Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor Kaoru Omae a , Shin-ichi Kanemaru a,b,c, *, Eiji Nakatani a , Hideaki Kaneda a , Tsutomu Nishimura a , Risa Tona b,d , Yasushi Naito b,d , Atsuhiko Kawamoto a,e , Masanori Fukushima a a Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan b 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 c Department of Otolaryngology, Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan d Department of Otolaryngology, Head and Neck Surgery, Kobe City Medical Center General Hospital, 2-2-1 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan e 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 Auris Nasus Larynx xxx (2017) xxx–xxx A R T I C L E I N F O Article history: Received 27 July 2016 Accepted 24 December 2016 Available online xxx Keywords: Basic fibroblast growth factor Bone conduction Fibrin glue Gelatin sponge Tissue engineering Tympanic membrane perforation A B S T R A C T 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 Æ 20.3 vs 29.4 Æ 21.0 dB, 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. Abbreviations: AE, adverse event; bFGF, basic fibroblast growth factor; CI, confidence interval; SDV, source data verification; TM, tympanic membrane; TMP, tympanic membrane perforation; TMRP, tympanic membrane regeneration procedure. * Corresponding author at: Department of Otolaryngology—Head and Neck Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan. Fax: +81 6 6312 8867. E-mail addresses: k-omae@tri-kobe.org (K. Omae), kanemaru@ent.kuhp.kyoto-u.ac.jp (S.-i. Kanemaru), e-nakatani@tri-kobe.org (E. Nakatani), hkaneda@tri-kobe.org (H. Kaneda), t-nishimura@tri-kobe.org (T. Nishimura), tona_risa@ent.kuhp.kyoto-u.ac.jp (R. Tona), naito@kcho.jp (Y. Naito), kawamoto@fbri.org (A. Kawamoto), mfukushi@tri-kobe.org (M. Fukushima). G Model ANL-2223; No. of Pages 8 Please cite this article in press as: Omae K, et al. Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor. Auris Nasus Larynx (2017), http://dx.doi.org/10.1016/j.anl.2016.12.005 Contents lists available at ScienceDirect Auris Nasus Larynx jo u rn al h om epag e: ww w.els evier.c o m/lo cat e/anl http://dx.doi.org/10.1016/j.anl.2016.12.005 0385-8146/© 2017 Elsevier B.V. All rights reserved.