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）： 建议：需要支持改进人工耳蜗或人工耳蜗。人工耳蜗植入物采用电刺激来激活由于内耳感觉细胞死亡而失去听力的患者的听觉神经元。这种设备现在被广泛用于治疗聋人，并且越来越多地用于患有 残余听力它为这两个人群提供了实质性的益处，但即使是最成功的患者的表现也远远低于正常听力者的表现。该研究计划旨在通过结合器件工程和生物学方法来改进人工耳蜗。研究设计：通过减少电极和耳蜗神经元之间的距离，从而可以传递更多的信息通道，通过增加耳蜗神经元的存活率，以及通过保持神经元与植入物接触，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。该计划的先前研究主要使用体外方法来确定调节耳蜗神经纤维生长和增强神经元存活的因素;通过可能将耳蜗植入物连接到螺旋神经节区域的三维基底来评估神经突的生长，并评估植入材料上内耳神经纤维的生长。在本申请中，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。这包括有效性和材料相容性研究，探索促进螺旋神经节神经纤维生长的技术，以及评估钛作为稳定的神经元附着和存活介质。方法学：通过应用耳毒素对豚鼠进行麻醉。然后，他们将被植入耳蜗植入物，植入物被水凝胶包围，其中微通道被设计成从耳蜗神经节通向植入物。渗透微型泵，细胞工程产生神经营养因子，和介导神经营养因子缓慢释放的层层薄膜，将被用来吸引耳蜗神经元纤维进入微通道和植入物。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，通常是由于服役和部署造成的耳朵损伤。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。将在本计划中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界面也可以应用于视觉缺陷和脊髓损伤的退伍军人。