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International Journal of Bioprinting Biomimetic biofabrication of tumors volume

observed patient-specific resistances after concurrent originating in other sites and metastasize to the skeleton
chemoradiation using temozolomide . are as secondary . Both tumor types are characterized by
[78]
[84]
a composite microenvironment that comprises an array
4.3. Lung cancer of elements, including mechanical and architectural cues,
Cancerous lung tissue is highly aggressive, forming signaling proteins, and interactions between the bone
fibrotic aggregates that can impede the physiological tumor and the stromal cells, that overall impact growth,
functionality of the lungs. There is an urgent need for drug sensitivity, and ultimately therapy outcome .
[85]
physiological models that can resemble lung cancerous
microenvironments for the rapid and efficacious testing Particularly, primary bone tumors, also known as
of anti-tumor drugs. Bioprinting can aid the modeling of bone sarcomas, are rare malignant tumors characterized
[86]
pathological conditions of the lung to mimic the intricate by the uncontrolled growth of cells within the bone .
interwoven vascular and epithelial networks . The current standard treatment protocol is composed
[79]
of the association of surgery with adjuvant and/or
In this context, Han et al. recently built a 3D-bioprinted neoadjuvant multi-agent chemotherapy, which leads to
[80]
vascularized tumor model which involved the fabrication a 5-year survival for the most common malignant bone
of a blood vessel layer obtained through the printing and tumors of around 70% . Conventional malignant bone
[87]
culturing of HUVECs and lung fibroblasts in a gelatin/ sarcomas include: (i) osteosarcoma (OS), localized in the
alginate/fibrinogen hydrogel, followed by seeding multi- metaphysis of the long bone in adolescents near the growth
cellular MCTS onto the pre-formed layer. The sprouting plate; (ii) Ewing’s sarcoma, most commonly localized
of new blood vessels occurred in the surroundings of in the pelvis, legs, or arms of children and young adults;
spheroids, driving their increase in dimensions over time. and (iii) chondrosarcoma, usually confined in the pelvis,
Noticeably, treatment with temozolomide (an alkylating legs, or arms in middle-aged and older adults, where
anti-tumor agent) and sunitinib (angiogenic inhibitor) the cancerous cells produce cartilage . The majority
[88]
resulted to be more successful than temozolomide alone in of primary bone tumor models have been developed,
targeting spheroids surrounded by vessel network . attempting to recapitulate OS features and pathophysiology
[80]
In another study, Mondal et al. developed a similar in vitro. Indeed, OS is the most common sarcoma, and it is
[81]
biomaterial ink (comprising gelatin and alginate) to embed characterized by cancerous cells producing woven bone.
and print non-small cell lung cancer (NSCLC) PDX cells While mature bone is composed of sparse osteocytes,
and lung CAFs co-cultures. The bioprinted co-culture conventional OS consists of densely populated tissue
models enabled the formation of MCTS and cellular with cells that exhibit osteo-, chondro-, or fibroblastic
[89]
crosstalk through the upregulation of α-SMA, vimentin, phenotype .
and loss of E-cadherin . 3D bioprinting has been recently applied to the
[81]
treatment of OS [90,91] as well as the generation of OS
A recent study by Dong et al. engineered a novel [92-94]
[82]
droplet-based approach to 3D-bioprint lung cancer models . Multiple studies have used OS cell lines for
organoids in a high-throughput fashion for rapid drug biocompatibility evaluation and as proliferation models
in lieu of OS model engineering . Indeed, only a limited
[95]
testing. The alginate and hyaluronic acid-based material ink number of 3D-bioprinted models have been ultimately
was functionalized with RGD groups, further stimulating fabricated to recapitulate the complex primary bone
the functionality post-printing. In comparison with 2D TME in vitro [91,96] . In early attempts to replicate OS TME,
control, the 3D-printed organoid system demonstrated Neufurth et al. biofabricated a composite ink comprising
[97]
higher viability and ultimate functionality with an alginate/gelatin mixture for encapsulating and printing
expression of P-CK, MUC1, and caveolin-1.
Saos-2 cells. The use of a further coating prepared from
Using a digital light processing approach, Mei et al. agarose and calcium salt polyphosphate [polyphosphate
[83]
2+
fabricated a new perfusable 3D lung cancer model (polyP)·Ca -complex] was found to actively promote the
[97]
(Figure 4c) with NSCLC cells for screening anti-cancer proliferation and, in conjunction with bioactive glass
[98]
drug candidates and investigating the effects of gemcitabine nanoparticles , the ability to mineralize cancer cells
in static and dynamic conditions. They Mei and colleagues (Figure 4d).
found a significant drug-mediated effect, confirming the
safety and efficacy potential of such model. 4.5. Modeling vasculature in 3D-bioprinted
cancer models
4.4 Bone cancer The presence of a functional vascular network is pivotal
Bone tumors arising in the bone or from bone-derived for the growth and survival of cancerous tissues. Typically,
cells and tissues are classified as primary and those vascularization plays a critical role in (i) supplying oxygen,

Volume 9 Issue 6 (2023) 382 https://doi.org/10.36922/ijb.1022