Lung-on-a-chip simulates pulmonary fibrosis

May 25, 2018 by Cory Nealon, University at Buffalo
The image above shows collagen from a healthy engineered lung tissue. Credit: Ruogang Zhao

Developing new medicines to treat pulmonary fibrosis, one of the most common and serious forms of lung disease, is not easy.

One reason: it's difficult to mimic how the disease damages and scars lung over time, often forcing scientists to employ a hodgepodge of time-consuming and costly techniques to assess the effectiveness of potential treatments.

Now, new biotechnology reported in the journal Nature Communications could streamline the drug-testing process.

The innovation relies on the same technology used to print electronic chips, photolithography. Only instead of semiconducting materials, researchers placed upon the chip arrays of thin, pliable lab-grown lung tissues—in other words, its lung-on-a-chip technology.

"Obviously it's not an entire lung, but the technology can mimic the damaging effects of . Ultimately, it could change how we test new drugs, making the process quicker and less expensive," says lead author Ruogang Zhao, PhD, assistant professor in the Department of Biomedical Engineering at the University at Buffalo.

The department is a multidisciplinary unit formed by UB's School of Engineering and Applied Sciences and the Jacobs School of Medicine and Biomedical Sciences at UB.

The image above shows the nucleus from a healthy engineered lung tissue. Credit: Ruogang Zhao

With limited tools for study, scientists have struggled to develop medicine to treat the disease. To date, there are only two drugs—pirfenidone and nintedanib—approved by the U.S. Food and Drug Administrations that help slow its progress.

However, both drugs treat only one type of lung fibrosis: idiopathic . There are more than 200 types of lung fibrosis, according to the American Lung Association, and fibrosis also can affect other vital organs, such as the heart, liver and kidney.

Furthermore, the existing tools do not simulate the progression of lung fibrosis over time—a drawback that has made the development of medicine challenging and relatively expensive. Zhao's research team, which included past and present students, as well as a University of Toronto collaborator, created the lung-on-a-chip technology to help address these issues.

Using microlithography, the researchers printed tiny, flexible pillars made of a silicon-based organic polymer. They then placed the tissue, which acts like alveoli (the tiny air sacs in the lungs that allow us to consume oxygen), on top of the pillars.

The image above shows actin from a healthy engineered lung tissue. Credit: Ruogang Zhao

Researchers induced fibrosis by introducing a protein that causes healthy lung cells to become diseased, leading to the contraction and stiffening of the engineered lung tissue. This mimics the scarring of the lung alveolar tissue in people who suffer from the disease.

The tissue contraction causes the flexible pillars to bend, allowing researchers to calculate the tissue contraction force based on simple mechanical principles.

Researchers tested the system's effectiveness with pirfenidone and nintedanib. While each drug works differently, the system showed the positive results for both, suggesting the lung-on-a-chip technology could be used to test a variety of potential treatments for fibrosis.

Explore further: Restoring lipid synthesis could reduce lung fibrosis

More information: Mohammadnabi Asmani et al. Fibrotic microtissue array to predict anti-fibrosis drug efficacy, Nature Communications (2018). DOI: 10.1038/s41467-018-04336-z

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Anonym458465
not rated yet May 27, 2018
A CT scan in August of 2009 verified that I had Idiopathic Pulmonary Fibrosis. My first symptoms were cough and shortness of breath. I was on prednisone and inhalers. My blood oxygen level was 50 and i was extremely short of breath, i was barely able to breath. I went through cardio pulmonary rehab, It helped but not too long before all the severe symptoms returned. December last year, a family friend told us about Rich Herbs Foundation and their successful lungs disease treatments, we visited their website ww w. richherbsfoundation. c om and ordered their IPF herbal treatment, i am happy to report this treatment effectively reversed my Idiopathic pulmonary fibrosis and symptoms. I am back on my feet, i walk daily now and has made me able to walk my two dogs again without shortness of breath or sudden loss of energy. My activity level is up again.

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