Abstract
Bioprinting offers the opportunity to fabricate precise 3D tumor models to study tumor pathophysiology and progression. However, the choice of the bioink used is important. In this study, cell behavior was studied in three mechanically and biologically different hydrogels (alginate, alginate dialdehyde crosslinked with gelatin (ADA–GEL), and thiol-modified hyaluronan (HA-SH crosslinked with PEGDA)) with cells from breast cancer (MDA-MB-231 and MCF-7) and melanoma (Mel Im and MV3), by analyzing survival, growth, and the amount of metabolically active, living cells via WST-8 labeling. Material characteristics were analyzed by dynamic mechanical analysis. Cell lines revealed significantly increased cell numbers in low-percentage alginate and HA-SH from day 1 to 14, while only Mel Im also revealed an increase in ADA–GEL. MCF-7 showed a preference for 1% alginate. Melanoma cells tended to proliferate better in ADA–GEL and HA-SH than mammary carcinoma cells. In 1% alginate, breast cancer cells showed equally good proliferation compared to melanoma cell lines. A smaller area was colonized in high-percentage alginate-based hydrogels. Moreover, 3% alginate was the stiffest material, and 2.5% ADA–GEL was the softest material. The other hydrogels were in the same range in between. Therefore, cellular responses were not only stiffness-dependent. With 1% alginate and HA-SH, we identified matrices that enable proliferation of all tested tumor cell lines while maintaining expected tumor heterogeneity. By adapting hydrogels, differences could be accentuated. This opens up the possibility of understanding and analyzing tumor heterogeneity by biofabrication.
Highlights
Various types of cancers become an increasing problem in our aging society
We focused on the effects of the hydrogels on cell survival, metabolic activity, and growth, comparing tumor cells of different origin and different subtypes
1% m/v and 3% m/v; alginate dialdehyde (ADA)–GEL was used in 2.5% m/v and 4% m/v; HA-SH was used with 0.8% m/v
Summary
Various types of cancers become an increasing problem in our aging society. Nowadays, one out of eight women in the USA develops breast cancer and approximately 3% of non-Hispanic white people develop invasive melanoma [1]. Three-dimensional (3D) tumor models are needed for basic and applied research on tumor progression, drug efficacy, and development of resistance. There are many variables to consider when creating experimental models that are functional, reliable, and reproducible, as the tumor microenvironment consists of a complex extracellular matrix (ECM), tumor-associated cells, vasculature, and a variety of cytokines [7]. It is possible to arrange varying matrix and cell conditions Such 3D models would enable the tumor cells to adopt different phenotypes that mimic the in vivo situation appropriately [10]. The ECM between different tumors varies greatly; there are many common features, e.g., in both melanoma and breast cancer, laminin 5-γ2 chain and hyaluronic acid (hyaluronan, HA) are highly expressed [11]
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