Patients suffering loss of the larynx?s vocal fold cover due to trauma or laryngeal cancer can suffer disabling voice difficulties, and treatment options are limited. An implantable vibrating replacement tissue would revolutionize the treatment of laryngeal disorders. The work described in this proposal optimizes a Cell-based Outer Vocal fold Replacement (COVR) developed by this laboratory, identifies its functions in an animal model, and defines its potential clinical applications. Adult human stem cells isolated from adipose tissue are cultured within fibrin hydrogel to produce a three-dimensional tissue substitute suitable for vocal fold implantation. Preliminary work has developed and implanted the COVR in rabbits, finding excellent vibrational function. This work plans the systematic study of critical questions remaining for vocal fold replacement. Host interactions with implanted cells and matrix will be defined. Influence of pre-existing scar environment and sex will be assessed. Extracellular matrix regeneration will be promoted and mechanical behavior quantified. Successful completion of the proposed research will advance a tissue-engineered vocal fold towards human translation. This work will define suitable clinical scenarios (existing scar versus fresh tissue resection), maximize tissue mimicry of normal vocal folds, and identify mechanisms by which the COVR improves vocal fold wound healing relative to controls. The animal studies in this proposal will provide necessary information to proceed with formal pre-clinical trials.

Public Health Relevance

Vocal folds, the vibrating parts of the human larynx that produce voice, are subject to a number of injuries including surgeries for laryngeal cancer or noncancerous masses, radiation therapy for other head and neck cancers, and chronic severe acid reflux. Once the vocal folds are scarred, little can be done to restore their vibration and treat the ensuing disabling voice difficulties. This project develops an implantable vibrating replacement tissue, aiming to restore voice for persons with hoarseness due to vocal fold scarring.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC016959-03
Application #
9982294
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Shekim, Lana O
Project Start
2018-08-01
Project End
2023-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095