Living electrodes for auditory rehabilitation.

听力损失影响着2800多万美国人，是退伍军人的第二大常见残疾 人口。由于听力损失太严重，助听器无法帮助听力损失，人工耳蜗术已成为 护理的标准。尽管它们可以恢复许多人理解语音的能力，但目前的电极具有 对神经元兴奋的选择性较差。这限制了保真度，导致难以处理背景噪音、 电话，还有音乐欣赏。神经创伤、神经退行性变和 CMC-VAMC的修复(CNNR)开创了基于生物的神经与神经元的接口- 尚未应用于听力恢复的特定刺激。这个项目利用了可移植的生活方式 通过生物杂交神经接口进行听力康复的支架。 将开发生物混合神经接口，允许移植的螺旋神经节神经元(SGN)保留 当轴突与中枢听觉通路或耳蜗神经元相互作用时，可获得刺激- 创造出一种“活电极”。SGN将从新生大鼠的颞骨中获得，细胞的能力 刺激不同群体的SGN(人工耳蜗植入)和中枢衍生神经元(脑干 植入)将在培养中得到确认。光激活的视蛋白也将被诱导以允许光学 刺激。然后，在体外，将在两种不同的支架上生长SGN。第一个引导移植的SGN轴突 到脑干的下丘，第二个将它们从耳蜗圆的窗口引导到 原生螺旋神经节。这两种设计都允许对移植的SGN细胞进行电和光刺激 身体。一旦被移植到活体大鼠体内，细胞的存活和整合情况就会被评估 免疫组织化学在不同的时间点长达6个月。来自听觉的电生理记录 在耳聋大鼠体内植入脑干或耳蜗支架后，将获得皮质，同时 电刺激或光刺激的。然后将使用行为模型来评估听觉感知 通过刺激活的脚手架诱导的。 该项目的最终产品将是用于听力康复的两种形式的活电极，其中一种用于 一枚植入下丘，一枚植入耳蜗内。预计神经元- 这项技术允许的特定模拟将允许在刺激听觉系统时的精确度 这是目前的植入技术无法接近的。 这是一项新提案的重新提交。 这项工作可以直接翻译成改进的植入式听力装置，也适用于听力损失的人 使用传统助听器进行充分康复是非常困难的。儿童康复方案的改进 这些退伍军人将对他们的生活质量和福祉产生重大影响。 这项拟议的工作不仅推进了下一代基于生物的接口，以恢复这种能力 为了解释我们退伍军人的复杂听觉输入，作为职业发展奖，它还将作为 扩展我在组织工程和再生疗法方面的技术技能的工具。这一CDA将形成 在推动听力恢复的界限方面奠定了职业基础。

Hearing loss affects over 28 million Americans and is the second most common disability in the Veteran population. For hearing loss too severe to be helped by hearing aids, cochlear implants have become the standard of care. Though they can restore the ability to understand speech for many, current electrodes have poor selectivity for neuronal excitation. This limits fidelity leading to difficulty with background noise, talking on the phone, and music appreciation. Researchers at the Center for Neurotrauma, Neurodegeneration, and Restoration (CNNR) at the CMC-VAMC have pioneered biologically-based neural interfaces with neuron- specific stimulation that have yet to be applied to hearing restoration. This project utilizes transplantable living scaffolds for the rehabilitation of hearing through biohybrid neural interfaces. Biohybrid neural interfaces will be developed that allow transplanted spiral ganglion neurons (SGN) to remain accessible to stimulation while their axons interact with neurons of the central auditory pathway or cochlea – creating a “living electrode”. SGN will be harvested from neonatal rat temporal bones and the cells’ ability to stimulate a distinct population of SGN (cochlear implantation), and centrally derived neurons (brainstem implantation) will be confirmed in culture. Light activated opsins will also be induced to allow for optical stimulation. SGNs will then be grown on two distinct scaffolds in vitro. The first directs transplanted SGN axons to the inferior colliculus in the brainstem, and the second directs them from the round window of the cochlea to the native spiral ganglion. Both designs allow for electric and optical stimulation of the transplanted SGN cell bodies. Once transplanted into living rats, cell survival and integration are evaluated with immunohistochemistry at various timepoints for up to 6 months. Electrophysiologic recordings from the auditory cortex will be obtained in deafened rats implanted with either the brainstem or cochlear scaffolds, while being stimulated either electrically or optically. Behavioral models will then used to evaluate the auditory perception induced via stimulation of the living scaffolds. The final product of this project will be two form-factors of living electrodes for hearing rehabilitation, one for implantation into the inferior colliculus and one for implantation into the cochlea. It is expected that the neuron- specific simulation permitted by this technique will allow for precision in stimulation of the auditory system that cannot be approached by current implant technology. This is a resubmission of a new proposal. This work is directly translatable to improved implantable hearing devices for those with hearing loss too severe to be adequately rehabilitated with traditional hearing aids. Improvement in the rehabilitative options for these veterans will have a significant impact on their quality of life and well-being. Not only does the proposed work advance a next generation, biologically based interface to restore the ability to interpret sophisticated auditory inputs in our Veterans, as a Career Development Award, it will also serve as vehicle to expand my technical skills in tissue engineering and regenerative therapies. This CDA will form the foundation of a career in pushing the boundaries of hearing restoration.