# A Hydrogel-Based Cellular Model of the Human Vocal Fold

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2023 · $496,738

## Abstract

Project Summary
 Voice is produced when the vocal folds are driven into a wave-like motion by the airstream from the trachea,
converting aerodynamic energy and airflow into acoustic energy in the form of sound. Each vocal fold consists
of a pliable vibratory layer of connective tissue, known as the lamina propria (LP), sandwiched between a muscle
and a stratified squamous epithelium (EP). Numerous environmental, mechanical and pathological factors can
damage this delicate tissue, resulting in vocal fold scarring that affects millions of Americans with limited
treatment options. Although there is a general consensus on the pathophysiology of vocal fold scarring, the
molecular and cellular mechanisms that control unremitting fibrosis remain poorly understood. Studies on other
fibrotic diseases suggest that fibroblasts, epithelial cells and the interstitial matrix are active players in
fibrogenesis. This project aims to engineer a reliable, physiologically relevant in vitro tissue model that can be
used to investigate vocal fold development, health, and disease, and more importantly, to facilitate the
development and testing of new treatment options. We propose to develop a microengineered organ chip that
integrates the epithelial and mesenchymal cells in a tissue-mimetic configuration with built-in airflow to stimulate
phonation. Using the microfluidic model, we will investigate how damage to the epithelium initiates fibrosis, how
the fibrotic extracellular matrix (ECM) sustains fibrosis and how myofibroblast proliferation and matrix deposition
continue unabated. Finally, we will calibrate our model with an antifibrotic growth factor that has shown efficacy
in treating vocal fold scarring, and test a promising pharmacological inhibitor that has not been previously tested
in the context of vocal fold scarring. Highly efficient bioorthogonal tetrazine ligation will be used to establish the
initial LP matrix surrounding healthy fibroblasts and to introduce compositional and mechanical alterations that
promote fibroblast activation. Pluripotent and multipotent stem cells will be guided to differentiate into vocal fold-
like epithelial cells and fibroblasts by adopting a development paradigm and through systematic manipulation of
the engineered microenvironment. Piezoresistive strain sensors embedded in the sidewalls of the microfluidic
channels will be used to monitor tissue stiffness and EP permeability in situ. The microengineered tissue model
will be characterized in terms of cell phenotype, microstructure, mechanical properties and physiological function.
For comparison purposes, a stand-alone, human-sized vocal fold model will be developed and characterized
employing methodologies established in the laryngology field. Data generated from this project should
significantly impact fundamental research related to vocal fold scarring and provide critical information on
therapeutic decision-making in the near future.

## Key facts

- **NIH application ID:** 10604269
- **Project number:** 5R01DC014461-08
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Xinqiao Jia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $496,738
- **Award type:** 5
- **Project period:** 2015-12-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604269

## Citation

> US National Institutes of Health, RePORTER application 10604269, A Hydrogel-Based Cellular Model of the Human Vocal Fold (5R01DC014461-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10604269. Licensed CC0.

---

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