# Modeling pulmonary fibrosis progression caused by differential mechanical stretch

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $387,869

## Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no cure. IPF development follows a
unique pattern with fibrosis starting at the lung periphery and progressing toward the lung center. Little is
known about the mechanism underlying the periphery-to-center progression of the disease. Recent studies
suggest that the higher level of parenchymal expansion (strain) in the lung periphery serve to amplify and
perpetuate the progression of fibrosis upon initial lung injury. Systematic inquiry of the spatiotemporal
progression of pulmonary fibrosis has been challenging and cost prohibitive, because (1) correlative data on
both lung pathology and lung mechanics are difficult to obtain due to the prolonged disease progression in
human; (2) the most commonly used mouse model of bleomycin-induced fibrosis spontaneously resolves and
therefore fails to fully reflect human fibrosis, and (3) current in vitro lung tissue models do not reproduce an in
vivo-like strain gradient and the complex biomechanics existing in the native alveolar structure. The objective
of this project is to understand the spatiotemporal relation between pulmonary fibrosis and mechanical stretch
in the lung and develop a stretched engineered lung slice (ELS) model to study the multiscale biomechanical
mechanism of differential stretch-induced spatial progression of pulmonary fibrosis. The main hypothesis is
that the high level mechanical stretch at the lung periphery amplifies the pro-fibrotic signaling in injured lung
cells, thus initiating fibrosis and perpetuating the periphery-to-center fibrosis progression in the lung. Recently,
investigator’s team have adopted decellularization technique to create ELSs that support the long term growth
of lung cells in structurally-persevered human lung scaffolds. To utilize the ELS in the study of the fibrosis
progression, investigators plan to adopt a multiscale biomimicry strategy where the integration of ELS with a
gradient stretching device allows macroscopic modelling of the differential strains existing at the lung periphery
and lung center, and the preserved structure in the ELS allows microscopic modelling of the mechanical signal
transduction and cellular injury existing at the single alveolus level. The aims include characterizing the
spatiotemporal evolution of pulmonary fibrosis and mechanical stretch in both human and rat fibrotic lung
samples, developing a differentially-stretched, ELS model to test how realistic strain gradients affect spatial
progression of fibrosis upon epithelial injury, and understanding the multiscale biomechanical mechanism of
stretch induced fibrosis initiation and progression. The combination of mechanical stretching and computational
modeling with the lung slice model will substantially improve the utility of this underutilized model for lung
disease research, thus greatly facilitating the research efforts in pulmonary fibrosis and improving the
understanding of a major disease mechanism t...

## Key facts

- **NIH application ID:** 10423645
- **Project number:** 1R01HL163428-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Ruogang Zhao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,869
- **Award type:** 1
- **Project period:** 2022-08-05 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10423645

## Citation

> US National Institutes of Health, RePORTER application 10423645, Modeling pulmonary fibrosis progression caused by differential mechanical stretch (1R01HL163428-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10423645. Licensed CC0.

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