A tissue-engineered implant for reconstructing part of the larynx has produced good results in vitro and in a canine, according to findings presented at the 2022 Triological Society Combined Sections Meeting in January 2022.
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March 2022The implant—the result of 10 years of work, according to the researchers—dangles the prospect of a new reconstruction option for laryngeal cancer. Total laryngectomies are frequently performed not because the cancer involves the entire larynx, said David Lott, MD, chair of the division of laryngology and professor of otolaryngology at the Mayo Clinic in Arizona, but because the defect that results after cancer removal is not able to be reconstructed in a way that provides normal laryngeal function. This implant allows for patient-specific reconstruction of hemilaryngeal or partial laryngeal defects to improve functional results, hopefully resulting in the need for fewer total laryngectomies. The effort earned the society’s Honorable Mention for Basic Science Award.
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“Total laryngectomy has many qualityof- life issues associated with it,” said Dr. Lott. “Hemilaryngectomy is oncologically sound and can circumvent many of the quality-of-life issues seen with total laryngectomy. The problem is, hemilaryngectomy has fallen out of favor to some degree with many surgeons due to the difficulty of achieving good laryngeal function after surgery.”
Part of the reason for this, he said, is that it’s difficult to recreate the patient-specific anatomy of the larynx, that multiple revisions might be needed for proper function, and that even then “sometimes we’re never really able to restore proper laryngeal function for these patients.”
Tissue-Engineered Larynx Replacement
Dr. Lott’s lab is setting out to develop a tissue-engineered larynx replacement that’s specific to the patient, is permanent, and is completely integrated biologically, while also restoring much of the original function. The replacement is able to be implanted in about three weeks.
“We developed a 3D-printed polyethylene scaffold that is somewhat modifiable,” Dr. Lott said. “If you wanted to medialize that vocal fold structure, you can make those modifications in the software.” Polyethylene was used for the scaffold material, he said, because it has a history of use in the head and neck area, is a permanent structure, holds its shape, and can be biointegrated with the patient’s anatomy.
With their first implant, researchers rearranged tissue, using flaps and other methods, to cover the implant. That patient is now four years past implantation and has done well. Photos displayed during the presentation showed nearly symmetrical halves of the larynx, one native and the other reconstructed, with only a small gap posteriorly on the reconstructed side.
“Aside from the gap posterially, you really can’t tell the difference between the two sides,” Dr. Lott said. On a video, the woman can be heard reading, with good voice quality.
“We know that that proof of concept is there—that we can use that three-dimensional shape, we can get function, and we didn’t need to do a laryngectomy for her,” he said. That procedure has now been performed in a total of six patients, he added.
Then, Dr. Lott’s group moved on to a tissue-engineered implant so that tissue would grow over the scaffolding “to decrease the morbidity, decrease intraoperative time, and decrease the variability involved with flaps and tissue rearrangement.”
They turned to a canine model, using adipose-derived stem cells that were removed from the canine. They then cellularized the scaffold with a concentration of about 3 million cells. The cells were in a fibrin gel that would help move them into the porous material of the implant and then grow across its surface. Researchers then put the cellularized scaffold into the canine model and assessed the progress (Lott DG, et al. A tissue engineered construct for laryngeal regeneration: a proof-ofconcept device design study. Laryngoscope. Jan 27, 2022. Published online ahead of print).
“We’ve shown we can 3D print and mold these structures,” Dr. Lott said. “We decided to go with a molded structure because it’s easier to show the ability for it to maintain its parameters for the FDA.”
Hemilaryngectomy is oncologically sound and can circumvent many of the quality-oflife issues seen with total laryngectomy. The problem is, hemilaryngectomy has fallen out of favor to some degree with many surgeons due to the difficulty of achieving good laryngeal function after surgery. —David Lott, MD
Dr. Lott displayed pictures of the progression during his Triological meeting presentation that showed that by 12 months, the implant was completely covered with epithelium except for the medial portion of the vocal fold—a 3-mm area that had not epithelialized.
Nonetheless, the procedure was considered successful. The airflow and subglottal pressure were within normal limits, and acoustic signaling showed that there was strong harmonic content to the dog’s bark. On a sound clip, the dog’s bark sounds like a typical bark. There were also no swallowing or breathing problems. There was never any infection, and the canine thrived throughout the study, he said.
“I think part of the reason why it didn’t completely epithelialize is that the dog’s barking and coughing caused both strong tangential airflow across the surface and direct trauma to the surface from the normal vocal fold,” Dr. Lott explained. When they removed the implant, the muscle had pulled away from the concave component of it so that there wasn’t good vascularization, he said.
Dr. Lott’s Head and Neck Regenerative Medicine Laboratory was recently awarded an NIH R01 grant to continue the effort. The lab is a translational lab specifically designed for bench work innovation that can be directly applied to clinical medicine. Implants will be placed in 10 canines as a part of that study, Dr. Lott said.
“We thought that this was a success—mostly,” he said. “We really wish that the medial part of the vocal fold would have completely epithelialized. But we had excellent functional results.” He said his team is confident that the lessons learned from this study will help to ensure complete epithelialization and even better functional results in the larger preclinical study. Success with this ongoing study, he said, will enable a human clinical trial.
Thomas R. Collins is a freelance medical writer based in Florida.