# Engineering a Self-assembled, multi-tissue Tracheal Replacement

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $465,966

## Abstract

Abstract
There is currently no successful treatment for long-segment tracheal stenosis, most commonly a result of
prolonged intubation or tracheostomy. Available treatment options are inadequate in preventing restenosis
and often require successive surgeries. A tissue engineered trachea has the potential to fill this need. A
functional tracheal replacement must (1) have radial rigidity, (2) be vascularized or encourage
vascularization and (3) contain respiratory epithelium to restore an open airway while avoiding restenosis,
bacterial infections and ischemic necrosis. This proposal seeks to develop a tracheal replacement with
these functional requirements by fusing tissue rings into a composite tissue tube comprised of multiple cell
types with controlled, localized growth factor presentation, and to evaluate its ability to serve as a
tracheal replacement in a rabbit airway defect model in vivo. The hypothesis of this work is that a multi-
cell type, scaffold-free neotrachea can be engineered with vital cellular organization and critical
functionality by delivering bioactive factors in a spatiotemporally controlled manner to modular tissue units
comprised of self-assembled human cells. By utilizing a custom assembly system, we will integrate the
tissue ring units into a composite tubular tracheal construct. Specifically, the proposal aims to (1) engineer
cartilaginous ring and tubular structures with defined dimensions and requisite mechanical properties using
high-density hMSC culture to serve as radial support in the neotrachea, (2) engineer cartilage-prevascular
composite tubular constructs with alternating cartilage and vascular tissue rings to support blood vessel
formation in the neotrachea, (3) engineer a luminal epithelial lining on cartilaginous tubes for interfacing
with the external environment and (4) test the capacity of the engineered tracheas to restore airway
functionality in an animal defect model. This work seeks to engineer a replacement human trachea with
radial rigidity that supports vascularization and epithelialization when implanted in vivo. This bottom-up, self-
assembled high-cell density strategy with localized bioactive factor presentation is a novel, modular approach
to engineer a multi-tissue, function-restoring organ of the respiratory system for patients suffering from
large and currently untreatable tracheal defects. This platform technology also has the potential to be
employed to regenerate other complex tissues and organs in the body.

## Key facts

- **NIH application ID:** 9923657
- **Project number:** 5R01EB023907-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Eben Alsberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $465,966
- **Award type:** 5
- **Project period:** 2019-03-22 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923657

## Citation

> US National Institutes of Health, RePORTER application 9923657, Engineering a Self-assembled, multi-tissue Tracheal Replacement (5R01EB023907-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9923657. Licensed CC0.

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