# An inflammation-induced fibrosis-on-chip system for the testing of anti-fibrosis drugs

> **NIH NIH R33** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $452,381

## Abstract

Idiopathic pulmonary fibrosis (IPF), characterized by the progressive stiffening of lung tissues, is a severe
disease with no cure. The understanding of the IPF pathogenesis is incomplete, but inflammation has been
identified as one of the major mediators and has been proposed as a therapeutic target for the development of
anti-IPF drugs. However, since existing in vitro fibrosis models are composed of limited cell types and utilize
rigid 2D culture formats, they cannot recapitulate the interaction between multiple profibrotic cells (macrophage,
myofibroblast) and the physiological stresses (shear flow, matrix stiffening, tissue contraction) in the fibrotic
tissue. As a result, these models are not able to provide the efficacy readout on the “therapeutic targets” of the
anti-fibrosis drugs. The objective of this renewal project is to develop a co-cultured fibrotic microtissue system
that can model the fibrogenesis event caused by the inflammation and predict the therapeutic efficacy of the
anti-fibrotic drugs that target inflammation pathways. Investigators have previously developed a static, mono-
cultured fibrotic microtissue system that can recapitulate the late-stage fibrogenic changes in tissue
biomechanics and histology caused by myofibroblast differentiation. However, this system is limited in
predicting the efficacy of drugs that target important early stage fibrogenesis events. In the current project,
investigators propose to expand the fibrosis modeling capacity of the existing system by including early-stage
fibrogenesis events, such as flow-mediated profibrotic activation of the macrophages and inflammation induced
myofibroblast differentiation. With this improved modeling capability, the new system will allow the examination
of the drug efficacy on the inflammatory pathways, thus validating the mechanism of action of the drug on the
intended target. The aims will include to develop a co-cultured fibrotic microtissue system that can model
inflammation-induced fibrogenesis of the lung interstitial tissue and to evaluate the screening capacity of the
microtissue system for anti-fibrosis drugs that target the inflammatory pathway. It is expected that such a
system will be able to simulate the therapeutic effects of the drug candidates on inflammatory pathways, thus
allowing the delineation of the therapeutic mechanism of the drug. Such a new approach can significantly
expedite the translation of anti-fibrotic therapies from the laboratories to the clinics.
1

## Key facts

- **NIH application ID:** 10241534
- **Project number:** 5R33HL154117-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Ruogang Zhao
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $452,381
- **Award type:** 5
- **Project period:** 2020-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241534

## Citation

> US National Institutes of Health, RePORTER application 10241534, An inflammation-induced fibrosis-on-chip system for the testing of anti-fibrosis drugs (5R33HL154117-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241534. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*