Researchers have engineered a new hydrogel that shows early promise as a treatment for patients with vocal fold disorders.

The hydrogel lasts longer than currently available treatments, which could reduce the need for repeated administration. It is intended to promote vocal fold mucosal regeneration in patients with scarring and atrophy. 

When injected subcutaneously into rats, the gel demonstrated a strong initial immune response, followed by integration with the surrounding tissue by day 21. It also showed improved stability over previous hydrogels, according to the authors.

The research was published in Biomaterials.

Long-Lasting Gel

As many as 1 in 13 adults in the US experience vocal fold disorders, but only 10% seek treatment. Severe vocal fold disorders such as paralysis, atrophy, and scarring can result from aging, heavy voice use, or surgical resection and lead to disability in speaking, swallowing, or breathing, the authors noted.

“Common injectables for vocal cords are short-lived in the tissue due to resorption or may cause tissue stiffening after injection,” co-author Nicole Li-Jessen, PhD, associate professor of communication sciences and disorders at McGill University in Montreal, told Medscape Medical News.

“For severe vocal cord injuries, like sulcus vocalis or atrophy, the gel needs to stay long enough to give cells time to restore, repair, and regenerate. Vocal cords are very soft tissue and vibrate over hundreds of times per second when we speak, and so there remains a tissue engineering challenge in how to create a bioactive material that possesses regenerative capacity, is durable, and does not significantly alter the local tissue’s mechanical function after injection,” Li-Jessen said.

“Usually, people who need these injections have vocal field scarring or atrophy. Atrophy is common in the elderly, with around 7% having some atrophy after age 65 years,” she said.

The gel is made of decellularized extracellular matrix (dECM), a natural biomaterial derived from human or animal tissue by removing the cells and acellular antigens, Li-Jessen explained.

“One great advantage of dECM is that it provides a natural environment that cells are already familiar with and can function effectively in. The dECM materials have shown excellent regenerative potential by minimizing the foreign body response, stimulating vascularization, and promoting extracellular matrix remodeling,” she said.

To make the dECM materials into a gel that could be injected, the researchers used a technique called click chemistry to link the polymer chains into a network to form a stable gel at physiologic conditions, co-author Maryam Tabrizian, PhD, professor of biomedical engineering at McGill University, told Medscape Medical News.

“This technique allows us to have spatial and temporal control over gelatin. Thanks to the click chemistry, our gel was found to have slower degradation than those with no click crosslinking. When we injected the gel under the skin of rats, it showed a good integration with surrounding tissue for up to 21 days,” Tabrizian said.

“We hope this new biomaterial can support more permanent tissue restoration that would reduce the need for repeated injections,” added Li-Jessen. “Of course, further material evaluations are needed. So far, the effectiveness of our click dECM-alginate gel has only been tested in vitro and in an animal model.”

Human Trials Next

The FDA has increasingly emphasized nonanimal testing methods to evaluate medical devices. “To move forward, we will further test the new hydrogel in our in-house computational models of vocal fold injuries to fine-tune the design of the gel,” said Li-Jessen.

The next step will be to test the gel in human trials. 

“If successful, our work could pave the way for a minimally invasive, longer-lasting treatment for voice loss,” Li-Jessen said.

“Vocal cord injuries are especially common among older adults who have acid reflux or who smoke and people who use their voices professionally, such as teachers, singers, and radio hosts.”

Li-Jessen, who in addition to being a clinician and scientist, is a pianist who works with singers, says she has seen how devastating voice loss can be for performers.

“People take their voices for granted, but losing your voice can deeply affect mental health and quality of life, especially for those whose livelihoods depend on it,” she said.

A ‘Fantastic’ Idea

Commenting on the study for Medscape Medical News, Joshua Silverman, MD, PhD, chief of laryngology for Northwell Health in New Hyde Park, New York, said, “This is still experimental work; the gel has not been tested in humans, but I think the idea behind it is fantastic.” Silverman did not participate in the research.

“I do a lot of vocal fold injections for voice and vocal cord paralysis issues, and so I use these fillers on a weekly basis. If we can figure out a way to have them last longer, that’s fantastic, but we’re not there yet,” Silverman said.

Injections usually last between 6 and 12 months, he said. 

“There are a few different types of material, and depending on the voice requirements and the reason for doing the injection, we can use either the shorter-acting or the longer-acting injection material. The longest-lasting gels usually last about a year, but I have some patients I injected 7 years ago, and the gel is still working. So, it’s not a guarantee that an injection loses its effectiveness,” Silverman said. But for the treatment of vocal fold scarring and atrophy, which is the application for which the present gel was developed, such longevity would be counterproductive. 

“It’s promising in an animal model, but it’s nowhere near prime time yet. And we do have materials that last,” he added.

The study was supported by the National Sciences and Engineering Research Council of Canada, Canada Research Chair research stipends, and the National Institutes of Health. Li-Jessen, Tabrizian, and Silverman reported having no relevant financial relationships.