In most in vitro cell models, cultures are made adhering to flat culture slides and the expected activation of specific cell markers is measured on cells. However, in this simplified condition, cell response is not representative of the in vivo response, which is based on cell interactions that occur in three-dimensional (3D) non-flat environments and between several cell populations. In oncology, 3D cell culture models are being exploited in particular during the process of the development of new anticancer agents, as they more reliably mimic the main features of human solid tumors, i.e., their structural organization, cellular layered assembling, hypoxia, and nutrient gradients. Recent evidences show as microgravity could provide appropriate cues to 3D cancer cell cultures, so that they can exhibit features that closer to the physio/pathological conditions. However, up to now there is no evidence in the literature about the combination of the microgravity effects on cancer cells combined to appropriate topographical environment surrounding the cancer models. In this project, we want to use a miniaturized 3D scaffold to bring into proof of concept our idea that cell culture experiments can be performed in more realistic 3D environments also on orbit. We will use a microfabricated scaffold called NICHOID, only 30 µm thick, fully inspectable in fluorescence, manufactured on Thermanox culture slides already used in bioreactors tested onboard the International Space Station. Using these scaffolds, we will set-up a cell model of glioblastoma multiforme. If successful, the relevant technology developments will bring the NICHOID up to prototype level with potential customer interests in using this advanced substrate in multiple applications of biological research in space.