# Tissue-engineered trachea composites for long-segment airway replacement (DIVERSITY SUPP - Hussein)

> **NIH NIH R01** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2024 · $85,869

## Abstract

PROJECT SUMMARY
 Pediatric long-segment airway defects are caused by congenital malformations or result from trauma,
infection, or malignancy. Although rare, these defects are often fatal. There is currently no established surgical
technique to repair long-segment tracheal defects and the reconstructive options remain heroic. Tissue
engineering has the potential to replace failed tissue with a normal, living organ. Despite its potential, clinical
outcomes of tissue engineered tracheal grafts (TETG) have been poor.
 The main barriers to translation of tracheal replacement are graft collapse and delayed epithelialization.
We assessed the performance of partially decellularized tracheal grafts (PDTG) in our mouse model of orthotopic
tracheal replacement. Using resorbable biomaterials to stabilize PDTG, we created a Composite Tracheal Graft
(CTG). We hypothesize the CTG can improve overall survival in long-segment tracheal replacement, attenuate
graft collapse, promote extracellular matrix (ECM) production and SAE differentiation.
 To test this hypothesis, we will first assess how CTG promotes ECM regeneration in the tracheal
cartilage. In our first aim, we will implant PDTG and CTG in a mouse model of tracheal replacement and quantify
ECM production and mechanical properties. Using a conditional knock-out of chondrocyte-mediated ECM
production, we will then assess the impact on graft chondrocytes on ECM production. In our second aim, we will
define how SAE differentiation is promoted by CTG. We hypothesize that modification of graft dimensions with
splinting reduces wall shear stress (WSS) resulting in improved epithelial differentiation. To test the effect of
WSS on SAE differentiation, we will implant PDTG and CTG of normal and small diameter, thus increasing WSS
by reducing graft radius. To quantify WSS, we will use computational fluid dynamics (CFD) to topographically
map WSS through the grafts and correlate these values with quantitative immunofluorescenceof neo-epithelium.
Finally, we will validate CTG performance in an ovine model of tracheal replacement in our third aim. Using
routine radiographic and endoscopic surveillance, we will quantify animal survival, clinical manifestations, graft
dimensions, and graft regeneration.
 This proposal advances the field of airway tissue engineering through the development of a composite
tissue engineered tracheal graft and defining the mechanical factors contributing to graft regeneration.

## Key facts

- **NIH application ID:** 10938480
- **Project number:** 3R01HL157039-04S1
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Tendy Chiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $85,869
- **Award type:** 3
- **Project period:** 2021-07-16 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938480

## Citation

> US National Institutes of Health, RePORTER application 10938480, Tissue-engineered trachea composites for long-segment airway replacement (DIVERSITY SUPP - Hussein) (3R01HL157039-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10938480. Licensed CC0.

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