Development of the Osseointegrated Neural Interface for prosthetic control into a pre-clinical translational sheep model.

将用于假肢控制的骨整合神经接口开发成临床前转化绵羊模型。

• 批准号: 10494085
• 负责人: Samuel Poore
• 金额: --
• 依托单位: WM S. MIDDLETON MEMORIAL VETERANS HOSP
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10494085
• 关键词: Action Potentials; Address; Affect; Age; Age-Years; Aging; Amputation; Amputees; Anesthesia procedures; Animals; Biomechanics; Bone Density; Caring; Chronic; Communities; Conflict (Psychology); Data; Department of Defense; Development; Devices; Electrodes; Electronics; Electrophysiology (science); Etiology; Evaluation; Family member; Feedback; Female; Foundations; Funding; Future; Goals; Grant; Human; Implant; Individual; Injury; Joints; Knee; Life; Limb Prosthesis; Limb structure; Locomotion; Lower Extremity; Mechanics; Medical; Methods; Middle East; Modeling; Modernization; Motor; Nerve; Neurophysiology - biologic function; Operative Surgical Procedures; Oryctolagus cuniculus; Osseointegration; Outcome; Output; Pain management; Pathway interactions; Pattern; Peripheral Nerves; Peripheral arterial disease; Physical activity; Population; Pre-Clinical Model; Prosthesis; Quality of life; Recovery; Rehabilitation therapy; Research; Research Project Grants; Robotics; Route; Secondary to; Sensory; Sheep; Signal Transduction; Societies; Technology; Testing; Time; Touch sensation; Translating; Traumatic Amputation; Traumatic injury; United States Department of Veterans Affairs; Upper Extremity; Ursidae Family; Veterans; Women' s Role; Work; X-Ray Computed Tomography; active duty; awake; behavior test; clinical application; clinical translation; clinically significant; combat; design; disability; experience; improved; limb amputation; limb loss; male; military veteran; neural prosthesis; neurotransmission; novel; osseointegrated implant; peroneal nerve; pre-clinical; premature; pressure; prevent; programs; prosthesis control; prosthetic foot; relating to nervous system; response; sensory feedback; sensory input; sensory prosthesis; sheep model; skeletal; social determinants; subcutaneous; sural; tibia; usability; voltage; wireless; wound; wounded soldier

Clinical significance: Major amputation of a limb has a significant impact on an individual's quality of life, as well as directly affecting family members and the greater community. Veterans represent a unique population that are more greatly affected by amputation than the civilian population. The etiology of amputation in veterans is twofold. At one end of the spectrum there are the inevitable traumatic injuries of modern combat, particularly blast wounds from improvised explosives. These injuries predominantly affect young warriors, both male and female, under 30 years of age, who are increasingly experiencing major traumatic amputations of more than one limb at a time. At the other end of the spectrum, the aging veteran population is increasingly undergoing lower limb amputation secondary to peripheral arterial disease. Regardless of cause, most veterans live for many years after amputation, and bear the significant disabilities associated with losing one or more limbs. As such, there is an increasing demand for both the Department of Defense (DOD) and Department of Veterans Affairs (VA) to provide long-term financial and medical support to veteran amputees. Veteran and civilian amputees share the same physical and social determinants to quality of life, such as ability to participate in activity and pain management. The new age of robotic prostheses holds great promise for alleviating many if not all restrictions to physical activity and participation in greater society. However, the ability to seamlessly control a prosthesis as if the device were the original limb remains a futuristic goal. To specifically address the urgent need for better prosthesis control, we have devised the novel Osseointegrated Neural Interface (ONI) for prosthesis control on several fronts simultaneously. The ONI combines modern surgical procedures with state-of-the-art neural interfacing technology and osseointegration to form a single, compact unit, inside the medullary canal of the amputated limb. We have previously demonstrated in rabbits that an ONI is capable of bi-directional neural signaling, including motor signal output and sensory input that would serve for prosthesis control. Consequently, the objective of this grant is to translate our rabbit ONI model for prosthetic control into a preclinical large animal ovine (sheep) model, and implement a closed loop, osseointegrated, neural prosthetic with sensory feedback to be studied in a rehabilitation setting for future clinical translation. Our long-term goal is the clinical application of our novel ONI for prosthetic control to serve the veteran amputee community. Proposed Methods: A below knee amputation will be performed in a total of 10 skeletally mature sheep. An ONI will be created at the time of amputation by translocating the tibial, sural, and common peroneal nerves into the medullary canal of the amputated tibia via a corticotomy. The terminal ends of the nerves will be interfaced with cuff electrodes, connected to a wireless subcutaneous receiver/transmitter for chronic electrophysiology. The ONI will be completed by the integration of an osseointegrated abutment for prostheses attachment. After recovery, animals will be chronically evaluated for neural function via evoked action potentials through the ONI, bone density via computed tomography, and prostheses control via a battery of behavioral tests. Expected Outcomes: At the end of the funding period, we will understand in detail the requirements for creating a robust, chronic, osseointegrated neural interface for prosthetic control, including voltage limitations, action potential patterns, implant size limitations, and intramedullary capacity to house advanced electronics in combination with osseointegration. This foundational work will provide a direct route to clinical translation as well as a greatly needed pre-clinical model in which to test advanced paradigms of neural interfacing with closed loop feedback in a rehabilitation setting.

