Novel Biomolecule-Infused Gelatin Injectable for Treatment of Recurrent Laryngeal Nerve Injury.

Abstract

Unilateral vocal fold paralysis (UVFP) due to recurrent laryngeal nerve injury (RLN) is a major cause of voice disorders. We have recently identified three biomolecules (agrin, acetylcholine, and neuregulin) with the potential to promote reinnervation after RLN injury. This study aimed to determine if a gelatin injectable with the reinnervating biomolecules will induce site-specific amplification of neurotrophic factor release and reinnervation after RLN injury in unilateral vocal fold paralysis. C57BL/6 mice underwent RLN transection with the following treatment allocations: saline control (N = 16), biomolecule cocktail only (N = 16), and biomolecule-infused gelatin (N = 16). All injectables were delivered into the denervated thyroarytenoid muscle. Assessment of glottic function was determined via laryngeal electromyography (L-EMG) and stimulated video laryngoscopy post-RLN transection on days 7 and 28. Histopathology analysis via immunohistochemistry (IHC) and genetic analysis via quantitative polymerase chain reaction (qPCR) were utilized to characterize reinnervation and gene expression changes within the harvested larynges. Both biomolecule treatment groups had enhanced reinnervation of the adductor complex, as indicated by higher stimulated L-EMG area under the curve (p < 0.001), adduction during stimulation (p < 0.002), midline resting position (p < 0.002), and the presence of innervated neuromuscular junctions on IHC. qPCR results suggest both biomolecule treatments resulted in elevated neurotrophic and angiogenic factor expression from the injected muscle. Injectable biomolecule-infused gelatin may serve as a novel long-term therapeutic for glottic functional restoration by redirecting existing mechanisms of synkinesis via site-specific neurotrophic factor release. N/A.