Towards the development of a "living" cochlear implant

描述(由申请人提供)：由于耳蜗毛细胞和内源性营养支持的丧失而导致的听神经元退化可导致继发性听力损伤。越来越多的证据表明，使用脑源性神经营养因子(BDNF)等神经营养剂治疗足以维持毛细胞丧失后听神经元的存活。然而，与未治疗的耳蜗相比，停止神经营养素治疗可能会导致神经元加速丢失。因此，找到一种将神经营养剂长期输送到患病耳朵中的听神经元的方法是至关重要的。作为耳部疾病的一种临床治疗方法，传统的给药策略通常与人工耳蜗植入相分离，但存在许多问题，包括给药曲线不均匀，时间给药曲线有限，以及检索困难。因此，该项目的总体目标是开发一种“活的”人工耳蜗，它结合了基于组织工程学概念的长期、持续和有针对性的治疗药物输送策略。具体地说，在这个项目中，将评估一种与活的神经营养因子释放细胞相结合的人工耳蜗，以实现神经营养因子的长期输送。在项目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谱。具体目的2是评价该植入物在动物模型中预防继发于毛细胞丢失的神经变性的治疗效果。拟议的项目将在两年内完成。该项目的实施将直接使听力障碍患者受益，因为它提供了临床适用的生物医学设备，这些设备具有目前治疗耳部疾病的所有优点，但更有效，并为处于不同疾病阶段的听力障碍患者提供了更灵活的治疗选择。此外，拟议的项目将通过建立将工程原理纳入生命科学和医学的指导方针，使听觉功能恢复和生物工程的研究领域普遍受益。这些指南将加强疾病的治疗，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。这一项目的成功实施将使聋人患者直接受益，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耳疾的所有优点，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.