Gapless man: machine interface in the inner ear

世界人口的5%以上，即3.6亿人患有致残性听力损失。在严重的情况下，听觉功能可以通过一种叫做人工耳蜗（cochlear implant，简称CI）的神经假体来恢复。人工耳蜗通过直接刺激听觉神经纤维，在功能上取代失去的内耳感觉细胞。尽管这些装置取得了成功，但仍然存在一些局限性，包括听觉分辨率不理想和能量消耗高，这主要是由于耳蜗内植入的电极阵列与附近的听觉神经元之间存在解剖间隙。在最近完成的一个由主要申请人（www.nanoci.org）协调的多国欧盟FP7项目中，通过引导听神经纤维向电极阵列生长来克服解剖间隙的原理证明已经在体内获得。此外，体外实验表明，如果消除听觉神经元与电极的距离，刺激能量可能会减少5倍。在该项目中，我们打算通过优化生长因子引导，结合慢性电刺激，以及体外和体内再生听觉神经元的详细形态学、生化和电生理特征，来改善无间隙界面。天然和干细胞生成，捐赠的人类听觉神经元将用于体外验证。该项目的最终目标是通过体内慢性电刺激来评估听觉神经元与人工耳蜗电极之间无间隙界面的潜力。如果成功，该项目可能会导致更节能的人工耳蜗植入系统，具有更高的听觉分辨率和改善的音质。

Over 5% of the world population, 360 Million people, suffer from disabling hearing loss. In severe forms, the auditory function can be restored by a neuroprostheses called a cochlear implant (CI), which functionally replaces lost inner ear sensory cells by directly stimulating the auditory nerve fibers. Despite the success of these devices, some limitations remain, including suboptimal auditory resolution and high energy consumption, which are mainly due to the anatomical gap between the implanted electrode array in the cochlea and the auditory neurons nearby. Within a recently completed, multinational EU FP7 project coordinated by the main applicant (www.nanoci.org), proof of principle for overcoming the anatomical gap by guided growth of auditory nerve fibers towards the electrode array has been obtained in vivo. In addition, in vitro experiments have shown a potential reduction of the stimulus energy by a factor of 5, if the distance of the auditory neurons from the electrode was eliminated. Within the proposed project, we intend to improve the gapless interface through optimized growth factor guidance in combination with chronic electrical stimulation and detailed morphological, biochemical and electrophysiological characterization of regrown auditory neurons in vitro and in vivo. Native and stem cell generated, donated human auditory neurons will be used in vitro for validation. The ultimate goal of the proposed project is to assess the potential of the gapless interface between auditory neurons and the cochlear implant electrodes through chronic electrical stimulation in vivo. If successful, the proposed project may lead to more energy efficient cochlear implant systems with higher auditory resolution and improved sound quality.