Engineering functional vocal cord tissue

Voice impairments are often the result of damage to the vocal folds in the larynx, which is pictured here in orange.Eraxion/iStock/Thinkstock

Your voice is as unique as your fingerprint. It helps define your personality, mood, and health. Your ability to talk—as well as to laugh, sing, and cry—results from airflow from your lungs pushing past your vocal cords (folds) with enough pressure to cause them to vibrate. The vocal folds are a pair of rubber band-like tissues located in your larynx (voice box) directly above the windpipe (trachea). They’re made of up several layers of cells, including muscle and an elastic layer, known as the mucosa.

About 20 million Americans suffer from voice impairments, often as a result of damage to the vocal folds. Treatment options are currently limited. A team led by Dr. Nathan Welham at the University of Wisconsin-Madison set out to engineer tissue that could mimic the functions of vocal folds. Their work was funded in part by NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Allergy and Infectious Diseases (NIAID), and other NIH components. The study appeared on November 18, 2015, in Science Translational Medicine.

The researchers obtained vocal cord cells (fibroblasts and epithelial cells) from human donors. They reasoned that tissue already exposed to the mechanical forces associated with making sound would be more likely to develop functional characteristics when grown in culture.

They purified the cells and grew them on 3D scaffolds. The cells gradually developed features similar to human vocal fold mucosa, including forming layers with differing characteristics. Protein composition analysis revealed that the engineered mucosa contained many of the same proteins found in normal vocal cords.

To determine whether the engineered tissue could transmit sound, the researchers grew human-sized vocal fold mucosa. They grafted these onto 1 side of voice boxes removed from donor dogs, were the opposite side had a normal healthy vocal fold. When warm, humidified air was blown through an attached artificial windpipe, the engineered tissue produced sounds. High-speed digital imaging showed that the engineered tissue vibrated in a pattern similar to regular tissue. The scientists also grafted the engineered tissue into mice that had human immune systems. The tissue was well tolerated, suggesting it may have transplant potential.

“Voice is a pretty amazing thing, yet we don’t give it much thought until something goes wrong,” Welham says. “Our vocal cords are made up of special tissue that has to be flexible enough to vibrate, yet strong enough to bang together hundreds of times per second. It’s an exquisite system and a hard thing to replicate.”

The safety and long-term function of the engineered tissue will continue to be evaluated. Due to the scarcity of vocal fold human cells, other cell types, such as stem cells, are also being explored as a source for vocal fold development.