(99b) Engineering the Vocal Cords

The sound of the human voice originates from the paired vocal cords in the larynx. Sound waves are generated when exhaled airflow from the lungs drives the cyclic collisions of the two vocal cords, hundreds of times per second. This oscillation is the fortunate outcome of tracheal pressure balanced with tissue elasticity, as air pressure fluctuations intermittently force opening and closing of the glottic valve. The vocal cord microstructure develops to permit and withstand this recurrent high-speed trauma from shear forces and impacts. Its layered structure and extracellular matrix (ECM) rich in elastic fibers and hyaluronic acid are unmatched by any other tissue.

Vocal cord injury disrupts this specialized ECM. As the structure stiffens, function follows form and the voice becomes harsh and effortful. Traditional repair efforts are disappointing, due to the ubiquitous challenges in remodeling scar tissue. Regenerative medicine and tissue engineering have been proposed as an alternative for these patients who suffer social isolation and occupational limitation due to their voice disability.

One investigational approach excises the vocal cord scar tissue and replaces it with a simple tissue-engineered structure of fibrin with adipose-derived multi-potent stromal cells. Tissue remodeling ensues, and the resulting vocal cords are able to vibrate for sound production in a rabbit model. Comparison with normal vocal cord transplantation shows superior function with the tissue-engineered structure. Results suggest that modulation of wound healing is required to preserve the complex ECM structure that permits vibratory function.

In this talk, the physiology and biomechanics of voice production will be reviewed. The unique vocal cord structure will be demonstrated in normal and diseased states. The status of cell-based therapies in the larynx will be reviewed, with special attention to the three-dimensional tissue-engineered implant developed in this laboratory. The ongoing challenge of elastic fiber production is defined.