A Biological Interface for Auditory Rehabilitation with a Cochlear Implant

描述(由申请人提供)： 目的：为改进人工耳蜗术或人工耳蜗术的发展提供支持。人工耳蜗植入物使用电刺激来激活因内耳感觉细胞死亡而失去听力的患者的听神经元。这种设备现在被广泛用于治疗聋人，并越来越多地用于患有耳聋的患者 剩余的听力。它为这两个群体提供了实质性的好处，但即使是最成功的患者的表现也远远低于正常听力听者的表现。拟议的研究计划旨在通过将设备工程和生物学方法相结合来改进人工耳蜗。研究设计：通过减小电极和耳蜗神经元之间的距离，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的接触，可以提高性能，从而可以传递更多的信息。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。该项目的前期研究主要采用体外方法，确定调节耳蜗神经纤维生长和提高神经元存活的因素；通过可能将人工耳蜗体连接到螺旋神经节区域的三维基质来评估神经突起的生长；以及评估植入材料上内耳神经纤维的生长。在这个应用中，我们建议使用完全感觉细胞丧失的动物模型，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，探索促进螺旋神经节外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生存介质。方法：应用耳毒素致聋豚鼠。然后，他们将被植入被水凝胶包围的人工耳蜗体，在水凝胶中，微通道被设计成从耳蜗神经节引导到植入物。渗透性微泵是一种制造神经营养因子的细胞，以及一层又一层的薄膜，它们介导神经营养因子的缓慢释放，将被用来吸引耳蜗神经纤维进入微通道和植入物。表面工程钛将用于维持植入物上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。本课程将研究的一般原则也将适用于退伍军人的其他健康问题。改进的电极阵列和神经元之间的接口也可以应用于视力障碍的退伍军人和脊髓损伤。

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.