# Microfluidic Tissue Engineering of Small Airway Injuries

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $705,868

## Abstract

Microfluidic Tissue Engineering of Small Airway Injuries
This project brings together microfluidic, computational, and animal model expertise to evaluate the relative roles
of solid- and fluid-mechanical stresses causing, or exacerbating, or predisposing injury of small airway epithelia.
This proposal focuses on small airways because they are implicated as the first level of damage in acute
respiratory distress syndrome (ARDS) (1, 2). These airways are subject to closure and reopening during the
ventilatory cycle, and can be injured from the associated mechanics called atelectrauma. Since these airways
are coated with a liquid lining, all closure and reopening involves the formation, propagation, and rupture of liquid
plugs. Our previous work (3, 4) showed that fluid/surface tension forces from propagating and, especially,
rupturing liquid plugs are a significant cause of lethal injury to airway epithelial cells cultured on microfluidic,
lung-on-chip platforms. Animal models have also shown that a higher surface tension due to reduction in
concentrations of pulmonary surfactants as the major cause of small airway atelectrauma (5), while plug ruptures
with acoustical signatures are particularly associated with airway injury (6). Here, we propose to determine the
mechanism of atelectrauma while separating out the contributions of elastic vs fluid/surface tension forces in
experiment and computations. We hypothesize that fluid/surface tension mechanical forces in atelectrauma are
a major contributor to ARDS. We will also test the role of atelectrauma in the exacerbation of additional insults
such as, bacterial infection and acid aspiration, which are direct risk factors for the development of ARDS.
Although low tidal volumes have been shown to reduce mortality in patients with ARDS, the benefits of the open
lung ventilation concept remain controversial. One of the major reasons for the variable results of open lung
ventilation stems from the lack of understanding of the best way to prevent atelectasis. Understanding the
mechanism of small airway atelectrauma is essential for developing successful therapeutic interventions in
ARDS. While our main goal is to clarify fundamental mechanisms underlying ARDS pathology, our findings have
significant clinical implications. We have the potential to clarify whether personalized, appropriate levels of PEEP
or recruitment maneuvers may prevent atelectrauma and thereby result in mitigation of lung injury in ARDS.
The aims are designed to answer key questions such as: What is the relative contribution of stretch versus fluid
mechanical stress in causing lung injury? How will combined insults of fluid mechanical stress together with acid
aspiration or bacterial insult exacerbate lung injury?

## Key facts

- **NIH application ID:** 9928984
- **Project number:** 5R01HL136141-04
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** JAMES Bernard GROTBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $705,868
- **Award type:** 5
- **Project period:** 2017-06-03 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928984

## Citation

> US National Institutes of Health, RePORTER application 9928984, Microfluidic Tissue Engineering of Small Airway Injuries (5R01HL136141-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9928984. Licensed CC0.

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