New Lung-on-a-chip Technology Captures Fibrosis Progression and May Speed Treatment Discovery, Study Reports

New Lung-on-a-chip Technology Captures Fibrosis Progression and May Speed Treatment Discovery, Study Reports

A new lung-on-a-chip technology models the mechanical changes that occur in the lungs during idiopathic pulmonary fibrosis, possibly allowing for a faster and less expensive screening of potential new anti-fibrotic therapies, a study reports.

“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,” Ruogang Zhao, PhD, the study’s lead author and an assistant professor at the University at Buffalo, said in a university news article by Cory Nealon.

The study, “Fibrotic microtissue array to predict anti-fibrosis drug efficacy,” was published in the journal Nature Communications.

A major drawback in the development of therapies for pulmonary fibrosis is the lack of good in vitro models that capture disease features, like the scarring and tissue stiffening that occurs over time.

As a result, only two therapies – Esbriet (pirfenidone) and Ofev (nintedanib) — working to slow lung fibrosis have been approved by the U.S. Food and Drug Administration (FDA). Both therapies are only suitable for one type of such fibrosis — idiopathic pulmonary fibrosis – leaving all the other types, more than 200 of them, without effective treatments.

Researchers with the university’s Department of Biomedical Engineering created a lung-on-a-chip to model the changes that occur in lungs during fibrosis progression.

They used a technique called microlithography – used to print electronic chips – to first build micro silicon-based pillars. They then placed mixtures of human lung small airway epithelial cells or lung fibroblasts over these micropillars. The cells began to spread and ultimately arranged in structures that mimic the lungs’ alveoli, the tiny air sacs that allow us to consume oxygen.

To test the research potential of this lung-on-chip technology, the team added the pro-fibrotic factor TGF-beta to their system. They saw that treatment with TGF-beta for six days induced fibrosis.

The researchers then tested the potential of this model system to study the efficacy of anti-fibrosis treatments, using Esbriet and Ofev. Results showed that, although the therapies have different degrees of inhibition of fibrosis, both can effectively prevent tissue stiffening.

Overall, these findings support the potential of this new system to help predict the efficacy of anti-fibrosis therapies — and potentially a better understanding of how Esbriet and Ofev work inside a person’s lungs.

“This finding started to unveil the potential biomechanical mechanism of action of pirfenidone [Esbriet] and nintedanib [Ofev] on fibrosis treatment,” the researchers wrote.

“It is expected that the multiscale and pathophysiologically relevant modeling capability of the fibrotic microtissue system will expedite the translation of anti-fibrotic therapies from the laboratories to the clinics,” they concluded.

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