Regenerative Peripheral Nerve Interface for Restoring Individual Finger Movement in People with Upper Limb Amputations

用于恢复上肢截肢患者个体手指运动的再生周围神经接口

• 批准号: 10451527
• 负责人: Cynthia Anne Chestek
• 金额: $ 37.61万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10451527
• 关键词: Acute; Address; Adverse event; Amputation; Amputees; Autologous; Biological; Biological Process; Chronic; Classification; Clinical Data; Clinical Trials; Clinical assessments; Consent; Controlled Environment; Data; Devices; Distal; Electrodes; Engineering; Fascicle; Fingers; Funding; Goals; Hand; Health; Human; Implant; Individual; Institutional Review Boards; Intramuscular; Intuition; Lead; Length; Limb Prosthesis; Longevity; Methods; Monitor; Movement; Muscle; Natural regeneration; Nerve; Nerve Transfer; Neuroma; Noise; Operative Surgical Procedures; Pain; Participant; Patients; Performance; Peripheral Nerves; Persons; Phantom Limb Pain; Physical Medicine; Physical Rehabilitation; Procedures; Process; Prosthesis; Public Health; Rattus; Residual state; Rodent; Running; Safety; Schedule; Science; Seeds; Sensory; Signal Transduction; Specificity; Surface; Surgeon; Surveys; System; Techniques; Testing; Thumb structure; Time; Upper Extremity; Utah; War; Work; Wrist; base; biomechanical test; experience; fictional works; finger movement; human data; instrument; limb amputation; meetings; muscle grafts; muscle reinnervation; nerve transection; neural patterning; neuroprosthesis; neurotransmission; novel; patient population; pre-clinical; prevent; prosthesis control; prosthesis wearer; prosthetic hand; regenerative; reinnervation; relating to nervous system; sensory feedback; signal processing; ultrasound; wireless

Project Summary/Abstract There are approximately 50,000 people in the US with complete amputation of the hand, and many more with debilitating partial hand amputations. Treatments have not changed substantially since the body powered hook was invented during the civil war. While electrical signals from residual muscle can provide some function, every amputee is missing muscles, and therefore missing a variety of important functions. Attempts to record these signals from the nerves have suffered from low amplitude, low longevity, or both. Recently our group has demonstrated a novel method for obtaining signals from independent nerve fascicles in rats and NHPs, which we call the Regenerative Peripheral Nerve Interface (RPNI). Multiple dissected residual nerve branches are each placed in a 1x3 cm free muscle graft. The small muscle grafts degenerate, regenerate, revascularize, and reinnervate utilizing natural biologic processes. Upon completion of this regenerative process, the neurotized free muscle graft then amplifies a 5 μV cuff ENG into a >250 μV EMG signal. Most recently, we have replicated these results in 3 humans with upper limb amputation, routinely recording signals above 100 μV that correspond to individual finger movements. Our long-term goal is to provide intuitive high fidelity control of individual prosthetic fingers and enable naturalistic sensory feedback. The objective of the present application, which represents our proposed next step, is a pilot clinical trial of safety and bidirectional prosthetic control efficacy using the RPNI in 6 subjects. Our team includes the original developers of the RPNI concept, Drs. Cederna and Kung, who have since placed human RPNI implants in 65 patients for the control of neuroma pain. The team also includes two engineers, Drs. Chestek and Gillespie with complementary expertise in neural signal processing and prosthetic control. Dr. Chestek also has extensive experience in neuroprosthetic human clinical trials. Three specific aims have been constructed to address independent aspects of safety and efficacy of RPNis in humans during a 5 year study. In Aim 1, 6 participants will be implanted with multiple grafts on each severed nerve, following by indwelling EMG electrodes in a later procedure. Multiple validated instruments will be used to monitor pain and other potential adverse events during this process. In Aim 2, we will evaluate the amplitude, specificity, and longevity of the result neural signals for up to 12 months. In Aim 3, we will quantitatively determine whether enhanced finger control ultimately enables higher performance on tasks of daily living and embodiment with the prosthetic limb. The results of these aims will provide critical safety and efficacy data, and strongly motivate a larger, perhaps pivotal clinical trial across multiple years, using a wireless implantable neural recording device for EMG.

