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Transforming growth factor β3 for the prevention of vocal fold scarring


  • This study was supported by MEXT KAKENHI (21592192, 23592480, 22591907, 22791596), Mitsui Sumitomo Insurance Welfare Foundation, and the National Institute of Biomedical Innovation. The authors have no other funding, financial relationships, or conflicts of interest to disclose.



Vocal fold scarring poses a therapeutic challenge. It causes hoarseness and decreases the quality of life. Transforming growth factor β3 (TGFβ3) is highly expressed in fetal wounds that heal without scarring, and administration of TGFβ3 has been reported to prevent scarring of the skin and the buccal mucosa. Thus TGFβ3 is considered to be a key molecule in scar-free healing. This study aimed to examine the ability of TGFβ3 to prevent vocal fold scarring, with particular attention paid to the distribution of extracellular matrices and functional outcomes.

Study Design:

Prospective study using an animal model.


Ten beagles were used in this study; 500 μL of TGFβ3 (0.5 μg/mL: 5 beagles) or saline (5 beagles) was injected into the vocal fold lamina propria. Fifteen minutes after injection, vocal folds were injured by stripping off the entire layer of the lamina propria. Six months after surgery, animals were euthanized and the larynges were harvested. Vibratory and histologic examinations were performed.


The administration of TGFβ3 suppressed granulation-tissue formation and scarring. TGFβ3-treated vocal folds showed significantly better vibratory properties, resembling normal vocal folds. Histologic analysis revealed favorable restoration of elastin and hyaluronic acid in the lamina propria. The distribution of collagen was well organized, and collagen deposition was less dense in TGFβ3-treated vocal folds compared to sham-treated vocal folds.


Administration of TGFβ3 before injury significantly suppressed scar formation and induced favorable restoration of extracellular matrices in the vocal fold lamina propria, resulting in much improved phonatory function.