Easy-on-a-chip v.2.0
A team of researchers from the University Clinic of Bern and the ARTORG Biomedical Research Center of the University of Bern has developed an advanced model of a lung on a chip consisting of life-size alveoli located on a stretchable membrane made of completely biological material. The new model reproduces key aspects of the architecture of lung tissue that were absent in previous versions. Thanks to it, new fundamental research will be possible to understand various lung pathologies, drug screening and precision medicine.
The lung is a paired organ, the main function of which is gas exchange. Due to its complex structure, heterogeneous cellular composition and changing microenvironment, it is difficult to model it in vitro.
The specialized laboratory of the ARTORG Biomedical Engineering Research Center at the University of Bern, headed by Olivier Gena, has been creating in vitro models called "organs on a chip" for more than 10 years, focusing on modeling the lungs and their diseases. After the first successful lung-on-a-chip system demonstrating the main characteristics of the lungs, the Organs-on-Chip (OOC) Technologies laboratory in collaboration with the Helmholtz Center for Infectious Diseases Research and the Department of Thoracic Surgery and Pneumology of the University Clinic has developed a new generation lung-on-a-chip model.
Fully biodegradable hemato-air barrier in full size
The new lung-on-a-chip contains an array of alveoli with dimensions similar to alveoli in vivo. They lie on a thin stretchable membrane consisting of collagen and elastin, which are also found in human lungs. The membrane is stable, it can be cultivated on both sides for several weeks, it is biodegradable, and elastic properties allow you to simulate respiratory movements with mechanical stretching of cells.
Unlike the first–generation model, which was also created by the Olivier Gene group, the improved system reproduces key aspects of the extracellular matrix of the lungs: composition (the basement membrane consists of extracellular matrix proteins), structure (an array of alveoli with a size similar to that in vivo, as well as fiber structure) and properties (biodegradability is an important aspect of modeling hemato-air barrier in lung diseases, such as idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease). In addition, the manufacturing process of the new model is not as complicated and cumbersome as that of the first-generation light on a chip.
Immuno-staining of patient cell cultures on a second-generation lung-on-chip. © Pauline Zamprogno, ARTORG Center for Biological Engineering Research.
Wide potential for clinical application
The cells that will be cultured on the new chip for research are currently obtained from cancer patients who underwent lung resection in the Department of thoracic surgery at the University Hospital of Bern. A lung model on a chip can be seeded with healthy and/or diseased lung alveolar cells. This will give doctors both a better understanding of lung physiology and a predictive tool for drug screening and possibly precision medicine.
The potential of the new model is wide: from fundamental scientific research of lung functions and pathologies to the identification of new pathways and more effective discovery of potential new treatment methods.
A powerful alternative to animal models
An additional plus is that the new lung-on-a-chip can reduce the need for pneumological studies in animal models. Many drugs under development, successfully tested in preclinical models on rodents, have proved ineffective when tested on humans due to differences between species and features of the manifestation of lung disease. Therefore, in the long term, this will lead to a reduction in the number of animal experiments and provide more patient-friendly drug screening systems with the ability to adapt models to specific patients by seeding organs on a chip with their own cells.
A new biological lung-on-a–chip will be refined by researchers from the OOC Technologies group to simulate idiopathic pulmonary fibrosis, a chronic disease that leads to progressive scarring of lung tissue.
Article by P.Zamprogno et al. Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane is published in the journal Communications Biology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Bern: Bernese researchers create sophisticated lung-on-chip.