3D-Engineered Scaffolds to Study Microtubes and Localization of Epidermal Growth Factor Receptor in Patient-Derived Glioma Cells

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Abstract

A major obstacle in glioma research is the lack of in vitro models that can retain cellular features of glioma cells in vivo. To overcome this limitation, a 3D-engineered scaffold, fabricated by two-photon polymerization, is developed as a cell culture model system to study patient-derived glioma cells. Scanning electron microscopy, (live cell) confocal microscopy, and immunohistochemistry are employed to assess the 3D model with respect to scaffold colonization, cellular morphology, and epidermal growth factor receptor localization. Both glioma patient-derived cells and established cell lines successfully colonize the scaffolds. Compared to conventional 2D cell cultures, the 3D-engineered scaffolds more closely resemble in vivo glioma cellular features and allow better monitoring of individual cells, cellular protrusions, and intracellular trafficking. Furthermore, less random cell motility and increased stability of cellular networks is observed for cells cultured on the scaffolds. The 3D-engineered glioma scaffolds therefore represent a promising tool for studying brain cancer mechanobiology as well as for drug screening studies.

Original languageEnglish
Article number2204485
Number of pages14
JournalSmall
Volume18
Issue number49
Early online date7 Oct 2022
DOIs
Publication statusPublished - 8 Dec 2022

Bibliographical note

Funding Information:
P.J.F. and A.A. contributed equally to this work. Part of this work was supported by a grant from the Brain Tumour Charity (Grant No. ET_2019__2_10470) and the ErasmusMC Academic Centre of Excellence “Tumor Immunology and Immune Therapy” and the TU Delft Bioengineering Institute MSc Grant. The authors would like to acknowledge P. A. E. Sillevis Smitt (Neurology Department, Erasmus Medical Center (Erasmus MC)) and U. Staufer (Department of Precision and Microsystems Engineering (PME), Delft University of Technology (TU Delft)) for their insightful comments. The authors’ sincerely thank G. van Cappellen (Erasmus Optical Imaging Center, Erasmus MC) for his assistance in immunofluorescence imaging and image analysis. Special thanks to A. Sharaf (PME, TU Delft) for his help with 2PP fabrication and S. Aghajani (PME, TU Delft) for his help with SEM. The authors would also like to acknowledge the assistance of TU Delft PME laboratory staff specially G. Emmaneel for his help with laser cutting. The authors are grateful to the TU Delft Micro and Nano Engineering and the Erasmus MC Neuro‐Oncology research groups for their kind support.

Funding Information:
P.J.F. and A.A. contributed equally to this work. Part of this work was supported by a grant from the Brain Tumour Charity (Grant No. ET_2019__2_10470) and the ErasmusMC Academic Centre of Excellence “Tumor Immunology and Immune Therapy” and the TU Delft Bioengineering Institute MSc Grant. The authors would like to acknowledge P. A. E. Sillevis Smitt (Neurology Department, Erasmus Medical Center (Erasmus MC)) and U. Staufer (Department of Precision and Microsystems Engineering (PME), Delft University of Technology (TU Delft)) for their insightful comments. The authors’ sincerely thank G. van Cappellen (Erasmus Optical Imaging Center, Erasmus MC) for his assistance in immunofluorescence imaging and image analysis. Special thanks to A. Sharaf (PME, TU Delft) for his help with 2PP fabrication and S. Aghajani (PME, TU Delft) for his help with SEM. The authors would also like to acknowledge the assistance of TU Delft PME laboratory staff specially G. Emmaneel for his help with laser cutting. The authors are grateful to the TU Delft Micro and Nano Engineering and the Erasmus MC Neuro-Oncology research groups for their kind support.

Publisher Copyright:
© 2022 The Authors. Small published by Wiley-VCH GmbH.

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