A vascularized in vivo melanoma model suitable for metastasis research of different tumor stages using fundamentally different bioinks

Schmid, Rafael; Schmidt, Sonja K.; Schrüfer, Stefan; Schubert, Dirk W.; Heltmann-Meyer, Stefanie; Schicht, Martin; Paulsen, Friedrich; Horch, Raymund E.; Bosserhoff, Anja K.; Kengelbach-Weigand, Annika; Arkudas, Andreas

doi:10.1016/j.mtbio.2024.101071

Cited by 2 publications

(1 citation statement)

References 57 publications

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“…Bioinks are suitable for replicating the in vivo environment as accurately as possible 15 . These inks contain cells and hydrogels which consist largely of water and can be adapted to the tumor environment in terms of their composition, stiffness and diffusion properties thorough alterations of their composition.…”

Section: Introductionmentioning

confidence: 99%

Characterization of two different alginate-based bioinks and the influence of melanoma growth within

Schipka,

Heltmann-Meyer,

Schneidereit

et al. 2024

Sci Rep

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Extrusion-based bioprinting is an established method in biofabrication. Suitable bioinks have fundamentally different compositions and characteristics, which should be examined, in order to find a perfect model system. Here, we investigate the effect of two alginate-based, yet unalike 3D-printed bioinks, pre-crosslinked alginate-dialdehyde gelatin (ADA-GEL) and a mixture of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), on the melanoma cell line Mel Im and vice versa in terms of stiffness, shrinkage, cellular behavior and colony formation over 15 days. Rheological stiffness measurements revealed two soft gels with similar storage moduli. The cells did not have a significant impact on the overall stiffness, whereas ADA-GEL (2.5/2.5%) was significantly stiffer than Alg/HA/Gel (0.5/0.1/3%). Regarding the shrinkage of printed constructs, cells had a significant influence, especially in ADA-GEL, which has covalent bonds between the oxidized alginate and gelatin. Multi-photon microscopy exhibited proliferation, cell spreading and migration in ADA-GEL with cell–cell and cell–matrix interaction, dissimilarly to Alg/HA/Gel, in which cells formed spherical, encapsulated colonies. Scanning electron microscopy and histology showed degradation and multi-layered growth on ADA-GEL and fewer examples of escaped cells on Alg/HA/Gel. Both gels serve as proliferation bioink for melanoma with more necrosis in deeper Alg/HA/Gel colonies and differences in spreading and matrix interaction. These findings show the importance of proper characterization of the bioinks for different applications.

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Section: Introductionmentioning

confidence: 99%

Characterization of two different alginate-based bioinks and the influence of melanoma growth within

Schipka,

Heltmann-Meyer,

Schneidereit

et al. 2024

Sci Rep

Self Cite

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Pneumatic extrusion bioprinting-based high throughput fabrication of a melanoma 3D cell culture model for anti-cancer drug screening

de Villiers,

Kotzé,

du Plessis

2024

Biomed. Mater.

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The high incidence of malignant melanoma highlights the need for in vitro models that accurately represent the tumour microenvironment, enabling developments in melanoma therapy and drug screening. Despite several advancements in 3D cell culture models, appropriate melanoma models for evaluating drug efficacy are still in high demand. The 3D pneumatic extrusion-based bioprinting technology offers numerous benefits, including the ability to achieve high-throughput capabilities. However, there is a lack of research that combines pneumatic extrusion-based bioprinting with analytical assays to enable efficient drug screening in 3D melanoma models. To address this gap, this study developed a simple and highly reproducible approach to fabricate a 3D A375 melanoma cell culture model using the pneumatic extrusion-based bioprinting technology. To optimise this method, the bioprinting parameters for producing 3D cell cultures in a 96-well plate were adjusted to improve reproducibility while maintaining the desired droplet size and a cell viability of 92.13± 6.02%. The cross-linking method was optimised by evaluating cell viability and proliferation of the 3D bioprinted cells in three different concentrations of calcium chloride. The lower concentration of 50 mM resulted in higher cell viability and increased cell proliferation after 9 days of incubation. The A375 cells exhibited a steadier proliferation rate in the 3D bioprinted cell cultures, and tended to aggregate into spheroids, whereas the 2D cell cultures generally formed monolayered cell sheets. In addition, we evaluated the drug responses of four different anti-cancer drugs on the A375 cells in both the 2D and 3D cell cultures. The 3D cell cultures exhibited higher levels of drug resistance in all four tested anti-cancer drugs. This method presents a simple and cost-effective method of producing and analysing 3D cell culture models that do not add additional complexity to current assays and shows considerable potential for advancing 3D cell culture models' drug efficacy evaluations.

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A vascularized in vivo melanoma model suitable for metastasis research of different tumor stages using fundamentally different bioinks

Cited by 2 publications

References 57 publications

Characterization of two different alginate-based bioinks and the influence of melanoma growth within

Characterization of two different alginate-based bioinks and the influence of melanoma growth within

Pneumatic extrusion bioprinting-based high throughput fabrication of a melanoma 3D cell culture model for anti-cancer drug screening

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