Towards the development of a "living" cochlear implant

致力于开发“活的”人工耳蜗

• 批准号: 7328415
• 负责人: XUEJUN WEN
• 金额: $ 18.38万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7328415
• 关键词: Acoustic Nerve; Animal Model; Area; Auditory; Auditory system; Biological Sciences; Biomedical Engineering; Brain-Derived Neurotrophic Factor; Calibration; Catheters; Cell Count; Cells; Clinical; Clinical Treatment; Cochlea; Cochlear Implants; Cochlear implant procedure; Collaborations; Culture Media; Data; Development; Devices; Disease; Ear; Electrophysiology (science); Encapsulated; Engineering; Enzyme-Linked Immunosorbent Assay; Fiber; Figs - dietary; Future; Generations; Gerbils; Goals; Guidelines; Hair Cells; Hearing; Hearing Impaired Persons; Histology; Impairment; Implant; In Vitro; Industry; Interdisciplinary Study; Laboratories; Labyrinth; Lead; Life; Measures; Medicine; Membrane; Molecular Weight; Natural regeneration; Neomycin; Nerve Degeneration; Nerve Fibers; Neurons; Numbers; Patients; Peripheral; Pharmaceutical Preparations; Pliability; Positioning Attribute; Proliferating; Pump; Regenerative Medicine; Research; Retrieval; Scientist; Secondary to; Staging; Surgeon; Testing; Therapeutic Agents; Tissue Engineering; Tissues; Translating; Treatment Efficacy; Weight maintenance regimen; Western Blotting; afferent nerve; auditory nuclei; base; biodegradable polymer; biomaterial compatibility; career; concept; controlled release; design; functional restoration; hearing impairment; immunocytochemistry; implantation; in vivo; neurogenesis; neuron loss; neurotrophic factor; next generation; novel; prevent; scaffold; targeted delivery

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.

描述（由申请人提供）：由于耳蜗细胞的丧失和内源性的营养支持，听觉神经元的退化会导致连续的听力障碍。越来越多的证据表明，用神经营养剂（例如脑衍生的神经营养因子（BDNF））进行治疗足以维持毛细胞丧失后听觉神经元的存活。然而，与未经处理的耳蜗相比，神经营养蛋白治疗的停止可能导致神经元丧失。因此，找到一种长期递送神经营养剂向患病耳朵中听觉神经元的方法是必不可少的。常规的分娩策略通常与人工耳蜗植入作为患病耳朵的临床治疗方法，遇到了许多问题，包括不均匀的交付概况，有限的时间递送概况以及检索难度。因此，该项目的总体目标是开发一种“活着的”人工耳蜗，该植入物结合了基于组织工程概念的长期，持续和有针对性的治疗性交付策略。具体而言，将在该项目中评估一种与活神经营养细胞结合的人工耳蜗植入物，用于长期递送神经营养蛋白。在项目过程中将实现两个具体目标。具体目的1是定义体外植入物的神经营养释放曲线。具体目的2是评估植入物在预防动物模型中发胶损失的神经变性方面的治疗功效。拟议的项目将在两年内完成。实现该项目将通过提供临床适用的生物医学设备，直接受到听力障碍患者的影响，这些设备具有当前治疗疾病耳朵治疗的所有优点，但更有效，并为在不同疾病的不同阶段的听力受损患者提供了更大的灵活性。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南，从而使听觉功能恢复和生物工程的研究领域受益。这些准则将增强对疾病的治疗，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。该项目的成功实现将直接使聋哑患者提供临床适用的生物医学设备，这些设备具有当前患病耳朵治疗的所有优点，但更有效，并且在疾病不同阶段的治疗方案中提供了更大的灵活性。