# Engineering 3D microtissues of pulmonary fibrosis.

> **NIH NIH F31** · GEORGIA INSTITUTE OF TECHNOLOGY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Idiopathic pulmonary fibrosis (IPF) is a chronic age-associated disease with a median survival of 3-5 years
following diagnosis. Current antifibrotic treatments, pirfenidone and nintedanib, slow the progression of IPF but
are insufficient in halting or reversing this disease. While the etiology remains unknown, fibroblast-mediated
extracellular matrix (ECM) remodeling leading to the development of fibroblastic foci appears to be a critical
component of IPF. The objective of this project is to engineer an in vitro 3D pulmonary microtissue model
to explore the contribution of age-associated pathways to fibroblast-mediated ECM remodeling. My
previous work generating microtissues supports the feasibility of developing this in vitro 3D pulmonary
microtissue model. Additionally, microtissues have been previously used to study cell-matrix interactions
including in the context of fibrosis. A main advantage of using the microtissues system to study fibrotic diseases
is the ability to assess real-time changes in contractility and cell migration in a medium throughput system. My
central hypothesis is that senescence-associated secretory phenotype (SASP) and the development of
an apoptosis-resistant phenotype in senescent fibroblasts contribute to ECM remodeling in IPF. The
overall objective and hypothesis will be accomplished across three specific aims: 1) Engineer pulmonary
microtissues using human fibroblasts isolated from IPF and healthy tissues of various ages; 2) Evaluate the
senescence-associated secretory phenotype of IPF fibroblasts and determine its effects on microtissue
remodeling; and 3) Assess the development of an apoptosis-resistant phenotype in senescent cells and evaluate
the role of FAK in regulating apoptosis. Expected outcomes for this project include: 1) An in vitro pulmonary
microtissue model capable of detecting differences in microtissue contractility, stiffness, cell migration, and ECM
remodeling; 2) Determining the impacts of SASP on ECM remodeling and evaluating the therapeutic benefit of
targeting specific components of SASP; and 3) Assessing FAK’s role in preventing apoptosis in senescent cells
and evaluate the therapeutic benefit of FAK inhibition. The results of this study will elucidate the role of
fibroblast senescence in the development and progression of pulmonary fibrosis and identify potential
druggable targets.

## Key facts

- **NIH application ID:** 10901715
- **Project number:** 1F31HL174133-01
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** ELISA B NIEVES
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-08-19 → 2025-08-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901715

## Citation

> US National Institutes of Health, RePORTER application 10901715, Engineering 3D microtissues of pulmonary fibrosis. (1F31HL174133-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10901715. Licensed CC0.

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