Glioblastoma (GBM) represents one of the most malignant brain tumors., developing from complex biochemical interactions between malignant and non-malignant cells, with the latter playing a relevant role since the early phases of cancer progression. These cell-cell interactions result into a three-dimensional (3D) microenvironment, hardly obtainable in vitro due to its high complexity.
3D models mimicking in vivo cellular behavior provide relevant information on tumor development and response to novel pharmacological, physical, and immunological therapies. However, currently available techniques do not enable 3D co-culture system assembly and structuring on demand, and thus they do not allow a strikingly precise spatiotemporal control of the interactions among different cell types. To date, a generation of devices supporting activities of biomedical research laboratories and pharmaceutical companies, by enabling a straightforward assembly of different cell types into a biomimetic 3D co-culture system, is indeed missing. In this regard, the development of 3D co-culture systems recapitulating the GBM microenvironment would represent a valuable opportunity to investigate the unclear origins and causes of this tumor. Most importantly, such multicellular model mimicking the complexity of the GBM niche would enable performing high-throughput tests with innovative anticancer drugs, as well as with other therapies (e.g. antiangiogenic treatments) involving non-malignant cells (e.g. neuronal/glial progenitors, astrocytes, microglia, and endothelial cells) that support tumor growth.
Two-photon lithography (TPL) represents an innovative technology, which allows fast prototyping of 3D structures with nanometer resolution for many applications. This microfabrication approach is exploited to reproduce different 3D microenvironments, featured by several physio-pathologic conditions. In MagDock, we proposed a 3D multi-culture system on magnetic scaffold self-assembly, faithfully mimicking GBM microenvironment complexity (Figure 1). Specifically, modular magnetic structures bear GBM cells, neuronal cells, and endothelial cells. Tumor core will be obtained by culturing GBM cells inside a magnetic scaffold shaped like a great dodecahedron. Healthy cells are instead cultured on tetrahedron-shaped magnetic scaffolds, that assemble around the tumor core by interfacing to its complementary indentations and thanks to magnetic interactions. Finally, vascular-mimicking tubular structures, serving as scaffolds for endothelial cells, assemble on the external part of the 3D multicellular system to mimic the presence of the blood-brain barrier.
This proof-of-concept prototype has been exploited to perform tests on a representative chemotherapy drug, allowing the evaluation of anticancer effects on malignant cells and side-effects on non-malignant cells associated with the tumor.
