Abstract
Patients with laryngeal disorders may have severe morbidity relating to swallowing, vocalization, and respiratory function, for which conventional therapies are suboptimal. A tissue‐engineered approach would aim to restore the vocal folds and maintain respiratory function while limiting the extent of scarring in the regenerated tissue. Under Good Laboratory Practice conditions, we decellularized porcine larynges, using detergents and enzymes under negative pressure to produce an acellular scaffold comprising cartilage, muscle, and mucosa. To assess safety and functionality before clinical trials, a decellularized hemilarynx seeded with human bone marrow‐derived mesenchymal stem cells and a tissue‐engineered oral mucosal sheet was implanted orthotopically into six pigs. The seeded grafts were left in situ for 6 months and assessed using computed tomography imaging, bronchoscopy, and mucosal brushings, together with vocal recording and histological analysis on explantation. The graft caused no adverse respiratory function, nor did it impact swallowing or vocalization. Rudimentary vocal folds covered by contiguous epithelium were easily identifiable. In conclusion, the proposed tissue‐engineered approach represents a viable alternative treatment for laryngeal defects. Stem Cells Translational Medicine 2017;6:677–687
Highlights
There are no satisfactory conventional solutions for patients with end-stage laryngeal structural disorders, which can result from trauma or cancer resection
The clinical need does not necessarily demand this, because we did not replace the whole larynx. We proposed that this technology would provide functional replacement in terms of airway, voice, and swallowing in a manner superior to that provided by present techniques
The use of negative pressure combined with hyper- and hypotonic solutions followed by enzymatic/detergents has not, to our knowledge, been previously reported
Summary
There are no satisfactory conventional solutions for patients with end-stage laryngeal structural disorders, which can result from trauma or cancer resection. This has profound impact on quality of life, especially with respect to swallowing, breathing, and speech. Of the 2,000 individuals diagnosed annually with laryngeal cancer in the U.K., 800 undergo local resection that leaves permanent defects in the vocal cords and hoarseness; the 500 most advanced cases have their larynx removed completely; the remainder undergo chemoradiotherapy, which achieves good cure rates but has high morbidity, 5% mortality, and can leave a functionless larynx [1]. Evidence has shown that most of the larynx can be removed with preservation of vocal and sphincter functions, provided one side retains movement (i.e., the “cricoarytenoid-nerve-muscle” unit) [2, 3]
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