Abstract
BackgroundA 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.MethodsSilicone 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.ResultsCompared 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.ConclusionsOur 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.
Highlights
A cochlear implant (CI) is an artificial hearing device that can replace a damaged cochlea
We have developed insulin-like growth factor 1 (IGF1)and hepatocyte growth factor (HGF)-containing hydrogels [13] and conducted a series of animal experiments, which revealed that topical growth factor application via gelatin hydrogels significantly improved hearing by protecting auditory hair cells (HCs) against damage caused by intense noise exposure [14,15], drug-induced hearing loss [16], or ischemic injury [17], with no adverse events
Adsorption and release profile of Insulin-like growth factor 1 (IGF1) from hydrogel-coated electrodes First, we evaluated the adsorption of IGF1 to the synthesized electrodes by radioactivity assay, i.e., measuring relative intensities of radioactivity on the electrodes after they were immersed in 125I-labeled IGF1 solution for 1 h
Summary
A cochlear implant (CI) is an artificial hearing device that can replace a damaged cochlea. Recent advances in CI technology have led to the development of a new generation of hearing-preserving CIs with less traumatic electrodes that minimize inner ear trauma during electrode insertion. This is true for those with some residual hearing who may benefit from newly emerging stimulus strategies that employ a combination of electrical and acoustic stimulation. Even with the introduction of minimally traumatic “soft” surgical techniques (reviewed in [5] and [6]) and electrodes that have been modified to reduce intracochlear trauma during their insertion [7], residual hearing is lost or incompletely preserved in one-third of cases [8]. Some researchers have begun to explore the possibility that better hearing preservation may be achieved by the application of protective pharmacological agents to the inner ear at the time of surgery ([9,10] and [11], reviewed in [6])
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