The National Heart, Lung and Blood Institute, part of the National Institutes of Health, has granted $920,000 to a team of researchers at the University at Buffalo (UB) to develop a model that mimics human lung tissue. The researchers say their model should offer an accurate and rapid way to test treatment candidates for pulmonary fibrosis (PF).
PF is a progressive lung disease characterized by the thickening and stiffening of lung tissue, leading to permanent scarring (fibrosis) that gradually compromises a person’s ability to breathe. Since lung scarring cannot be healed, current treatments focus on managing symptoms and treating the underlying causes of the disease, if known.
But to date, the majority of medications designed to treat PF have failed clinical trials, the researchers said.
“The main obstacles to the development of anti-pulmonary fibrosis drugs are the slow progression of the disease and the high cost and large sample size needed for animal studies and clinical trials,” Ruogang Zhao, PhD, associate professor in UB’s department of biomedical engineering and lead principal investigator, said in a university press release.
Due to the high costs of such clinical trials, screening assessments in the lab are needed to collect early evidence of the effectiveness of potential therapies. However, there is a lack of good lab models that capture disease features, like the scarring and tissue stiffening that occur over time in PF.
To address these issues, Zhao and co-investigator Yun Wu, PhD, also an associate professor in biomedical engineering, have launched a two-year project to develop a new preclinical model to study the mechanisms of fibrosis progression. Zhao and Wu will use the model to evaluate the efficacy of potential therapies in vitro (in the lab).
“We hope that our work will expedite the translation of drug candidates from the laboratory to clinics, and that this technological advancement will positively impact current practice to combat fibrotic diseases,” Zhao said.
The team is using biofabrication technologies to engineer a 3D microtissue array system that mimics, to some extent, the complex structure and composition of human lung tissues. Many of the 3D patterns, called microtissues, that the team is creating are about the same diameter as a single human hair.
The scientists are using one technique to print arrays of tiny squares, with micropillars of such thinness placed around the edges of each square. This approach replicates the thin morphology of the alveoli (the air sacs in the lungs) and enables the stretching of lung tissue over the micropillars.
The model will be used to study the mechanisms of inflammation-induced fibrosis and detect changes in tissue stiffness. These are closely related to scarring progression or reversal when treated with medications, the researchers said.
“Ruogang’s research is an excellent example of how biomedical engineering directly impacts the lives of many people,” said Albert Titus, PhD, professor and chair of the department of biomedical engineering.
“He and Yun are developing new knowledge and tools that can improve drug development and ultimately lower costs,” Titus said, adding, “This is really exciting work.”
Zhao noted that his work also may help advance treatments for related diseases, including COVID-19.
“It is possible that this research can help discover treatments for people infected with the disease and contribute to the battle against the pandemic,” Zhao said.
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