Towards the development of a "living" cochlear implant

描述（由申请人提供）：由于耳蜗毛细胞及其提供的内源性营养支持的丧失而导致的听觉神经元退化可导致连续性听力损伤。越来越多的证据表明，治疗与神经营养剂，如脑源性神经营养因子（BDNF），足以维持听觉神经元的存活后，损失的毛细胞。然而，与未治疗的耳蜗相比，停止神经营养因子治疗可能导致加速的神经元损失。因此，找到一种方法，长期提供神经营养剂的听觉神经元在患病的耳朵是必不可少的。常规的递送策略通常与作为患病耳朵的临床治疗的耳蜗植入分离，具有许多问题，包括不均匀的递送轮廓、有限的时间递送轮廓以及难以取回。因此，该项目的总体目标是开发一种“活”人工耳蜗植入体，该人工耳蜗植入体基于组织工程概念，采用长期、持续和有针对性的治疗剂输送策略。具体而言，将在该项目中评价与活的神经营养素释放细胞组合的耳蜗植入物用于长期递送神经营养素。在项目实施过程中将实现两个具体目标。具体目标1是确定植入物在体外的神经营养素释放概况。具体目标2是在动物模型中评价植入物在预防继发于毛细胞损失的神经变性方面的疗效。拟议的项目将在两年内完成。该项目的实施将通过提供临床适用的生物医学设备直接受益于听障患者，这些设备具有目前治疗病耳的所有优点，但更有效，并为听障患者在疾病的不同阶段提供更灵活的治疗选择。此外，拟议的项目将有利于听觉功能恢复和生物工程的研究领域，通过建立将工程原理纳入生命科学和医学的指导方针。这些指南将加强疾病治疗并促进工程师、生物学家和临床外科医生之间的多学科合作。该项目的成功实施将直接使耳聋患者受益，为他们提供临床适用的生物医学设备，这些设备具有目前治疗病耳的所有优点，但更有效，并在疾病的不同阶段提供更灵活的治疗选择。

DESCRIPTION (provided by applicant): Degeneration of auditory neurons due to the loss of cochlear hair cells and endogenous trophic support they provide can lead to successive hearing impairments. Growing evidence indicates that treatment with neurotrophic agents, such as brain-derived neurotrophic factor (BDNF), is sufficient to maintain survival of auditory neurons after loss of hair cells. However, cessation of neurotrophin treatment may result in accelerated neuronal loss compared to untreated cochleas. Therefore, finding a means of long-term delivery of neurotrophic agents to auditory neurons in the diseased ear is essential. Conventional delivery strategies, often separated from cochlear implantation as a clinical treatment for the diseased ear, come with numerous problems, including uneven delivery profiles, limited temporal delivery profiles, and difficulty with retrieval. Therefore, the overall objective of this project is to develop a "living" cochlear implant that incorporates long-term, sustained, and targeted therapeutic-agent delivery strategies based on a tissue-engineering concept. Specifically, a cochlear implant combined with living neurotrophin- releasing cells, will be evaluated in this project for long-term delivery of neurotrophins. Two specific aims will be achieved during the course of the project. Specific Aim 1 is to define the neurotrophin-releasing profiles of the implant in vitro. Specific Aim 2 is to evaluate the therapeutic efficacy of the implant in preventing nerve degeneration secondary to hair-cell loss in animal models. The proposed project will be completed in two years. Fulfillment of this project will directly benefit hearing-impaired patients by providing clinically applicable biomedical devices that possess all the merits of current treatments for the diseased ear yet are more efficacious and provide more flexibility in treatment options for hearing-impaired patients at different stages of disease. In addition, the proposed project will benefit the research fields of auditory functional restoration and bioengineering in general by establishing guidelines for incorporating engineering principles into life science and medicine. These guidelines will enhance therapy for diseases and promote multidisciplinary collaborations among engineers, biologists, and clinical surgeons. Successful fulfillment of this project will directly benefit deaf patients by providing them with clinically applicable biomedical devices that possess all the merits of current treatments for the diseased ear yet are more efficacious and provide more flexibility in the treatment options at different stages of the diseases.