3D-printed cell culture models for research into glioblastomas

An interdisciplinary team at the University Medical Center Würzburg has developed a 3D cell culture model that simulates the natural environment of a glioblastoma. The model makes it possible to study the interactions between tumor cells and healthy brain cells. The research is part of the Collaborative Research Center SFB TRR 225, which is funded by the German Research Foundation (DFG). The aim is to better understand the mechanisms of tumor growth and to develop new approaches for the treatment of these particularly aggressive brain tumors.

Glioblastomas are difficult-to-treat tumors with a high growth rate that infiltrate the surrounding brain tissue, making complete surgical removal difficult. They are also highly resistant to current therapeutic agents. To analyze the causes of this resistance, the 3D cell culture system was developed, which is based on neurons, astrocytes and tumor cells.

“We were able to show that this glioblastoma model simulates the tumor microenvironment and cell-cell interactions, as we know them from in vivo xenograft models, very well. This means that our 3D model realistically depicts the natural environment and the interactions between the cells, similar to experiments with living organisms. We can use the model to investigate and manipulate chemotherapeutic agents and their mechanism of action on tumor growth,” explains Mateo Andrade Mier.

One challenge during development was to create a stable 3D printing process for ultra-soft biomaterials. To solve this, special microfibers were used as scaffold structures that were populated with different cell types. This enabled long-term studies over several weeks. The researchers are now planning to expand the model with human cell types in order to gain even more precise findings.

The project is embedded in a comprehensive research network that combines expertise from the fields of materials science, biology and medicine. In addition to the University Medical Center Würzburg, scientists from the Universities of Erlangen-Nuremberg and Bayreuth are also involved. Their common goal is to develop new hydrogels and provide biofabricated tissue models for translational approaches in cancer research. The hydrogel for the model was developed at the Chair of Functional Materials in Medicine and Dentistry in Würzburg, while researchers at the Rudolf Virchow Center were responsible for the imaging characterization of the cell-matrix interactions.

Prof. Dr. Carmen Villmann, research group leader at the Institute of Clinical Neurobiology, explains the relevance: “By establishing a 3D cell culture model that has similar properties to the in vivo situation, we have provided an important building block for translational research to better understand the mechanisms of tumor growth and its containment.”

In the long term, the 3D cell culture model should contribute to a better understanding of the resistance mechanisms of glioblastomas and enable personalized therapeutic approaches. The combination of biofabrication, cell biology and imaging technologies offers promising prospects for the further development of treatment methods.