A Hydrogel Ionic Circuit-Based Electrical Stimulation System for Restoration of Denervated Muscles After Peripheral Nerve Injuries

基于水凝胶离子电路的电刺激系统，用于周围神经损伤后失神经肌肉的恢复

• 批准号: 10445353
• 负责人: Bin Duan
• 金额: $ 19.98万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-06 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445353
• 关键词: Action Potentials; Adverse effects; Animals; Chemical-Induced Change; Clinic; Clinical Trials; Coupled; Development; Device Designs; Devices; Electric Stimulation; Electrodes; Electrons; Exercise; Exploratory/Developmental Grant for Diagnostic Cancer Imaging; Generations; Goals; Human; Hydrogels; In Vitro; Ions; Lead; Mission; Modality; Modeling; Motor; Motor Neurons; Muscle; Muscle function; Muscle rehabilitation; Muscular Atrophy; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Nerve; Outcome; Patients; Peripheral nerve injury; Protocols documentation; Public Health; Quality of life; Rattus; Reaction; Recovery; Rehabilitation Outcome; Rehabilitation therapy; Research; Safety; Sensory; Signal Transduction; System; Technology; Temperature; Testing; Therapeutic; Tissues; Treatment Efficacy; base; effective therapy; efficacy evaluation; improved; in vivo; motor recovery; muscular structure; muscular system; novel; pre-clinical; preservation; prevent; restoration; therapy outcome; tool; wireless

Project Summary: Muscle electrical stimulation (EStim) is a promising rehabilitation modality for denervated muscles after peripheral nerve injuries. Current muscle EStim devices have limited therapeutic efficacy due to the low EStim intensity they apply. Applying high-intensity EStim to muscles presents a significant challenge. This is because all current devices conduct electron currents. Electrochemical reactions are required to convert the electron currents to the ion currents at the device-tissue interface. These reactions can induce chemical changes and temperature increase that can damage tissues when the EStim intensity is high. Thus, there is a critical need for a new generation of muscle stimulators that can safely apply high-intensity EStim for efficacious preservation of denervated human muscles. The long-term goal is to develop efficacious EStim-based therapy to preserve denervated human muscles after peripheral nerve injuries. The overall objectives of this proposal is to develop a novel EStim device that can safely apply high-intensity EStim to improve the preservation of denervated muscles. In Specific Aim 1, we will determine the optimal EStim device design for safe application of high-intensity EStim. Our working hypothesis is that a wirelessly coupled, ion current-conducting hydrogel ionic circuit (HIC) device does not induce any electrochemical reactions, so it can minimize adverse effects when applying high-intensity EStim. In Specific Aim 2, we will determine the efficacy of high-intensity EStim applied by our device for the preservation of denervated muscles using a pre-clinical rat peripheral nerve injury model. Our working hypothesis is that high- intensity EStim can improve muscle preservation compared to the low-intensity EStim typically used in current studies. The sensory recovery, motor recovery and muscle quality will be evaluated. The rationale for this project is that the development of a wirelessly coupled, completely ion current-based stimulator will significantly increase the EStim intensity that can be applied without causing tissue damage. This will lead to improved muscle rehabilitation outcomes following peripheral nerve injury that is not possible with current stimulators. Our outcome will establish an optimal device design to enable safe and efficient high- intensity EStim application. We will also demonstrate the in vivo efficacy of high-intensity EStim protocol for muscle preservation. Our high impact project will provide a strong justification for further development and testing of our device for treating denervated human muscles following peripheral nerve injuries. This will ultimately lead to better rehabilitation outcomes and improved quality of life for patients suffering from peripheral nerve injury.

项目摘要：肌肉电刺激 (EStim) 是一种很有前途的失神经康复方式 周围神经损伤后的肌肉。目前的肌肉 EStim 装置的治疗效果有限，因为 他们应用的低 EStim 强度。对肌肉应用高强度 EStim 是一项重大挑战。 这是因为所有当前的设备都会传导电子电流。需要电化学反应才能转化 设备-组织界面处的电子电流到离子电流。这些反应可以引发化学反应 当 EStim 强度较高时，变化和温度升高可能会损害组织。因此，有一个 迫切需要新一代肌肉刺激器，能够安全地应用高强度 EStim 以实现有效的治疗 保存去神经支配的人体肌肉。 长期目标是开发有效的基于 EStim 的疗法，以在术后保留去神经支配的人类肌肉 周围神经损伤。该提案的总体目标是开发一种新颖的 EStim 设备，该设备可以 安全地应用高强度 EStim 来改善去神经肌肉的保存。在具体目标 1 中，我们将 确定安全应用高强度 EStim 的最佳 EStim 设备设计。我们的工作假设 无线耦合的离子电流传导水凝胶离子电路 (HIC) 装置不会感应任何 电化学反应，因此可以最大限度地减少应用高强度 EStim 时的不利影响。具体来说 目标 2，我们将确定我们的设备应用的高强度 EStim 对保存 使用临床前大鼠周围神经损伤模型去神经化肌肉。我们的工作假设是高 与当前通常使用的低强度 EStim 相比，强度 EStim 可以改善肌肉保存 研究。将评估感觉恢复、运动恢复和肌肉质量。 该项目的基本原理是开发一种无线耦合、完全基于离子流的 刺激器将显着增加可应用的 EStim 强度，而不会造成组织损伤。这 将改善周围神经损伤后的肌肉康复结果，这是不可能的 电流刺激器。我们的成果将建立一个最佳的设备设计，以实现安全、高效的高 强度 EStim 应用。我们还将展示高强度 EStim 方案的体内功效 肌肉保存。我们的高影响力项目将为进一步开发和测试提供强有力的理由 我们的设备用于治疗周围神经损伤后失去神经的人类肌肉。这最终将导致 为周围神经损伤患者提供更好的康复效果并提高生活质量。

项目成果

Exosomes derived from differentiated human ADMSC with the Schwann cell phenotype modulate peripheral nerve-related cellular functions.

源自分化的具有施万细胞表型的人 ADMSC 的外泌体可调节周围神经相关的细胞功能。

• 发表时间: 2022-08
• 影响因子: 18.9
• 作者: Liu, Bo;Kong, Yunfan;Shi, Wen;Kuss, Mitchell;Liao, Ke;Hu, Guoku;Xiao, Peng;Sankarasubramanian, Jagadesan;Guda, Chittibabu;Wang, Xinglong;Lei, Yuguo;Duan, Bin
• 通讯作者: Duan, Bin

A Dual-network Nerve Adhesive with Enhanced Adhesion Strength Promotes Transected Peripheral Nerve Repair.

具有增强粘合强度的双网络神经粘合剂可促进切断的周围神经修复。

• 发表时间: 2023-01-10
• 影响因子: 19
• 作者: Xue, Wen;Shi, Wen;Kuss, Mitchell;Kong, Yunfan;Alimi, Olawale A;Wang, Hanjun;DiMaio, Dominick J;Yu, Cunjiang;Duan, Bin
• 通讯作者: Duan, Bin