Towards the development of a "living" cochlear implant

描述（由申请人提供）：耳蜗毛细胞及其提供的内源性营养支持的丧失导致听觉神经元变性，可导致连续的听力障碍。越来越多的证据表明，神经营养药物治疗，如脑源性神经营养因子（BDNF），足以维持毛细胞丢失后听觉神经元的存活。然而，与未经治疗的耳蜗相比，停止神经营养因子治疗可能导致神经元丢失加速。因此，寻找一种将神经营养剂长期输送到病变耳的听觉神经元的方法是至关重要的。传统的分娩策略，通常与人工耳蜗植入分离，作为患病耳朵的临床治疗，存在许多问题，包括分娩轮廓不均匀，时间有限，以及难以取出。因此，该项目的总体目标是开发一种“活体”人工耳蜗，该人工耳蜗结合了基于组织工程概念的长期、持续和靶向治疗药物递送策略。具体来说，人工耳蜗与活的神经营养因子释放细胞结合，将在本项目中评估神经营养因子的长期递送。在项目过程中，将实现两个具体目标。特异性目的1是确定体外植入物的神经营养因子释放谱。具体目的2是在动物模型中评估植入物预防继发性毛细胞丢失的神经变性的治疗效果。拟建工程将于两年内完成。该项目的完成将为听力受损患者提供临床适用的生物医学设备，这些设备具有当前病变耳部治疗的所有优点，但更有效，并为听力受损患者在不同疾病阶段的治疗选择提供更大的灵活性。此外，该项目将为将工程原理融入生命科学和医学建立指导方针，从而有利于听觉功能恢复和生物工程的研究领域。这些指南将加强对疾病的治疗，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为耳聋患者提供临床适用的生物医学设备，这些设备具有当前病耳治疗的所有优点，并且在疾病的不同阶段提供更有效和更灵活的治疗选择。

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.