Transactions on Additive Manufacturing Meets Medicine
Vol. 6 No. S1 (2024): Trans. AMMM Supplement
https://doi.org/10.18416/AMMM.2024.24091862

Material Properties, Structural Designs, and Printing Technologies, ID 1862

Development of a 3D-bioprinted drug screening system for personalized glioblastoma treatment

Main Article Content

Philipp Kaps (Department of Medicine, Clinic III—Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany), Thomas Freitag (Department of Medicine, Clinic III—Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany), Christian Polley (Chair of Microfluidics, University of Rostock, Rostock, Germany), Leonora Calopresti (Chair of Microfluidics, University of Rostock, Rostock, Germany), Emily Zunke (Department of Medicine, Clinic III—Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany), Justus Ramtke (Department of Medicine, Clinic III—Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany), Marcus Frank (1) Department Life, Light & Matter, University of Rostock, Rostock, Germany 2) Medical Biology and Electron Microscopy Centre, Rostock University Medical Center, Rostock, Germany), Piotr Grabarczyk (Dept. of Internal Medicine, Clinic III-Hematology, Oncology, University Medicine Greifswald, Greifswald, Germany), Sascha Troschke-Meurer (Department of Pediatric Oncology and Hematology, University Medicine Greifswald, Greifswald, Germany), Daniel Dubinski (Department of Neurosurgery, Rostock University Medical Center, Rostock, Germany), Thomas Freiman (Department of Neurosurgery, Rostock University Medical Center, Rostock, Germany), Hermann Seitz (1) Chair of Microfluidics, University of Rostock, Rostock, Germany 2) Department Life, Light & Matter, University of Rostock, Rostock, Germany), Christian Junghanss (Department of Medicine, Clinic III—Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany), Claudia Maletzki (Department of Medicine, Clinic III—Hematology, Oncology, Palliative Medicine, Rostock University Medical Center, Rostock, Germany)

Abstract

Background: Central Nervous System WHO grade 4 glioblastoma is a highly malignant brain tumor with a poor prognosis. The complex three-dimensional architecture of glioblastoma, consisting of cell-cell and cell-matrix assemblies of tumor cells, stromal cells, and extracellular matrix contributes to a highly dynamic microenvironment that resists current therapeutic approaches. Here, we established a 3D biomimetic bioprinting approach with patient-derived glioblastoma cell lines to mimic the natural tumor microenvironment for preclinical targeted therapy. Methods: Two different hydrogels (Alginate/Gelatine 3%/15%, GelMa, 4%) were used to evaluate biocompatibility. Patient-derived iRFP-680-transduced glioblastoma cells were suspended in the hydrogels and printed into scaffolds. Tumor cell growth and viability within the scaffolds were monitored for 28-days. Scanning electron microscopy was performed for structural analysis. A preliminary treatment approach was done with the standard of care drug temozolomide (TMZ 10 µM) and the CDK4/6 inhibitor abemaciclib (1 µM). Viability and LDH release were quantified. Results & Conclusion: The hydrogel compositions showed good printability. A direct comparison between the two hydrogels showed a comparable growth pattern, i.e. constant growth over a period of 21 days and a steady state until day 28. Scanning electron microscopy confirmed cellular integrity within the scaffold and the formation of small cell clusters with large pores within the matrix. In a preliminary drug response analysis, we successfully confirmed our previous results from 2D and 3D cultures. The preliminary 3D biomimetic bioprinting model proved to be a promising platform with good cell-material interaction for nutrient and substance exchange. For advanced preclinical drug screening, we aim to improve the culture conditions by incorporating vessels, non-malignant microglia and astrocytes, and by applying dynamic cell culture conditions.

Article Details

How to Cite

Kaps, P., Freitag, T., Polley, C., Calopresti, L., Zunke, E., Ramtke, J., … Maletzki, C. (2024). Development of a 3D-bioprinted drug screening system for personalized glioblastoma treatment. Transactions on Additive Manufacturing Meets Medicine, 6(S1), 1862. https://doi.org/10.18416/AMMM.2024.24091862