Page 388 - IJB-9-6

International Journal of Bioprinting Biomimetic biofabrication of tumors volume

4.1. Breast cancer 4.2. Central nervous system tumors
Breast cancer is among the deadliest malignancies affecting Glioblastoma (GBM) is the most common malignant
women worldwide, progressing through specific stages primary brain cancer worldwide . The incidence GBM
[73]
from epithelial hyperproliferation to metastasis. Modeling is lower compared with other primary cancers, but it is
3D breast cancer TME has proved to be effective for drug particularly aggressive and impactful for the patients’ quality
testing and emulating drug resistance mechanisms. of life. Thus, the urgency for new therapeutic treatments is
Ling et al. used a custom-built bioprinting system to recently fueling the engineering of functional GBM models.
[68]
print sacrificial gelatin arrays as templates for fabricating Recently, Campos et al. developed a 3D-bioprinted
[74]
concave wells and in situ seeding of breast cancer cells to neuroblastoma model by printing human bone marrow-
form cellular spheroids in a controlled and high-throughput derived epithelial-neuroblastoma immortalized cells
manner (Figure 4a). Similarly, Zhou et al. employed the (SH-SY5Y), human primary umbilical cord-derived
[69]
same method to fabricate bone matrices composed of mesenchymal stromal cells (UC-MSC), and primary
gelatin methacryloyl (GelMA) and nano hydroxyapatite human umbilical vein endothelial cells (HUVECs) with
(nHA) and observed the interaction between breast cancer a collagen type I-based biomaterial ink. Cancer cells
cells and stromal cells (hFOB cells and MSCs). Relevantly, within the bioprinted constructs showed the formation
breast cancer cells were found to inhibit cell proliferation of Homer–Wright-like rosettes (phenotypic hallmark of
of osteoblasts and MSCs. Vascular endothelial growth neuroblastomas) and produced vimentin-rich matrices
factor (VEGF) was found overexpressed and secreted (characteristic of an aggressive phenotype), triggered by
by breast cancer cells with associated decreased alkaline the presence of MSCs within the bioprinted model .
[74]
phosphatase (ALP) activity of osteoblasts . Jiang et al.
[69]
[70]
used a composite hydrogel biomaterial ink, composed of Dai et al. employed a similar ink system composed of
gelatin and alginate, to embed and subsequently extrude gelatin, alginate, and fibrinogen, to embed glioma stem
breast cancer cells and cancer-associated fibroblasts cells and build a 3D-bioprinted model by mimicking the
(CAFs). The bioprinted co-culture models were able to brain tumor microenvironment. The 3D-bioprinted model
provide a biomimetic environment for more than 30 days exhibited higher resistance to temozolomide (an alkylating
and showed the formation of MCTS after 7 days of co- anti-tumor agent) compared to 2D culture models and
culture. Moreover, after 15 days of co-culture, fibroblasts higher expression of nestin and VEGF, showing the
migrated through a non-cell region of the hydrogel matrix vascularization potential of glioma stem cells .
[75]
and infiltrated the MCTS .
[70]
Similarly, Heinrich et al. developed a platform to
[76]
Recently, the modeling of the immune response to breast study the interaction between glioblastoma cells and
cancer progression has been modeled by Grolman et al. , macrophages. With the fabrication of bioprinted mini-
[71]
who fabricated vessel-like structures by extruding peptide- brains, a highly controlled TME was engineered to recruit
conjugated alginate under controlled flow rates. The core GBM-associated macrophages (GAM) and polarize them
of the fibers was filled with macrophages (RAW 264.7 into a GAM-specific phenotype. Furthermore, the study
mouse macrophages), while tumor cells (MDA-MB-231 demonstrated how therapeutics that inhibit the interaction
human breast adenocarcinoma cells) were incorporated between GAMs and glioblastoma cells lead to diminished
in the surrounding peptide-modified alginate to support tumor growth and reduced chemoresistance .
[76]
cell adhesion. By changing the architecture of the fibers,
[77]
these highly tunable models allowed to investigate the Recently, Monferrer et al. used a 3D-bioprinted
interactions between tumor cells and other cell types of the platform, based on malignant neuroblastic cells and
TME and could be useful in resembling vasculature and hydrogels made from GelMA and different percentages
modeling metastasis . of methacrylated alginate (AlgMA), to study the effects
[71]
of ECM stiffness on neuroblastic cells over time. Their
Reid et al. developed a platform to investigate findings showed an increase in cell proliferation, mRNA
[72]
tumorigenesis and the process of TME control of breast metabolism, and anti-apoptotic activity with stiffness,
cancer. A 3D collagen-based model was engineered, to while cell cluster density and occupancy decreased .
[77]
incorporate breast cancer cells and mammary epithelial
cells to drive tumoroid and chimeric organoids formation. Furthermore, Yi et al. used 3D bioprinting to fabricate
[78]
The TME-driven mechanism of epigenetic alterations of a 3D GBM model consisting of patient-derived tumor
cancer cells within chimeric organoids was confirmed cells, vascular endothelial cells, and decellularized ECM
by a significant increase in 5-hydroxymethylcytosine (an in order to recapitulate the main features of native GBM
intermediate of active DNA demethylation process) levels (Figure 4b). Using this platform, the authors observed
compared to tumoroids . that this model produced evidence that matched clinically
[72]
Volume 9 Issue 6 (2023) 380 https://doi.org/10.36922/ijb.1022