Optimization, Biocompatibility and Safety Assessment of Tongue Implants

描述（由申请人提供）：由于患者意志运动系统的计算机接口的信号多样性有限，因此患有高水平脊髓损伤（SCI）的个体对其环境的辅助控制的选择有限。舌头是一个能够在自主控制下执行各种运动的运动系统，在高度SCI患者中是幸免的，因此是四肢瘫痪患者计算机接口的天然基质。我们已经开发了舌头驱动系统（TDS），以允许不受阻碍的翻译舌头运动在真实的时间的计算机接口通过钛包裹的磁铁（钛镁）贴在舌头上。尽管我们进行了技术创新，但由于缺乏有关Ti-Mag植入物生物相容性和安全性的信息，TDS在人类中的应用仍无法实现。在特定目标1中，我们在家兔模型中测试了植入物设计（尺寸、形状、表面）和位置对植入物移位和组织反应的影响，该模型使用缩放的植入物，以更接近地反映人类的植入物/舌比。在特定目标2中，使用特定目标1中定义的最佳参数，我们定量评估了对Ti-Mag植入和再结晶的解剖学和分子反应。此外，我们还通过定量评估舌舔性能的变化来测试由于植入和移行导致的舌功能的可能缺陷。在特定目标3中，我们使用专为人体应用设计的器械测试了小型猪对Ti-Mag植入和再植入的解剖学、分子和生理反应。我们假设在优化参数下的植入和再植入将仅产生轻微的局部组织反应（例如，器件封装）并且不会损害可测量的舌功能。必须证明器械的生物相容性和安全性，以指导在四肢瘫痪的人体中进行试验。

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.