Project Objectives
- Build a human‑cell‑based Idiopathic pulmonary fibrosis (IPF)‑on-chip model that mimics the stages of lung fibrosis.
- Reproduce key biophysical features of IPF, including tissue stiffness, repetitive micro‑injury, and fibroblast activation.
- Develop measurable read‑outs that capture how fibrosis progresses and how cells respond to treatment.
- Test approved and failed anti‑fibrotic drugs to evaluate whether the chip model predicts human outcomes more accurately than animal models.
3Rs Impact
- Replaces the bleomycin rodent model with a fully human, chip‑based system for studying lung fibrosis.
- Reduces the need for hundreds to thousands of rodents used annually in academic and industrial IPF research.
- Provides more clinically relevant data, decreasing the number of ineffective drugs advanced into animal studies.
- Offers a platform that can be adapted to other fibrotic diseases, broadening long‑term replacement potential.
Background
Idiopathic pulmonary fibrosis (IPF) is a severe, progressive lung disease with limited treatment options. The most widely used preclinical model is the bleomycin‑induced lung injury model in rodents. Although this model is considered the gold standard, it poorly predicts clinical outcomes in humans. Many drugs that appear effective in bleomycin‑treated mice fail in clinical trials, largely due to biological differences between the species and the mismatch between acute bleomycin injury and the slow, irreversible nature of human IPF.
To address this gap, the research team has developed a second‑generation lung‑on‑chip platform featuring a stretchable collagen‑elastin membrane that can mimic the mechanical environment of the human lung. By using primary human alveolar epithelial cells and fibroblasts from IPF patients, the project aims to create a physiologically relevant IPF‑on‑chip model. This system will allow researchers to study how fibrosis develops under realistic mechanical and biochemical conditions, and to test anti‑fibrotic drugs in a human‑based environment.
A validated IPF‑on‑chip model could provide a far more predictive alternative to animal testing, improving drug development efficiency and reducing reliance on rodent models that cause significant distress.
