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Title : Introduction : Research work: Cyclically stretched 3D bioprinted bioartificial alveolar sacs In the quest to develop in-vitro models that best predict the drug response in humans, organs-on-chip is a new technology that is expected to revolutionize the way drug discovery process is carried out. The human lung parenchyma with its complex and dynamic (respiration) architecture is unique and particularly challenging to mimic. Available in-vitro models of the lung only poorly mimic the air-blood barrier and its particular environment. Recently in-vitro models able to reproduce the thin alveolar barrier as well as the mechanical stress induced by the respiration have been reported, also by our group (Stucki 2015). Although such lung-on-chip systems represent an important advance in the field, they are made of polymeric material on which cells are cultured. Unfortunately, these materials importantly affect the phenotype of the cells and do not by far represent the in-vivo cellular environment of the lung parenchyma. In this project, we aim at creating lung alveoli in-vitro with an in-vivo resemblance never reached before. 3D bioprinting technology, organs-on-chip technology and cell culture techniques will be combined to create ultrathin basal membrane made of collagen and elastin, on which human lung epithelial cells and endothelial cells will be cultured. Further, we planned to cyclically stretch the collagen-elastin membrane in three dimensions to reproduce the respiration movements. The main techniques learned will be: biological experiences: - aseptic cell culture techniques - advanced organotypic models - immunocytochemistry (ICC) - confocal microscopy - ev. ELISA and micro-PCR - functional assays (viability, mechanical stiffness) - ev. use of patient-derived primary cells microfabrication: - 3D bioprinting - soft-lithography - organs-on-chip fabrication Relevance: The ultimate aim of this project is to create a model that closely mimics the complex cellular architecture of the lung parenchyma, including type I (in orange in the picture) and type II (in red in the picture) that are responsible for the surfactant production. References: 1. Logan, C. Y. and Desai, T. J. (2015), Keeping it together: Pulmonary alveoli are maintained by a hierarchy of cellular programs. Bioessays, 37: 1028–1037. doi: 10.1002/bies.201500031 2. Stucki AO, J. D. Stucki, S. Hall, M. Felder, Y. Mermoud, R. Schmid, T. Geiser, and O. T. Guenat, Lab Chip, 2015, 15, 1302–1310. PMID: 25521475. Student: Strong interests in interdisciplinary (cell culture with new technologies) and demanding project. The proposed project does NOT include animal experimentations. Date of start: Location: Upon mutual agreement The MSc project will be performed at the ARTORG Organs-on-Chip Technologies Lab, Murtenstrasse 50, 3008 Bern. Supervisor: Prof. Dr. Olivier Guenat, ARTORG Organs-on-Chip Technologies Lab, Bern [email protected] , 031 632 7608 Co- supervisor: Janick Stucki, ARTORG Center, Organs-on-Chip Technologies, Bern [email protected],