Vocal Fold Injection of Absorbable Materials: A Histologic Analysis With Clinical Ramifications

Abstract

Gels composed of carboxymethylcellulose (CMC) and cross-linked hyaluronic acid are commonly used as temporary or resorbable injectable materials for vocal fold medialization. However, there is limited information about tissue injection patterns, soft tissue reaction, degradation, and residence time, particularly for the newer CMC gels. Prospective, laboratory. Ten canines underwent paraglottic (deep to the vocal ligament) microlaryngoscopic injection with about 100 µL (0.1 mL) of cross-linked hyaluronic acid (Restylane) in the right vocal fold and about 100 µl (0.1 mL) of CMC gel in the left vocal fold. Two commercial CMC gels of similar formulation (Prolaryn Gel and Renú Gel) were used in 5 animals each. Two subjects were sacrificed for histologic analysis at 3, 13, 29, 42, and 55 days. Histology showed that injected Restylane formed cohesive ovoid-shaped aggregated implants with minimal dispersion, inflammation, or cellular invasion in all subjects. Approximately 86% of Restylane injected remained at 8 weeks, as estimated from postmortem, high-resolution magnetic resonance imaging scans. In contrast, histology showed that both CMC gels dispersed widely through fascial planes during and after injection within and outside the thyroarytenoid muscle fascicles. There was a robust macrophage and histiocyte phagocytic response, with moderate to severe inflammation noted around residual CMC gel at early time points, and at 6 to 8 weeks, very little free gel was observed. None of the studied materials induced a clinical inflammatory reaction on laryngoscopy such that they would be considered problematic or dangerous. Restylane demonstrated superior injection localization, tissue compatibility, and residence time. Both CMC gels did not localize well in the paraglottic region, and there was a robust inflammatory response, with clearance by macrophages and short residence time. These results suggest that CMC gels may have a more limited application than previously thought for vocal fold medialization in patients in whom the injection is being used to achieve voice enhancement while awaiting reinnervation. Level of Evidence: NA.