临床意义：肢体大截肢对个体的生活质量有显著影响，因为 并直接影响家庭成员和更大的社区。退伍军人代表了一个独特的群体 比平民更容易受到截肢的影响。截肢的病因 退伍军人是双重的。一方面是现代战争中不可避免的创伤， 特别是简易爆炸物造成的爆炸伤这些伤病主要影响年轻战士， 30岁以下的男性和女性，他们越来越多地经历着严重的创伤性截肢， 一次不止一个肢体在另一端，老龄化的退伍军人人口越来越多， 下肢截肢继发于外周动脉疾病。不管是什么原因，大多数 退伍军人在截肢后还能活很多年，并承受着与失去一个或多个肢体有关的严重残疾。 更多肢体因此，对国防部（DOD）和 退伍军人事务部（VA）为退伍军人截肢者提供长期的财政和医疗支持。 退伍军人和平民截肢者共享相同的身体和社会决定因素，以生活质量，如能力 参与活动和疼痛管理。机器人假肢的新时代为 减轻了对身体活动和参与更大社会的许多（如果不是全部的话）限制。但 无缝控制假肢的能力，就好像该装置是原始肢体一样，仍然是未来的目标。到 特别是解决迫切需要更好的假体控制，我们设计了新的骨整合 神经接口（ONI）用于同时在多个方面进行假肢控制。ONI结合了现代 采用最先进的神经接口技术和骨整合的外科手术， 紧凑的单元，在截肢的髓管内。我们之前已经在兔子身上证明了 ONI能够进行双向神经信号传导，包括运动信号输出和感觉输入， 将用于假肢控制。因此，该赠款的目的是将我们的兔子ONI模型 用于临床前大型动物绵羊（绵羊）模型中的假体控制，并实现闭环， 骨整合，神经假肢与感觉反馈，以研究在康复设置为未来 临床翻译。我们的长期目标是将我们的新型ONI应用于假肢控制， 截肢老兵社区 拟定方法：将对总共10只成年绵羊进行膝下截肢。一个 在截肢时，通过移位胫骨、腓肠和腓总神经创建ONI 通过皮质切开术进入截肢胫骨的髓管神经的末端会 与袖带电极连接，连接到无线皮下接收器/发射器，用于慢性 电生理学ONI将通过整合用于修复的骨整合基台来完成 附件.恢复后，将通过诱发动作长期评价动物的神经功能 通过ONI的电位，通过计算机断层扫描的骨密度，以及通过电池的假体控制， 行为测试 预期成果：在资助期结束时，我们将详细了解 为假肢控制，包括电压限制， 动作电位模式、植入物尺寸限制和髓内容纳先进电子器件的能力， 结合骨整合。这项基础性工作将为临床翻译提供直接途径， 以及一个非常需要的临床前模型，在其中测试神经接口的先进范例， 闭环反馈在康复设置。