Dysphonia, or voice problems, is a disorder that gets little attention in the public imagination. Loss of speech is not life-threatening. And because it is often a consequence of other health issues such as cancer that are life-threatening, those other issues are what get the attention.

But it affects a surprising number of Americans – roughly 20 million. And though many of those cases are transient, chronic dysphonia "can have a devastating impact on the effectiveness and ease of communication with loved ones, in social situations, in the workplace, and in the marketplace," corresponding author Nathan Welham told reporters.

Voice conveys both factual information and emotion. And it is "something we often give little thought to unless we're having trouble with its production," he said.

Welham, who is a speech-language pathologist at the University of Wisconsin at Madison, was speaking at a press conference where he and his colleagues presented bioengineered vocal fold tissues that could offer a solution to those communications problems.

Ironically, developing such tissue for transplantation was not the team's original goal. "At the outset, we never imagined that we would see the impressive level of function that we did and that this engineered tissue created with actual human vocal fold cells would have such strong potential as a therapy in its own right," Welham said.

Instead, what they were trying to develop was a control tissue for other engineering approaches to develop artificial vocal chords.

They published their work in the Nov. 18, 2015, issue of Science Translational Medicine.

Voice, Welham said, is "generated by a complex and beautiful system."

That system has some stringent biomechanical requirements. Vocal folds, which are often called vocal chords have to be both strong enough to form an airtight barrier and flexible enough to vibrate hundreds to thousands of times per second.

In their work, Welham and his colleagues generated the vocal folds by co-culturing two cell types, human vocal fold fibroblasts and epithelial cells.

The approach is one of a number of attempts in recent years to bioengineer organs to address the constant shortage of donor organs for transplantation.

It bears some similarities both to British company Videregen Ltd. and to tissue engineering techniques being developed in academic labs. (See BioWorld Today, Nov. 5, 2015, Sept. 30, 2015, and April 25, 2013.)

They analyzed the resulting tissues both from a proteomics as well as a functional standpoint.

Proteomics analysis showed that most of the proteins produced in patient-derived vocal fold tissue were present in the engineered tissue. The team also saw "proteins that were not present when either type of cell was cultured alone in the scaffold," co-author Brian Frey told reporters.

Those proteins were an indication that fibroblasts and epithelial cells were "thriving" in the culture conditions, he said. "They're effectively talking to each other and producing the structural proteins that make this special tissue capable of vibration."

He concluded that the engineered vocal chords are an example of "tissue engineering where biology does most of the work."

Ex vivo experiments showed that the tissue could vibrate and withstand the sorts of mechanical forces that would be necessary for sound production, and indeed, that they could produce sound when air was blown over them.

The team also transplanted the tissues into mice with a humanized immune system, since "even a functionally perfect tissue can be rejected in a matter of minutes to hours by a vigorous immune response," co-author Matthew Brown, a graduate student at the University of Wisconsin at Madison, told reporters.

The vocal fold tissue, however, was less immunogenic than the authors expected. At least in short-term experiments, "to our surprise, not only did the engineered vocal fold tissue appear to be tolerated by the patient's own immune cells, but also vocal fold tissue derived from a third party unrelated individual was not rejected by the patient's immune cells," Brown said. The team is currently testing the longer-term immunogenicity of the tissue.