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

Journal of translational medicine (2014-10-05)
Yayoi S Kikkawa, Takayuki Nakagawa, Lin Ying, Yasuhiko Tabata, Hirohito Tsubouchi, Akio Ido, Juichi Ito
ABSTRACT

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. Silicone CI electrode analogs were prepared and coated with gelatin hydrogels. Adsorption/release profile of the hydrogel was measured using (125)I-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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

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HGF human, recombinant, expressed in CHO cells, ≥97% (SDS-PAGE), ≥97% (HPLC)
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Hepatocyte Growth Factor human, HGF, recombinant, expressed in HEK 293 cells, HumanKine®, suitable for cell culture
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Hepatocyte Growth Factor human, HGF, recombinant, expressed in NSO cells, suitable for cell culture
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Hematoxylin, certified by the Biological Stain Commission
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Hematoxylin
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Sodium iodide, AnhydroBeads, −10 mesh, 99.999% trace metals basis
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Sodium iodide, 99.999% trace metals basis
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HGF human, recombinant, expressed in HEK 293 cells, ≥95% (SDS-PAGE)
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