title: Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor.
abstract: OBJECTIVE
  The objective of this study was to evaluate safety and efficacy of regenerative treatment using gelatin sponge with basic fibroblast growth factor (bFGF) in patients with tympanic membrane perforation (TMP).
  
  
  METHODS
  The current study was a prospective, multicenter, open-label, single-arm, and exploratory clinical trial to evaluate the safety and efficacy of the TM regeneration procedure (TMRP). Myringotomy was used to mechanically disrupt the edge of the TMP, and a gelatin sponge immersed in bFGF was then placed over the perforation. Fibrin glue was dripped over the sponge as a sealant. TMP closure was examined 4 weeks later and, if insufficient, TMRP was repeated a maximum of three more times. TMP closure and hearing improvement 12 weeks after the final TMRP as well as safety were evaluated.
  
  
  RESULTS
  Of the 11 patients with TMP who participated in this study, one who fulfilled the exclusion criteria and did not undergo TMRP and one with cholesteatoma were excluded from the efficacy analysis. TMP closure and hearing improvement 12 weeks after the final TMRP were achieved in eight out of nine patients (88.9%). Mean bone conduction threshold significantly improved 12 weeks after the TMRP compared with baseline (35.7±20.3 vs 29.4±21.0dB, P=0.015). Six out of ten patients receiving TMRP experienced temporary adverse events: appendicitis (serious, severe), otorrhea (mild), otitis media (mild), and sudden hearing loss (mild). However, none were related to the protocol treatment.
  
  
  CONCLUSIONS
  TMP closure and hearing improvement were frequently confirmed following the TMRPs which were safely performed. These favorable outcomes were accompanied with significant improvement of the bone conduction threshold. These promising outcomes would encourage a large-scaled, randomized and pivotal clinical trial in the future. This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000006585).
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: k-omae@tri-kobe.org.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Omae
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Electronic address: kanemaru@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Kanemaru
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: e-nakatani@tri-kobe.org.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakatani
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: hkaneda@tri-kobe.org.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: t-nishimura@tri-kobe.org.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-2-1 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: tona_risa@ent.kuhp.kyoto-u.ac.jp.
authors.forename: Risa
authors.initials: R
authors.lastname: Tona
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-2-1 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: naito@kcho.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan; Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: kawamoto@fbri.org.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
authors.affiliation: Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: mfukushi@tri-kobe.org.
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000627:therapeutic use; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D005781:Gelatin Sponge, Absorbable / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012038:Regeneration; D014014:Tissue Adhesives / Q000627:therapeutic use; D016896:Treatment Outcome; D014432:Tympanic Membrane / Q000601:surgery*; D018058:Tympanic Membrane Perforation / Q000628:therapy*; D055815:Young Adult
chemical_list: D015718:Fibrin Tissue Adhesive; D014014:Tissue Adhesives; D016222:Fibroblast Growth Factor 2
keywords: Basic fibroblast growth factor; Bone conduction; Fibrin glue; Gelatin sponge; Tissue engineering; Tympanic membrane perforation