A 3D Collagen-Based Bioprinted Model to Study Osteosarcoma Invasiveness and Drug Response

Pellegrini, Evelin; Desando, Giovanna; Petretta, Mauro; Cellamare, Antonella; Cristalli, Camilla; Pasello, Michela; Manara, Maria Cristina; Grigolo, Brunella; Scotlandi, Katia

doi:10.3390/polym14194070

Cited by 7 publications

(7 citation statements)

References 40 publications

(44 reference statements)

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“…The full search is illustrated in the PRISMA flowchart ( Figure 2 ) . Finally, 70 studies fulfilling the inclusion/exclusion criteria were included in this review [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 6...…”

Section: Resultsmentioning

confidence: 99%

“…HA and TCP (both comprising calcium/phosphate) are widely used in bone research owing to their excellent biocompatibility, chemical resemblance to native bone mineral, and capacity to promote the attachment, migration, proliferation, and differentiation of bone cells [ 32 , 51 , 59 ]. Three-dimensional collagen-based models were used to elicit OS invasiveness [ 27 , 28 ], therapeutic responses [ 27 , 28 , 60 ], and better mimicry of ECM for osteoblastic cultivation [ 63 ]. Collagen demonstrates excellent biodegradability and biocompatibility properties [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

“…( C ) Comparison of IC 50 and the ratio between 3D and 2D for drugs other than the MAP drugs. Details of various OS cell lines and types of 3D OS models used (scaffold-based vs. scaffold-free) are included [ 13 , 14 , 22 , 25 , 28 , 29 , 58 ].…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review

Sandhu,

Bakkalci,

Wei

et al. 2023

Cancers

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This scoping review evaluated 3D osteosarcoma (OS) models’ biomimicry, examining their ability to mimic the tumour microenvironment (TME) and their drug sensitivity. Adhering to PRISMA-ScR guidelines, the systematic search revealed 293 studies, with 70 selected for final analysis. Overall, 64% of 3D OS models were scaffold-based, compared to self-generated spheroid models. Scaffolds generated using native matrix were most common (42%) with collagen I/hydroxyapatite predominating. Both scaffold-based and scaffold-free models were used equally for drug screening. The sensitivity of cancer cells in 3D was reported to be lower than that of cells in 2D in ~90% of the drug screening studies. This correlates with the observed upregulation of drug resistance. OS cells cultured in extracellular matrix (ECM)-mimetic scaffolds and native biomaterials were more resistant than cells in 2D. Co-cultures of OS and stromal cells in 3D models enhanced osteogenic differentiation, ECM remodelling, mineralisation, and angiogenesis, suggesting that tumour–stroma crosstalk promotes disease progression. Seven studies demonstrated selective toxicity of chemotherapeutics towards OS cells while sparing stromal cells, providing useful evidence for developing biomimetic tumour–stroma models to test selective drug toxicity. In conclusion, this review highlights the need to enhance biomimicry in 3D OS models for TME recapitulation, especially in testing novel therapeutics. Future research should explore innovative 3D biomimetic models, biomaterials, and advancements in personalised medicine.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review

Sandhu,

Bakkalci,

Wei

et al. 2023

Cancers

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“…The use of 3D bioprinting as a research tool in pediatric cancers is uncommon. In the few previous reports, researchers have primarily utilized osteosarcoma, glioblastoma, and neuroblastoma [ 13 , 34 , 35 ] . In neuroblastoma, bioprinting studies were not focused on its use as cancer models but rather on the potential to generate artificial neural networks and the ability of tumor cells to differentiate into viable, differentiated neural cells in sodium alginate gel [ 36 - 39 ] .…”

