The Efficacy of Fibroblast Growth Factor for the Treatment of Chronic Vocal Fold Scarring: From Animal Model to Clinical Application

Abstract

ObjectivesThis study assessed the regenerative efficacy of basic fibroblast growth factor (FGF) in a rabbit model of chronic vocal fold scarring and then confirmed its utility and safety in a prospective trial of patients with this condition.MethodsFGF was injected three times, at 1-week intervals, into a chronic vocal fold scar created in a rabbit model. After 1 month, mRNA level of procollagen I, hyaluronic acid synthetase 2 (HAS 2), and matrix metalloproteinase 2 (MMP 2) were analyzed by real-time polymerase chain reaction. The relative densities of hyaluronic acid (HA) and collagen were examined 3 months post-injection. From April 2012 to September 2014, a prospective clinical trial was conducted at a tertiary hospital in Korea. FGF was injected into the mild vocal fold scar of 17 consecutive patients with a small glottic gap. The patients underwent perceptual, stroboscopic, acoustic aerodynamic test, and Voice Handicap Index (VHI) survey prior to and 3, 6, and 12 months after FGF injection.ResultsFGF injection of the vocal fold scar decreased the density of collagen and increased mRNA level of HAS 2 and MMP 2 expression significantly compared to the control group injected with phosphate buffered solution in a rabbit model (P<0.05). In the clinical trial, significant improvements in the majority of the subjective and objective voice parameters were registered 3 months after FGF injection and were maintained at 12 months. Complications associated with the FGF injections, such as granuloma, were not observed during the follow-up period.ConclusionBased on the animal model and the prospective clinical trial, vocal fold injections of FGF in patients with mild chronic vocal fold scarring can significantly improve voice quality for as long as 1 year and without side effects. Our results recommend the use of FGF vocal fold injection as an alternative treatment modality for mild chronic vocal fold scarring.

The effects of cryotherapy on vocal fold healing in a rabbit model

“…Second, the rabbit animal model is chosen to investigate vocal fold wound healing because it possesses a histology of the LP similar to that of humans. Three months in the life of a rabbit is similar to several years in humans; therefore, our animal study based on 3 months was able to demonstrate the long‐term effect of cryotherapy on the mature wound‐healing phase. However, the translation of findings from the rabbit model to human vocal fold is tenuous.…”

In vitro evaluation of anti‐fibrotic effects of select cytokines for vocal fold scar treatment

“…Prolonged retention may circumvent problems associated with multiple dosing (i.e. cost and secondary injuries). Since no cytokine in our study (HGF, IL‐10, and IL‐6) requires internalization to change cell behaviors, covalently tethering of these molecules is believed to prolong their effective dosage.…”

“…Both cytokines have demonstrated the capacity to improve LP biomechanical properties in vivo , reverse undesirable ECM production such as collagen and α‐SMA, and promote hyaluronic acid expression both in vitro and in vivo . While simple and partially effective, cytokine injections are limited by rapid in vivo absorption and potential need for multiple dosing, potentially causing secondary injuries and further exacerbating scar formation . To prolong cytokine retention, different biomaterial‐based loading systems have been developed, successfully extending release up to 1 month in vivo .…”

Efficacy of fibre‐optic laryngeal potassium titanyl phosphate laser surgery under local anaesthesia for the treatment of vocal polyps: A prospective study of 65 patients

“…Endoscopic and videostroboscopic results were obtained via a stroboscope (Model 9100; Kay Pentax). Glottal closure and the mucosal wave were evaluated using a previously reported …”