Trafermin

To review the various basic research and treatments available to regenerate the vocal folds and to discuss the direction for future treatments.

A comprehensive review was performed in PubMed database and Google Scholar utilizing search terms including combinations and variations of the following concepts: vocal fold anatomy, vocal fold disorders, and regenerative therapies. No particular inclusion or exclusion criteria were set due to the nature of this narrative review article.

The regenerative treatments available for each vocal fold layer are the following: 1) epidermal growth factor and transforming growth factor-β1 for the epithelial layer, 2) autologous fibroblasts, autologous bone-marrow derived mesenchymal stem cells (MSCs), autologous adipose tissue-derived stromal vascular fraction (ADSVF), basic fibroblast growth factor (bFGF), collagen-hyaluronic acid nanofiber, pirfenidone, hepatocyte growth factor (HGF), pulsed dye laser (PDL), diode laser, and platelet-rich plasma (PRP) for the lamina propria, 3) bFGF and controlled-release bFGF with autologous fascia, HGF, c-Met agonistic antibody, and PRP for the muscular layer, 4) and bFGF and PRP-loaded nerve guidance conduit for the nerve. Treatments deemed clinically safe with sustained efficacy assessed up to 6 months are HGF and PDL, while bFGF, autologous fibroblasts, autologous bone marrow-derived MSCs, ADSVF, and PRP have been studied up to 12 months.

An ideal regenerative treatment is one that restores the injured or lost components of the vocal fold. The layered structure of the vocal fold allows for several mechanisms of action for these regenerative therapies. Further experimental and clinical studies are warranted, and these would dictate the impact of vocal fold regenerative therapies. Regenerative medicine may soon be at the forefront for treating vocal fold disorders. Clinicians should be open to advancements in treatment and consider the potential of novel therapies to treat specific pathologies.

Owing to its mitogenic and angiogenic characteristics, the use of basic fibroblast growth factor (bFGF) to promote wound healing has been investigated. However, its clinical efficacy has fallen short of expectations due to its instability. Heparin has been reported to stabilize bFGF. Therefore, we hypothesized that the combination of these agents would more effectively promote wound healing than bFGF alone; a single-center, two-arm parallel, single-blind, and a prospective randomized controlled pilot study was therefore performed involving 12 patients who underwent split-thickness skin graft harvesting. To ensure a feasible clinical treatment model, commercially available agents were used. The patients were randomly assigned to either the control group treated with bFGF (n = 6) or the intervention group treated with bFGF and heparin (n = 6) in a 1:1 ratio. The wound area and the wound area variation was assessed each week postoperatively, as was the number of days required for epithelialization. As a supplementary analysis, the least-squares means were calculated using a linear mixed-effects model. The results of this study indicate that the combination of bFGF and heparin may more effectively promote wound healing than bFGF alone, consistent with our hypothesis. A multicenter trial based on these data is ongoing.