Section: Discussionmentioning

confidence: 99%

Using 3D-bioprinted models to study pediatric neural crest-derived tumors

Quinn¹,

Beierle²,

Julson³

et al. 2024

IJB

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The use of three-dimensional (3D) bioprinting has remained at the forefront of tissue engineering and has recently been employed for generating bioprinted solid tumors to be used as cancer models to test therapeutics. In pediatrics, neural crest-derived tumors are the most common type of extracranial solid tumors. There are only a few tumor-specific therapies that directly target these tumors, and the lack of new therapies remains detrimental to improving the outcomes for these patients. The absence of more efficacious therapies for pediatric solid tumors, in general, may be due to the inability of the currently employed preclinical models to recapitulate the solid tumor phenotype. In this study, we utilized 3D bioprinting to generate neural crest-derived solid tumors. The bioprinted tumors consisted of cells from established cell lines and patient-derived xenograft tumors mixed with a 6% gelatin/1% sodium alginate bioink. The viability and morphology of the bioprints were analyzed via bioluminescence and immunohisto chemistry, respectively. We compared the bioprints to traditional two-dimensional (2D) cell culture under conditions such as hypoxia and therapeutics. We successfully produced viable neural crest-derived tumors that retained the histology and immunostaining characteristics of the original parent tumors. The bioprinted tumors propagated in culture and grew in orthotopic murine models. Furthermore, compared to cells grown in traditional 2D culture, the bioprinted tumors were resistant to hypoxia and chemotherapeutics, suggesting that the bioprints exhibited a phenotype that is consistent with that seen clinically in solid tumors, thus potentially making this model superior to traditional 2D culture for preclinical investigations. Future applications of this technology entail the potential to rapidly print pediatric solid tumors for use in high-throughput drug studies, expediting the identification of novel, individualized therapies.

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“…As a confirmation, we found that confocal microscopy with automated counting provides superior accuracy and faster performance for quantifying viable cells in bioprinted constructs compared to standard fluorescence microscopy. As an example, a recent bioprinted osteosarcoma model for drug screening used indirect markers like Ki-67 and qualitative confocal analysis [26]. Also in such cases, automated confocal image analysis or multifocal microscopy may enable direct evaluation of drug effects on viability, greatly improving results reliability.…”

Section: Discussionmentioning

confidence: 99%

Advantages and limitations of using cell viability assays for 3D bioprinted constructs

Avnet,

Pompo,

Borciani

et al. 2024

Biomed. Mater.

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Bioprinting shows promise for bioengineered scaffolds and 3D disease models, but assessing the viability of embedded cells is challenging. Conventional assays are limited by the technical problems that derive from using multi-layered bioink matrices dispersing cells in three dimensions. In this study, we tested bioprinted osteogenic bioinks as a model system. Alginate- or gelatin-based bioinks were loaded with/without ceramic microparticles and osteogenic cells (bone tumour cells, with or without normal bone cells). Despite demonstrating 80-90% viability through manual counting and live/dead staining, this was time-consuming and operator-dependent. Moreover, for the alginate-bioprinted scaffold, cell spheroids could not be distinguished from single cells. The indirect assay (alamarBlue), was faster but less accurate than live/dead staining due to dependence on hydrogel permeability. Automated confocal microscope acquisition and cell counting of live/dead staining was more reproducible, reliable, faster, efficient, and avoided overestimates compared to manual cell counting by optical microscopy. Finally, for 1.2 mm-thick 3D bioprints, dual-photon confocal scanning with vital staining greatly improved the precision of the evaluation of cell distribution and viability and cell-cell interactions through the z-axis. In summary, automated confocal microscopy and cell counting provided superior accuracy for the assessment of cell viability and interactions in 3D bioprinted models compared to most commonly and currently used techniques

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A 3D Collagen-Based Bioprinted Model to Study Osteosarcoma Invasiveness and Drug Response

Cited by 7 publications

References 40 publications

Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review

Enhanced Biomimetics of Three-Dimensional Osteosarcoma Models: A Scoping Review

Using 3D-bioprinted models to study pediatric neural crest-derived tumors

Advantages and limitations of using cell viability assays for 3D bioprinted constructs

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