Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor

Kaoru Omae; Shin-Ichi Kanemaru; Eiji Nakatani; Hideaki Kaneda; Tsutomu Nishimura; Risa Tona; Yasushi Naito; Atsuhiko Kawamoto; Masanori Fukushima

doi:10.1016/j.anl.2016.12.005

Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor

Auris Nasus Larynx. 2017 Dec;44(6):664-671. doi: 10.1016/j.anl.2016.12.005. Epub 2017 Jan 22.

Authors

Kaoru Omae¹, Shin-Ichi Kanemaru², Eiji Nakatani³, Hideaki Kaneda⁴, Tsutomu Nishimura⁵, Risa Tona⁶, Yasushi Naito⁷, Atsuhiko Kawamoto⁸, Masanori Fukushima⁹

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.

PMID: 28119094
DOI: 10.1016/j.anl.2016.12.005

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.

Conclusion: 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).

Keywords: Basic fibroblast growth factor; Bone conduction; Fibrin glue; Gelatin sponge; Tissue engineering; Tympanic membrane perforation.

Publication types

Clinical Trial
Multicenter Study

MeSH terms

Adult
Aged
Female
Fibrin Tissue Adhesive / therapeutic use
Fibroblast Growth Factor 2 / therapeutic use*
Gelatin Sponge, Absorbable / therapeutic use*
Humans
Male
Middle Aged
Regeneration*
Tissue Adhesives / therapeutic use
Treatment Outcome
Tympanic Membrane / surgery*
Tympanic Membrane Perforation / therapy*
Young Adult

Substances

Fibrin Tissue Adhesive
Tissue Adhesives
Fibroblast Growth Factor 2