title: Drug delivery system of basic fibroblast growth factor using gelatin hydrogel for restoration of acute vocal fold scar.
abstract: OBJECTIVE
  There continue to be therapeutic challenges in the management of vocal fold scarring. We previously showed that basic fibroblast growth factor (bFGF) injection has therapeutic potential for vocal fold scarring. However, the working time of bFGF is relatively short, and multiple injections were required in many cases to obtain the regenerative effect. An efficacious delivery system for bFGF has yet to be established. We designed a method of sustained drug delivery system (DDS) of bFGF by using a gelatin hydrogel. Hydrogel has been developed for targeted delivery and controlled release of bFGF. Hydrogel of the particle type is also injectable and commercially available. The current study aims to investigate the effects of a single injection of bFGF-DDS on acute vocal fold scarring using a canine model.
  
  
  METHODS
  Vocal folds from eight beagles were unilaterally scarred by stripping the lamina propria. One month later, hydrogels (0.5ml) containing 10μg of bFGF were injected into the scarred vocal folds of four beagles (FGF-hydrogel group). Saline (0.5ml) was injected into the other four beagles (sham group). Vibratory and histological examination of excised larynges was performed 5 months after treatment. Comparative analysis between the current data and our previous data with repeated injection of bFGF solution was also completed.
  
  
  RESULTS
  Vibratory examination demonstrated significantly improved vibration in the bFGF hydrogel-treated group. Histological examination of the bFGF hydrogel group showed restoration of hyaluronic acid in the lamina propria as compared to sham. Comparison between the DDS system and our previous bFGF solution injection indicated better effects of the DDS system on vibratory amplitude.
  
  
  CONCLUSIONS
  A single injection of bFGF hydrogel has regenerative effects on acute vocal fold scarring, which is at least similar to repeated injection of bFGF solution.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Otorhinolaryngology, The Jikei University, School of Medicine Tokyo, Japan. Electronic address: toshiki-koba@jikei.ac.jp.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: m_mizuta@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Mizuta
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: n_hiwatashi@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Nao
authors.initials: N
authors.lastname: Hiwatashi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: y_kishimoto@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Yo
authors.initials: Y
authors.lastname: Kishimoto
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. Electronic address: nakamura@frontier.kyoto-u.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, Osaka, Japan. Electronic address: kanemaru@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Kanemaru
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: hirano@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hirano
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000188:drug therapy*; D004285:Dogs; D016503:Drug Delivery Systems; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D005780:Gelatin; D006820:Hyaluronic Acid / Q000378:metabolism; D020100:Hydrogels; D009092:Mucous Membrane / Q000187:drug effects*; D012038:Regeneration / Q000187:drug effects*; D014732:Vibration; D014827:Vocal Cords / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D020100:Hydrogels; D016222:Fibroblast Growth Factor 2; D005780:Gelatin; D006820:Hyaluronic Acid
keywords: Basic fibroblast growth factor; Drug delivery system; Hydrogel; Vocal fold scar