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
Number of pages14
JournalSmall
DOIs
Publication statusE-pub ahead of print - 7 Oct 2022

Bibliographical note

Acknowledgements
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.

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

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