Lung-on-a-Chip Technology Simulates Pulmonary Fibrosis

The innovation relies on photolithography, the same technology used to print electronic chips. However, instead of semiconducting materials, researchers placed upon the chip arrays of thin, pliable lab-grown lung tissues.

In other words, it’s lung-on-a-chip technology.

“Obviously it’s not an entire lung, but the technology can mimic the damaging effects of lung fibrosis. Ultimately, it could change how we test new drugs, making the process quicker and less expensive,” says Zhao, lead author on the study, titled “Fibrotic Microtissue Array to Predict Anti-Fibrosis Drug Efficacy,” which was reported May 25 in the journal Nature Communications.

Developing new medicines to treat pulmonary fibrosis — one of the most common and serious forms of lung disease — is not easy. That’s because it has been difficult to mimic how the disease damages and scars lung tissue over time, often forcing scientists to employ a hodgepodge of time-consuming and costly techniques to assess the effectiveness of potential treatments.

With limited tools for fibrosis 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 Administration that help slow its progress.

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

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 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.

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 lung fibrosis.

Two current students in Zhao’s lab and four of his former students worked on the project while pursuing degrees in biomedical engineering and are co-authors.

Mohammadnabi Asmani and Zhaowei Chen are working in the lab while pursuing doctoral degrees. Sanjani Velumani, Yan Li and Isaac Hsai all worked in the lab while earning master’s degrees. Nicole Wawrzyniak worked in the lab while getting her bachelor’s degree.

Boris Hinz, PhD, University of Toronto Distinguished Professor of tissue repair and regeneration, is also a co-author.

In addition to the Jacobs School of Medicine and Biomedical Sciences, additional research support was provided by the National Institutes of Health, the UB School of Engineering and Applied Sciences and UB’s Clinical and Translational Science Institute.