Growth factor-eluting cochlear implant electrode: impact on residual auditory function, insertional trauma, and fibrosis

Journal of Translational Medicine

Juichi Ito³  Akio Ido⁴  Hirohito Tsubouchi⁴  Yasuhiko Tabata²  Lin Ying¹  Takayuki Nakagawa³  Yayoi S Kikkawa³ 

[1]Department of Otolaryngology and Head and Neck Surgery, Xijing Hospital, Xi¿an, China

[2]Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Science, Kyoto University, Kyoto, Japan

[3]Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kawaharacho 54, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

[4]Department of Digestive and Life-style Related Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan

关键词: Insertional trauma;    Hearing loss;    Guinea pig;    Hepatocyte growth factor (HGF);    Insulin-like growth factor 1 (IGF1);    Spiral ganglion neuron;    Auditory hair cells;    Gelatin hydrogel;    Drug delivery system;    Cochlear implant;   

Others  :  1147699
DOI  :  10.1186/s12967-014-0280-4

 received in 2014-04-30, accepted in 2014-09-24,  发布年份 2014

【 摘 要 】

Background

A cochlear implant (CI) is an artificial hearing device that can replace a damaged cochlea. The present study examined the use of growth factor-eluting gelatin hydrogel coatings on the electrodes to minimize inner ear trauma during electrode insertion. Insulin-like growth factor 1 (IGF1) and/or hepatocyte growth factor (HGF) were chosen as the agents to be administered.

Methods

Silicone CI electrode analogs were prepared and coated with gelatin hydrogels. Adsorption/release profile of the hydrogel was measured using ¹²⁵I-radiolabeled IGF. Hydrogel-coated electrodes were absorbed with IGF1, HGF, IGF1 plus HGF, or saline (control) and implanted into the basal turns of guinea pig cochleae (n?=?5). Auditory sensitivity was determined pre-operatively, immediately after, and 3, 7, 14, 21, and 28 days post-operatively by using auditory brainstem response (ABR; 4¿16 kHz). In addition, histological analysis was performed and auditory hair cell (HC) survival, spiral ganglion neuron (SGN) densities, and fibrous tissue thickness were measured.

Results

Compared to non-coated arrays, hydrogel-coated electrodes adsorbed significantly greater amounts of IGF1 and continuously released it for 48 h. Residual hearing measured by ABR thresholds after surgery were elevated by 50¿70 dB in all of the electrode-implanted animals, and was maximal immediately after operation. Thresholds were less elevated after hydrogel treatment, and the hearing protection improved when IGF1 or HGF was applied. Histopathologically, hair cell survival, spiral ganglion cell survival, and fibrous tissue thickness were not different between the experimental groups. No serious adverse events were observed during the 4-week observation period.

Conclusions

Our findings provide the first evidence that hydrogel-coated, growth factor-releasing CI electrodes could attenuate insertional trauma and promote recovery from it, suggesting that this combination might be a new drug delivery strategy not only in cochlear implantation but also in treating clinical conditions characterized by inner ear damage.

【 授权许可】

   
2014 Kikkawa et al.; licensee BioMed Central Ltd.

【 图 表 】

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