Tumor Cells Develop Defined Cellular Phenotypes After 3D-Bioprinting in Different Bioinks.

Sonja K Schmidt,Rafael Schmid,Annika Kengelbach-Weigand,Andreas Arkudas,Anja K Bosserhoff

doi:10.3390/cells8101295

Sonja K Schmidt, Rafael Schmid + Show 3 more

Open Access

https://doi.org/10.3390/cells8101295

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Abstract

Malignant melanoma is often used as a model tumor for the establishment of novel therapies. It is known that two-dimensional (2D) culture methods are not sufficient to elucidate the various processes during cancer development and progression. Therefore, it is of major interest to establish defined biofabricated three-dimensional (3D) models, which help to decipher complex cellular interactions. To get an impression of their printability and subsequent behavior, we printed fluorescently labeled melanoma cell lines with Matrigel and two different types of commercially available bioinks, without or with modification (RGD (Arginine-Glycine-Aspartate)-sequence/laminin-mixture) for increased cell-matrix communication. In general, we demonstrated the printability of melanoma cells in all tested biomaterials and survival of the printed cells throughout 14 days of cultivation. Melanoma cell lines revealed specific differential behavior in the respective inks. Whereas in Matrigel, the cells were able to spread, proliferate and form dense networks throughout the construct, the cells showed no proliferation at all in alginate-based bioink. In gelatin methacrylate-based bioink, the cells proliferated in clusters. Surprisingly, the modifications of the bioinks with RGD or the laminin blend did not affect the analyzed cellular behavior. Our results underline the importance of precisely adapting extracellular matrices to individual requirements of specific 3D bioprinting applications.

Highlights

Regardless of constantly evolving possibilities for cancer treatments, there is still a huge demand for therapies offering a better outcome
The GelXA bioinks are made up of gelatin methacrylate, xanthan gum, and alginate, and one further coupled with laminin (GelXA Laminink+). Those modifications were chosen, as the expression of suitable receptor proteins like integrins is well described in malignant melanoma and found to be of importance for tumor growth and progression [31]
The tumor microenvironment (TME) is composed of different cell types, including stem cells, fibroblasts and immune cells, blood vessels, soluble factors and the extracellular matrix (ECM), which all contribute to cellular behavior and thereby to cancer disease

Summary

Introduction

Regardless of constantly evolving possibilities for cancer treatments, there is still a huge demand for therapies offering a better outcome. A commonly used model tumor for the development of new therapies is melanoma, a highly malignant tumor type derived from melanocytes and characterized by extremely early and fast metastasis from the primary tumor and subsequent fast progression. Many aspects of tumor formation and progression remain cryptic until today, hampering the development of novel approaches. This is due to the high complexity of the molecular processes within the biological systems and owed to often simplified disease models, like two-dimensional (2D) cell culture, which are commonly used in basic research. The existing 2D systems have helped to elucidate the six hallmarks of cancer [1] and support the process in developing cancer therapies

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