Optimization, Biocompatibility and Safety Assessment of Tongue Implants

描述(由申请人提供)：高度脊髓损伤(SCI)患者对其环境的辅助控制选择有限，部分原因是患者意志运动系统的计算机接口的信号多样性有限。舌头是一种能够在自愿控制下执行各种运动的运动系统，在高度SCI的患者中是不存在的，因此是四肢瘫痪患者进行计算机接口的天然基质。我们已经开发了舌头驱动系统(TDS)，可以通过固定在舌头上的钛磁体(Ti-Mag)实现舌头运动的实时无阻碍平移，用于计算机接口。尽管我们进行了技术创新，但由于缺乏关于钛镁种植体生物相容性和安全性的信息，TDS在人体上的应用仍被排除在外。在具体目标1中，我们测试了种植体设计(大小、形状、表面处理)和位置对种植体迁移和组织反应的影响，在兔模型中进行了缩放种植体，以更接近地反映种植体/舌部的比例。在特定目标2中，使用特定目标1中定义的最佳参数，我们定量评估了Ti-MAg植入和外植术后的解剖和分子反应。此外，我们还通过定量评估舔舌性能的变化来测试种植和植入术可能导致的舌功能缺陷。在具体目标3中，我们使用专为人类设计的装置在小型猪身上测试了钛-MAG植入和移植后的解剖、分子和生理反应。我们假设，在优化参数下的植入和外植只会产生轻微的局部组织反应(例如，装置封装)，不会损害可测量的舌功能。要在四肢瘫痪患者身上进行直接测试，必须证明设备的生物兼容性和安全性。

DESCRIPTION (provided by applicant): Individuals with high level spinal cord injury (SCI) have limited options for assistive control of their environments due in part to limited signal diversity for computer interface of patients' volitional motor systems. The tongue, a motor system capable of executing diverse movements under voluntary control, is spared in patients with high SCI and is thus a natural substrate for computer interfacing in quadriplegics. We have developed the tongue drive system (TDS) to allow unencumbered translation of tongue movements in real time for computer interfacing via a titanium-encased magnet (Ti-Mag) affixed to the tongue. Despite our technological innovation, TDS application in humans is precluded by a lack of information on Ti-Mag implant bio-compatibility and safety. In Specific Aim 1, we test the effect of implant design (size, shape, surfacing) and location on implant migration and tissue reaction in a rabbit model with a scaled implant to more closely reflect implant/tongue ratio in humans. In Specific Aim 2, using optimal parameters defined in Specific Aim 1, we quantitatively assess the anatomical and molecular responses to Ti-Mag implantation and explantation. We additionally test for possible deficit of tongue function due to implantation and explantation by quantitatively assessing changes in tongue lick performance. In Specific Aim 3 we test anatomical, molecular and physiological responses to Ti-Mag implantation and explantation in the mini-pig using a device designed for human application. We hypothesize that implantation and explantation under optimized parameters will produce only minor and local tissue reaction (e.g., device encapsulation) and will not impair measureable tongue function. Demonstration of device biocompatibility and safety is requisite to direct testing in humans with quadriplegia.