availability of many effective drug exhibits higher efficacy in suppressing tumor cells in PDTs,
126
candidates, non-physiological systems hinder further specifically in patients with recurrent GBM. 151,152
research and optimization. However, bioprinting
127
facilitates the evaluation of drug responses in terms GlioML, a machine learning system that incorporates
of safety, efficacy, and personalized medicine before nine different algorithms, effectively differentiates
progressing to animal models (Table 2). 128,129 between World Health Organization grade III and IV
gliomas, indicating varying drug responses at different
Patient-specific bioinks were developed by mixing stages of the disease. Integrated 3D-bioprinted models
153
a prepolymer solution with a single-cell suspension. A and GlioML facilitated the prediction and evaluation of
bioink composed of GelMA and HA methacrylate was drug responses in individual patients (Figure 6). Three
loaded into the bioprinter and polymerized to produce GlioML compounds (RSL, dasatinib, and lovastatin) were

Table 2. Results of drug response test in glioblastoma (GBM) 3D models
Drug Related pathway Combination therapy Drug response FDA approval Reference
Temozolomide (TMZ) Nrf2/HO-1 pathway, Wnt/β- CCRT Different responses depend Yes 105,46,131
catenin signaling, ferroptosis on treatment resistance in
GBM-on-chips

O -benzylguanine (O BG) Damaged DNA repair CCRT Represses the survival rates No 105,132,133
6
6
mechanism of GBM-on-chips
Methoxyamine (MX) NAD+ salvage pathway No
Cisplatin AXL/PI3K/Akt/NF-κB KU60019 Different responses are Yes 105,133–135
signaling O BG exhibited by GBM-on-chips
6
obtained during surgery
Radiation before and from tumors after
treatment
Lobaplatin FUBP1/AA metabolic N/A Induces >50% tumor Yes 136–139
pathway, caspase-dependent inhibition in PDT models
pathway
Lomustine (CCNU) NER/FA pathway, N/A Inhibits tumor cell Yes 136,140–142
programmed cell death progression in PDTs
pathway model with high efficiency,
particularly in recurrent
glioblastoma
1S,3R-RSL-3 (RSL) Ferroptosis, UPR pathway TMZ Notably diminishes tumor No 136,142–148
Dasatinib Src pathway, STAT3 viability in treated PDTs Yes
signaling, AKT/ERK
signaling
Lovastatin NF-κB pathway, MAPK Yes
signaling, Akt/mTOR
signaling
Abbreviations: AA, Arachidonic acid; AKT, protein kinase B; CCRT, concurrent chemotherapy; ERK, extracellular signal-regulated kinase; FA, Fanconi
anemia; FUBP1, Far upstream element-binding protein 1; MAPK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; NAD+,
Nicotinamide adenine dinucleotide; NER, nucleotide excision repair; NF-κB, Nuclear factor kappa B; Nrf2/HO-1, nuclear factor erythroid-2-related
factor 2/heme oxygenase 1; PDT, patient-derived tissue; PI3K, Phosphatidylinositol 3-kinase; STAT3, signal transducer and activator of transcription 3;
Src, proto-oncogene tyrosine-protein kinase; UPR, unfolded protein response.

Volume 10 Issue 6 (2024) 164 doi: 10.36922/ijb.4166