Optimization, Biocompatibility and Safety Assessment of Tongue Implants

描述（由申请人提供）：高水平脊髓损伤（SCI）患者在辅助控制环境方面的选择有限，部分原因是患者意志运动系统的计算机接口信号多样性有限。舌头是一种能够在自主控制下进行多种运动的运动系统，在重度脊髓损伤患者中得以保留，因此是四肢瘫痪患者计算机接口的天然基础。我们已经开发了舌头驱动系统（TDS），通过贴在舌头上的钛包裹磁铁（Ti-Mag），可以不受阻碍地实时翻译舌头的运动，用于计算机接口。尽管我们在技术上有所创新，但由于缺乏关于钛镁植入物生物相容性和安全性的信息，TDS在人类中的应用受到了阻碍。在具体目标1中，我们测试了种植体设计（大小、形状、表面）和位置对种植体迁移和组织反应的影响，并在一个兔子模型中使用了缩放的种植体，以更接近地反映人类种植体/舌的比例。在特异性靶靶2中，使用特异性靶靶1中定义的最佳参数，我们定量评估了对Ti-Mag植入和外植的解剖和分子反应。我们还通过定量评估舌舔性能的变化来测试由于植入和外植体可能导致的舌功能缺陷。在Specific Aim 3中，我们使用一种为人类设计的装置，测试了迷你猪对钛镁植入和外植的解剖、分子和生理反应。我们假设在优化参数下植入和外植体只会产生轻微的局部组织反应（如器械封装），不会损害可测量的舌头功能。器械的生物相容性和安全性证明是在四肢瘫痪患者中进行直接试验所必需的。

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.