Local application of hepatocyte growth factor using gelatin hydrogels attenuates noise-induced hearing loss in guinea pigs

Takatoshi Inaokaa, Takayuki Nakagawa PhD MDa*, Yayoi S. Kikkawaa, Yasuhiko Tabatab, Kazuya Onoa, Mitsuhiro Yoshidaa, Hirohito Tsubouchic, Akio Idoc & Juichi Itoaa Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicineb Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Science, Kyoto University, Kyotoc Department of Digestive and Life-style Related Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan† Correspondence: Takayuki Nakagawa, Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan, +81 75 751 3346, +81 75 751 7225 tnakagawa@ent.kuhp.kyoto-u.ac.jpConclusion: Local application of hepatocyte growth factor using biodegradable gelatin hydrogels attenuates noise-induced hearing loss in guinea pigs. Objectives: To develop an inner ear drug delivery system using gelatin hydrogels that is capable of a sustained delivery of growth factors to the cochlea. We examined the efficacy of the local application of gelatin hydrogels containing hepatocyte growth factor (HGF) in protecting cochlear hair cells from noise-induced damage. Materials and methods: A piece of gelatin hydrogel previously immersed in either HGF or saline was placed on the round window membrane of a guinea pig 1 h after noise exposure (4 kHz octave band noise at 120 dB sound pressure level for 3 h). Auditory function was monitored using auditory brainstem responses (ABRs), and the loss of hair cells was evaluated quantitatively. Results: Local HGF treatment significantly reduced the noise exposure-caused ABR threshold shifts and the loss of outer hair cells in the basal portion of the cochleae.