Regenerative treatment for tympanic membrane perforation using gelatin sponge with basic fibroblast growth factor.
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).
['Omae|Kaoru|K|', 'Kanemaru|Shin-Ichi|SI|', 'Nakatani|Eiji|E|', 'Kaneda|Hideaki|H|', 'Nishimura|Tsutomu|T|', 'Tona|Risa|R|', 'Naito|Yasushi|Y|', 'Kawamoto|Atsuhiko|A|', 'Fukushima|Masanori|M|']
D000328:Adult D000368:Aged D005260:Female D015718:Fibrin Tissue Adhesive D016222:Fibroblast Growth Factor 2 D005781:Gelatin Sponge, Absorbable D006801:Humans D008297:Male D008875:Middle Aged D012038:Regeneration D014014:Tissue Adhesives D016896:Treatment Outcome D014432:Tympanic Membrane D018058:Tympanic Membrane Perforation D055815:Young Adult
Tympanic membrane perforation Gelatin sponge Basic fibroblast growth factor Fibrin glue Bone conduction Tissue engineering