Modelo in vitro de intestino num dispositivo microfluídico biofabricado para entender as interações tecido-microbiota

An unbalanced constitution of the gut microbiota is associated with various diseases as colorectal cancer (CRC), representing one of the more considerable burdens for the patients and healthcare systems. In fact, intestinal microbiota can interact with colonic epithelia and immune cells through the release of different metabolites, proteins, and macromolecules, triggering the development of CRC. Different strategies, from 2D (transwells) to 3D (scaffolds and organoids) setups, have been pursued to model intestinal tissue. But none have successfully capable to mimic such intricate environment. In this reasoning, organ-on-chip approaches have sparkled the field by mimicking the native microenvironment and physiological conditions more accurately. Also, they provide a platform for testing the effects of drugs in a more controlled and representative manner, and can be interconnected to simulate the interactions between different organs. Yet, they lack morphological cues that can support and guide cell growth. To overcome this limitation, the Glance project envision to create a 3D in vitro model using 3D printing to mimic the complex intestinal crypt-villi architecture within a perfusion microfluidic device, and then colonize it with relevant cells. The MAIN SCIENTIFIC OBJECTIVES of Glance project is the creation of a robust setup comprising an intestine-on-chip connected to a CRC-on-chip proficient in mimicking in vivo responses of human intestinal epithelial cells and cancer cells when exposed to gastrointestinal microbiota. Envisioning in the future bring to light improved therapeutic strategies. To achieve such milestone, the project is divided into four objectives: 1) the development of a hydrogel-based ink to biofabricate villi-crypt model that better emulates mechanical properties of intestinal tissue and improves cell’s attachment, growth and proliferation; 2) the optimization of printing conditions and print villi-crypt structures within a microfluidic device; 3) the production of intestine-on-chip and CRC-on-chip by culture epithelial/fibroblasts cells, and in the cancer model culture CRC cells, under constant flow and stretch conditions; 4) the successful connection of the two models (healthy and CRC environment), and 5) the testing of the effect of intestinal microbiota on the connected models. Envisioning in the future bring to light improved therapeutic strategies. Furthermore, OTHER OBJECTIVES of Glance are 1) the establishment of an innovative research line and consequently, open new positions, improving the scientific employment and contributing to applicant’s career, namely for her independent establishment, 2) the spreading of obtained results on leading international journals and conferences held nationally and internationally, and 3) the dissemination of knowledge to other interested parties (e.g. patients, group associations, possible investors within the industrial community).