Silk Protein Microparticle-based Filler for Injection Augmentation

Vocal fold paralysis is a clinical condition that arises commonly as a complication of
surgery, endotracheal intubation, malignancy, or idiopathic etiologies. It often results in
glottal insufficiency, which is the inability of the true vocal folds to meet and achieve
complete closure during normal physiologic functions such as speech, swallowing, and
coughing. The presence of vocal fold paralysis with glottal insufficiency can lead to
decreased quality-of-life, as well as increase risks of complications such as aspiration
pneumonia.

Current treatments for vocal fold paralysis are based around techniques to medialize the
paralyzed vocal fold. One manner in which this is done is via injection of a filler or
bulking agent into the vocal fold in order to augment it. Injection augmentation has many
advantages including its minimally invasive nature, overall safety and low risk/complication
rate, immediate clinical effect, and ability to perform it at the bedside or in-office.
Various materials are used for injection augmentation including autologous fat, hyaluronic
acid, collagen, carboxymethylcellulose, and calcium hydroxyapatite. However, all of the
current injection choices have individual limitations such as temporary effect,
unpredictability due to variable resorption by the body, unfavorable mechanical properties,
and challenging handling attributes.

Silk is derived from the Bombyx mori silk worm and has a long history as a surgical
biomaterial. Surgical scaffolds derived from silk have been used for reconstructive surgery,
due to its ability to allow cellular infiltration and encourage tissue
regeneration/remodeling. Given the potential advantages of such a material, Brown et al
engineered and studied a novel silk protein microparticle-based filler material suitable for
injection augmentation.

Patients with unilateral vocal fold paralysis identified at the study sites will be offered
participation in this study to receive injection augmentation of the paralyzed vocal fold
with the filler material under investigation. Outcome measures evaluated pre- and
post-injection and over follow-up visits will include various patient reported quality of
life indices, objective clinical assessments of voice, laryngeal videostroboscopy
examinations, and acoustic/aerodynamic testing. The investigators hypothesize that the novel
silk protein microparticle-based filler will have a favorable safety profile for use as an
injectable material in the human larynx and it will produce durable clinical benefit lasting
up to 12 months.

Inclusion Criteria:

- Unilateral vocal fold immobility with glottal insufficiency present for at least 2
weeks from onset

- Willingness to partake in study and follow-up as documented by signed informed consent

Exclusion Criteria:

- History of allergy/hypersensitivity to silk or silk containing products

- History of allergy/hypersensitivity to hyaluronic acid (HA) or HA containing products

- History of allergy/hypersensitivity to lidocaine or amide-based anesthetics

- History of an autoimmune condition

- Significant immunocompromised state (i.e. immunosuppression s/p transplantation)

- Pregnancy

- Active infection or inflammation in the larynx

- Comorbid known laryngeal conditions including but not limited to vocal fold scar,
vocal tremor, laryngeal dystonia, etc. that would warrant other interventions for
optimal treatment

- History of laryngeal surgery

- History of previous vocal fold injection augmentation

- Life expectancy of less than 6 months