3D engineered brain cancer micro-environments

Principal Investigator: dr. Angelo Accardo (TU Delft)

PhD student: Quais Akolawala (TU Delft)

Funding: NWO-XS 2021

Description

Glioblastoma is a brain tumour and the most aggressive cancer type. The incidence is about 2-3 cases per 100.000 people per year. These patients have a poor prognosis, about 15-17 months after diagnosis, even after resection of the tumour followed by radiotherapy (also known as x-ray therapy) and adjuvant temozolomide. Compared to X-ray radiotherapy, Proton Beam Therapy is able to release energy more precisely to the tumour, especially thanks to the recent introduction of commercial pencil-beam scanning systems, with less scattering to surrounding tissues. In such context however, it is still controversial the role of proton irradiation on some specific cancer cells and its effect on healthy cells. One of the main reasons is the lack of a systematic study on the morphological and functional changes of the cells after being exposed, which cannot be routinely performed on patients or living tissues coming from biopsies. To fill this gap, we propose the creation of standardized, reproducible and physiologically relevant 3D engineered cell microenvironments (Onco-Neuro-Scaffolds, ONSs) to be used as a benchmark tool for proton Radiobiology.

To our knowledge, there is no reported literature on the use of 3D nanostructured cell microenvironments for in-vitro testing of proton radiotherapy effects. Recently, we created laser-assisted additive manufactured (AF) 3D microenvironments that allowed the development of 3D neuroblastoma cell networks. Also, we characterized both the cellular morphological and functional immunofluorescent features by employing a multi-technique imaging protocol involving scanning electron microscopy (SEM) and two-photon confocal imaging (2PI). To achieve the goal of this project, we propose to exploit two-photon polymerization (2PP) and stereolithography (SLA) fabrication strategies for the realization of ONSs fostering the formation of 3D biomimetic networks and pseudo-tissue structures (i.e. spheroids) of both neural healthy cells and glioblastoma ones mimicking the features of the natural tissue. The ONSs will be then employed for systematically characterizing the effect of proton radiation doses on cellular behaviour (e.g. proliferation, migration), morphology and viability by using SEM and 2PI. The obtained results will pave the way for pre-treatment characterization and response assessment of tumour and healthy tissues.