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Novel Therapy for Hearing Loss: Delivery of Insulin-Like Growth Factor 1 to the Cochlea Using Gelatin Hydrogel

Lee, Kyu Yup*‡; Nakagawa, Takayuki*; Okano, Takayuki*; Hori, Ryusuke*; Ono, Kazuya*; Tabata, Yasuhiko; Lee, Sang Heun; Ito, Juichi*

doi: 10.1097/MAO.0b013e31811f40db
Basic Science
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Hypothesis: Local application of recombinant human insulin-like growth factor 1 (rhIGF-1) via a biodegradable hydrogel after onset of noise-induced hearing loss (NIHL) can attenuate functional and histologic damage.

Background: The biodegradable gelatin hydrogel makes a complex with drugs by static electric charges and releases drugs by degradation of gelatin polymers. We previously demonstrated the efficacy of local rhIGF-1 application via hydrogels before noise exposure for prevention of NIHL.

Methods: First, we used an enzyme-linked immunosorbent assay to measure human IGF-1 concentrations in the cochlear fluid after placing a hydrogel containing rhIGF-1 onto the round window membrane of guinea pigs. Second, the functionality and the histology of guinea pig cochleae treated with local rhIGF-1 application at different concentrations after noise exposure were examined. Control animals were treated with a hydrogel immersed in physiologic saline alone.

Results: The results revealed sustained delivery of rhIGF-1 into the cochlear fluid via the hydrogel. The measurement of auditory brainstem responses demonstrated that local rhIGF-1 treatment significantly reduced the threshold elevation from noise. Histologic analysis exhibited increased survival of outer hair cells by local rhIGF-1 application through the hydrogel.

Conclusion: These findings indicate that local rhIGF-1 treatment via gelatin hydrogels is effective for treatment of NIHL.

*Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, and †Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan; and ‡Department of Otolaryngology, Kyungpook National University Hospital, Daegu, Korea

Address correspondence and reprint requests to Takayuki Nakagawa, M.D., Ph.D., Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo-ku, 606-8507 Kyoto, Japan; E-mail: tnakagawa@ent.kuhp.kyoto-u.ac.jp

This study was supported by a grant-in-aid for Regenerative Medicine Realization Project from the Ministry of Education, Science, Sports, Culture, and Technology of Japan and by a grant-in-aid for Researches on Sensory and Communicative Disorders from the Japanese Ministry of Health, Labor, and Welfare.

© 2007 Otology & Neurotology, Inc.