Mapeando o potencial de plataformas breast-on-a-chip para radioterapia personalizada

This proposal aims to go beyond the current state-of-the-art, by addressing one of the main challenges in the medicine field and cancer research: tools that allow mimic closer clinical patient-centred treatments. At its core, this project clearly addresses these challenges, as advanced 3D biomimetic in vitro cell culture microfluidic platforms are proposed for effective radiobiology research, in which non-neoplastic and neoplastic cells can be cultured in a microenvironment that simulate the in vivo niche. This is a novel strategy based on dynamic culture and functionalized perfusable scaffolds that will make this combined system unique for the study of cancer physiopathology under RT (Annex II). This concept arises from the need to deeper understand the correlations between therapeutic radiation dose and biological damage in realistic microenvironments and ultimately validate the platform using human tissues from cancer patients with the long-term objective to support the design of non-invasive personalized cancer treatments. The proposed methodology will be applied to breast cancer as the model disease for its relevance in medicine, with well-documented clinical data, allowing the proper validation of the solutions generated. The research strategy will be designed to pursue the following intermediate targets: -Development of 3D cell culture microenvironments consisting of perfusable scaffolds with tailored architecture and stiffness and coated with physiologically relevant ECM biomolecules; -Identification of optimal scaffold physicochemical properties, including functional coating, able to improve viability, proliferation, and phenotype maintenance of breast cells in vitro and identification of secreted growth factors-GF and cytokines-Cyt; -Development of dynamic in vitro breast-on-a-chip platforms integrating a thermocouple and a wireless module to monitor in real-time the temperature throughout platform handling, cell culture and irradiation assays; -Evaluation of the predictive capacity of the optimized 3D breast-on-a-chip microenviroment. The effect of RT on non-neoplastic and neoplastic breast cells, and ultimately on breast tissues, will be evaluated by comparing the response with that obtained in conventional 2D culture platforms and expected in vivo. For the best of our knowledge, this is a pioneering project with high potential for excellence science and technology transfer, since studies that investigate in vitro the impact of RT are still very scarce, justifying the timeless of the proposed work. The produced solutions and platforms have the potential to be extrapolated to other cancers and may additionally be used to assess anti-cancer drugs and the combined effects of RT and CT. Radio4Breast will be leaded by a full-time Assistant Researcher, VFCardoso, supported by other researchers and medical physicist from UMinho and IPO-Porto with complementary areas of expertise that will guarantee the scientific environment and infrastructures for the proper development of this ambitious project. Further, the project is based on in/dependently developed and proven technologies by the members of the team (Annex III for representative past and on-going research of the research team aligned with the proposal and references [TM]). Thus, the present project will develop a novel biomedical tool with a TRL7, allowing further progress towards commercialization and widespread use.