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：要求提供对人工耳蜗假体或人工耳蜗植入物的改进的支持。人工耳蜗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。该设备现在被广泛用于治疗聋人，越来越多地用于 残留听力。它为两个人群都提供了可观的好处，但是即使是最成功的患者的表现远低于正常听众听众所获得的。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善人工耳蜗植入物。研究设计：通过降低电极和耳蜗神经元之间的距离，可以提高性能，从而通过增加耳蜗神经元的存活以及维持与植入物接触的神经元的生存，可以传递更多的信息渠道。这些目标将通过在植入物和内耳组织之间产生生物学接口来实现。该程序的先前研究主要使用体外方法来识别调节人工耳蜗生长并增强神经元存活的因素。通过三维底物评估神经突的生长，这些底物可能将人工耳蜗植入物与螺旋神经节区域联系起来，并评估内耳神经纤维在植入物材料上的生长。在此应用中，我们建议使用完全感觉细胞损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，探索螺旋神经节中神经纤维生长的技术以及将钛作为稳定的神经元附着和生存培养基的评估。方法论：豚鼠将通过施用耳毒素聋。然后，它们将与被水凝胶包围的人工耳蜗植入，其中已设计了微通道从耳蜗神经节到植入物。渗透微型蛋白酶，设计用于产生神经营养蛋白的细胞以及介导神经营养蛋白缓慢释放的逐层薄膜，可用于吸引人工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的神经纤维并增强其存活率。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，通常是由于兵役和部署而导致耳朵造成的。未来的研究将包括对人体组织的实验，临床装置的开发和临床试验。该计划中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界面也可以应用于具有视觉缺陷和脊髓损伤的退伍军人。