A Biological Interface for Auditory Rehabilitation with a Cochlear Implant

人工耳蜗听力康复的生物接口

• 批准号: 8594549
• 负责人: Allen F. Ryan
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8594549
• 关键词: Adult; Animal Model; Animals; Auditory; Biocompatible Materials; Biological; Blast Cell; Cavia; Cells; Cessation of life; Clinical; Clinical Trials; Cochlea; Cochlear Implants; Cochlear Nerve; Development; Device or Instrument Development; Devices; Ear; Electric Stimulation; Electrodes; Engineering; Equilibrium; Evaluation; Exposure to; Fiber; Film; Future; Ganglia; Goals; Growth; Growth Factor; Health; Hearing; Hearing Impaired Persons; Hearing problem; High-Frequency Hearing Loss; Human Resources; Hydrogels; Implant; In Vitro; Labyrinth; Lead; Link; Mediating; Methods; Middle East; Military Personnel; Nature; Nerve Fibers; Neurites; Neurons; Noise; Patients; Performance; Population; Process; Prostheses and Implants; Rehabilitation therapy; Research; Residual state; Risk; Safety; Scala Tympani; Sensorineural Hearing Loss; Sensory; Services; Signal Transduction; Spinal cord injury; Surface; Techniques; Tinnitus; Tissues; Titania; Titanium; Veterans; Visual; cellular engineering; cost; design; disability; disability payment; ear infection; equilibration disorder; hearing impairment; human subject; human tissue; implant material; improved; in vivo; middle ear; neurite growth; neuronal survival; neurotrophic factor; osmotic minipump; ototoxin; programs; public health relevance; research study; spiral ganglion

DESCRIPTION (provided by applicant): OBJECTIVES: Support is requested for the development of improvements to the cochlear prosthesis or cochlear implant. The cochlear implant employs electrical stimulation to activate auditory neurons in patients that have lost their hearing due to the death of inner ear sensory cells. This device is now widely used to treat the deaf, and is increasingly used for patients with residual hearing. It provides substantial benefit for both populations, but the performance of even the most successful patients is far lower than that achieved by normal hearing listeners. The proposed research program is designed to improve the cochlear implant by combining device engineering and biological approaches. RESEARCH DESIGN: Performance will be enhanced by decreasing the distance between the electrodes and cochlear neurons, so that more channels of information can be delivered, by increasing the survival of cochlear neurons, and by maintaining the neurons in contact with the implant. These goals will be achieved by producing a biological interface between the implant and the tissues of the inner ear. The prior research of this program has used primarily in vitro methods to identify factors that regulate the growth of cochlear nerve fibers and enhance neuronal survival; to evaluate the growth of neurites through three-dimensional substrates that might link a cochlear implant to the region of the spiral ganglion, and to evaluate the growth of inner ear nerve fibers on implant materials. In this application, we propose to transfer these in vitro results to the in vivo situation, using an animal model of complete sensory cell loss. This includes efficacy and materials compatibility studies, exploration of techniques to enhance growth of nerve fibers out of the spiral ganglion, and evaluation of titanium as a stable neuronal attachment and survival medium. METHODOLOGY: Guinea pigs will be deafened by the application of ototoxins. They will then be implanted with cochlear implants surrounded by hydrogels in which microchannels have been engineered to lead from the cochlear ganglion to the implant. Osmotic minipumps, cells engineered to produce neurotrophins, and layer-by-layer thin films that mediate slow release of neurotrophins, will be used to attract cochlear neuron fibers into the microchannels and to the implant. Surface engineered titanium will be used to maintain nerve fibers at the implant and enhance their survival. CLINICAL RELATIONSHIP: Disorders of hearing and balance, including SNHL, tinnitus, balance disorders and middle ear infections, are major health problems for Veterans, often resulting from damage to the ear as a consequence of military service and deployment. Future studies will include experiments with human tissue, development of a clinical device, and clinical trials. The general principles that will be studied in this program wll also be applicable to other health problems of Veterans. Improved interfaces between electrode arrays and neurons could also be applied to Veterans with visual deficits and in spinal cord injury.

描述（由申请人提供）： 目标：请求支持开发人工耳蜗或人工耳蜗的改进。人工耳蜗采用电刺激来激活因内耳感觉细胞死亡而丧失听力的患者的听觉神经元。该设备现已广泛用于治疗聋哑人，并且越来越多地用于患有以下疾病的患者： 残余听力。它为这两个人群提供了巨大的好处，但即使是最成功的患者的表现也远远低于正常听力听众所达到的表现。拟议的研究计划旨在通过结合设备工程和生物学方法来改进人工耳蜗。研究设计：通过缩短电极和耳蜗神经元之间的距离，从而可以传递更多信息通道，增加耳蜗神经元的存活率，并保持神经元与植入物的接触，可以提高性能。这些目标将通过在植入物和内耳组织之间产生生物界面来实现。该项目之前的研究主要使用体外方法来识别调节耳蜗神经纤维生长和增强神经元存活的因素；通过可能将人工耳蜗植入物与螺旋神经节区域连接起来的三维基底评估神经突的生长，并评估植入材料上内耳神经纤维的生长。在此应用中，我们建议使用感觉细胞完全丧失的动物模型将这些体外结果转移到体内情况。这包括功效和材料兼容性研究、探索增强螺旋神经节神经纤维生长的技术，以及评估钛作为稳定神经元附着和生存介质的作用。方法：使用耳毒素会使豚鼠失聪。然后，他们将被植入被水凝胶包围的耳蜗植入物，其中的微通道被设计成从耳蜗神经节通向植入物。渗透微型泵、被设计用于产生神经营养素的细胞以及介导神经营养素缓慢释放的逐层薄膜将用于将耳蜗神经元纤维吸引到微通道和植入物中。表面工程钛将用于维持植入物处的神经纤维并提高其存活率。临床关系：听力和平衡障碍，包括 SNHL、耳鸣、平衡障碍和中耳感染，是退伍军人的主要健康问题，通常是由于服兵役和部署造成的耳朵损伤造成的。未来的研究将包括人体组织实验、临床设备的开发和临床试验。该计划将研究的一般原则也适用于退伍军人的其他健康问题。电极阵列和神经元之间的改进接口也可以应用于患有视力缺陷和脊髓损伤的退伍军人。