Research ArticleTissue Engineering

Bioengineered vocal fold mucosa for voice restoration

Science Translational Medicine  18 Nov 2015:
Vol. 7, Issue 314, pp. 314ra187
DOI: 10.1126/scitranslmed.aab4014

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Getting vocal about tissue engineering

The power of the voice cannot be disputed. For instance, Adele’s lyrics would not elicit chills (or tears) without strategic pitch and harmonizing known as appoggiatura; the chant “Yes we can” garnered more than 69 million popular votes to win Obama the 2008 presidential election; and, more simply, voice is the primary means we all use to communicate with co-workers, loved ones, and the rest of society. Dysphonia—or difficulty speaking from vocal fold tissue damage or loss—can impair one’s ability to be an effective communicator. To provide a new option for those with dysphonia, Ling et al. used two different types of human vocal fold cells to create a functional mucosa. When grafted into the dog larynx ex vivo, the engineered vocal fold reproduced natural physiology, including the vibrations necessary to transmit sound. In vivo, in humanized mice, the engineered mucosa was tolerated by functional human immune cells. These data suggest feasibility for transplant and survival in the larynx as well as for function, ultimately giving patients back their voices.

Abstract

Patients with voice impairment caused by advanced vocal fold (VF) fibrosis or tissue loss have few treatment options. A transplantable, bioengineered VF mucosa would address the individual and societal costs of voice-related communication loss. Such a tissue must be biomechanically capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration and physiologically capable of maintaining a barrier against the airway lumen. We isolated primary human VF fibroblasts and epithelial cells and cocultured them under organotypic conditions. The resulting engineered mucosae showed morphologic features of native tissue, proteome-level evidence of mucosal morphogenesis and emerging extracellular matrix complexity, and rudimentary barrier function in vitro. When grafted into canine larynges ex vivo, the mucosae generated vibratory behavior and acoustic output that were indistinguishable from those of native VF tissue. When grafted into humanized mice in vivo, the mucosae survived and were well tolerated by the human adaptive immune system. This tissue engineering approach has the potential to restore voice function in patients with otherwise untreatable VF mucosal disease.

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