Download Cyclically stretched 3D bioprinted bioartificial alveolar sacs

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],