项目总结/摘要 在美国大约有5万人完全截肢，还有更多的人 使人虚弱的部分手部截肢。自人体动力钩以来， 是在内战期间发明的虽然来自残余肌肉的电信号可以提供一些功能， 每一个截肢者都缺少肌肉，因此失去了各种重要的功能。试图记录 这些来自神经的信号具有低振幅、低寿命或两者兼有的缺点。最近，我们的团队 证明了一种从大鼠和NHP的独立神经束获得信号的新方法， 我们称之为再生外周神经接口（RPNI）。多个解剖的残余神经分支 每个放置在1 × 3cm的游离肌肉移植物中。小肌肉移植物退化，再生，血管再生， 利用自然的生物过程进行再神经化。在完成这个再生过程后，神经化的 游离肌肉移植物然后将5 μ V袖带ENG放大成> 250 μ V EMG信号。最近，我们复制了 这些结果导致3名上肢截肢的人，常规记录高于100 μ V的信号， 对应于单个手指的运动。我们的长期目标是提供直观的高保真控制， 单独的假肢手指，并实现自然的感觉反馈。本申请的目的， 这代表了我们提出的下一步，是一个安全和双向假体的试点临床试验， 在6名受试者中使用RPNI的控制功效。我们的团队包括RPNI的原始开发人员 Cederna和Kung博士已经在65名患者中植入了人体RPNI植入物，以控制 神经瘤疼痛。该团队还包括两位工程师，Chestek博士和吉莱斯皮博士， 神经信号处理和假肢控制方面的专业知识。Chestek博士还拥有丰富的经验， 神经假体人体临床试验三个具体目标已经建立，以解决独立的 在一项为期5年的研究中，RPNis在人体中的安全性和有效性方面。在目标1中，将有6名参与者 在每个切断的神经上植入多个移植物，随后在随后的 procedure.将使用多种经确认的仪器监测疼痛和其他潜在不良事件 在这个过程中。在目标2中，我们将评估结果神经元的振幅、特异性和寿命。 信号长达12个月。在目标3中，我们将定量地确定增强手指控制是否 最终能够在日常生活任务上实现更高的性能，并与假肢一起实施。的 这些目标的结果将提供关键的安全性和有效性数据，并强烈激励一个更大的，也许 多年来的关键临床试验，使用无线植入式神经记录设备进行EMG。

项目成果

Restoration of Proprioceptive and Cutaneous Sensation Using Regenerative Peripheral Nerve Interfaces in Humans with Upper Limb Amputations.

• DOI: 10.1097/prs.0000000000009153
• 发表时间: 2022-06-01
• 期刊: Plastic and reconstructive surgery
• 影响因子: 3.6

A regenerative peripheral nerve interface allows real-time control of an artificial hand in upper limb amputees.

• DOI: 10.1126/scitranslmed.aay2857
• 发表时间: 2020-03-04
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Vu PP;Vaskov AK;Irwin ZT;Henning PT;Lueders DR;Laidlaw AT;Davis AJ;Nu CS;Gates DH;Gillespie RB;Kemp SWP;Kung TA;Chestek CA;Cederna PS
• 通讯作者: Cederna PS

The future of upper extremity rehabilitation robotics: research and practice.

• DOI: 10.1002/mus.26860
• 发表时间: 2020-06
• 期刊: Muscle & nerve
• 影响因子: 3.4
• 作者: Vu PP;Chestek CA;Nason SR;Kung TA;Kemp SWP;Cederna PS
• 通讯作者: Cederna PS

Artificial referred sensation in upper and lower limb prosthesis users: a systematic review.

• DOI: 10.1088/1741-2552/ac8c38
• 发表时间: 2022-09-08
• 期刊: JOURNAL OF NEURAL ENGINEERING
• 影响因子: 4
• 作者: Gonzalez, Michael;Bismuth, Alex;Lee, Christina;Chestek, Cynthia A.;Gates, Deanna H.
• 通讯作者: Gates, Deanna H.

Electrical Stimulation of Regenerative Peripheral Nerve Interfaces (RPNIs) Induces Referred Sensations in People With Upper Limb Loss.

再生周围神经接口 (RPNI) 的电刺激可引起上肢丧失患者的牵涉感觉。

• DOI: 10.1109/tnsre.2023.3345164
• 发表时间: 2024
• 期刊: IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society
• 作者: Gonzalez,MichaelA;Nwokeabia,Chinwendu;Vaskov,AlexK;Vu,PhilipP;Lu,CharlesW;Patil,ParagG;Cederna,PaulS;Chestek,CynthiaA;Gates,DeannaH
• 通讯作者: Gates,DeannaH