Multimodal wireless electrical stimulation for tissue regeneration

用于组织再生的多模式无线电刺激

• 批准号: 10615764
• 负责人: Song Li
• 金额: $ 47.23万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615764
• 关键词: Acceleration; Address; American; Atrophic; Autologous; Axon; Clinical; Development; Devices; Distal; Drug Delivery Systems; Electric Stimulation; Electrodes; Goals; Growth; Healthcare; Implant; Injury; Medical; Muscle; Muscular Atrophy; Nanotechnology; Natural regeneration; Nerve; Neuromuscular Junction; Neurons; Operative Surgical Procedures; Outcome; Patients; Peripheral; Peripheral Nerves; Peripheral nerve injury; Physical therapy; Physicians; Pilot Projects; Prevention; Protocols documentation; Recovery of Function; Regenerative Medicine; Regenerative capacity; Regenerative engineering; Research Personnel; Stem cell transplant; System; Technology; Testing; Therapeutic; Time; United States; Work; axon growth; axon regeneration; axonal sprouting; bioelectronics; improved; injured; innovation; miniaturize; minimally invasive; multidisciplinary; multimodality; muscle degeneration; nerve injury; neuromuscular; neuromuscular rehabilitation; novel; novel strategies; point of care; programs; regenerative therapy; reinnervation; repaired; sciatic nerve; synergism; therapy outcome; tissue regeneration; wireless; wireless electronic

Project Summary Twenty million Americans suffer from peripheral nerve injury, which results in approximately $150 billion health-care expenses annually in the United States. Approximately half of patients treated with nerve grafts have an inadequate level of function. Twenty million Americans suffer from peripheral nerve injury, which results in approximately $150 billion health-care expenses annually in the United States. Among various factors, axon growth rate and the lack of reinnervation and neuromuscular regeneration are two major road barriers. In many cases, during peripheral regeneration, the muscle undergoes atrophy and becomes un-receptive to reinnervation, and even the sprouting axons that regenerate across the gap cannot form functional neuromuscular junctions (NMJs). While most of the previous studies focus on accelerating peripheral nerve growth, novel approaches to maintain the neuromuscular receptivity and delay the degeneration of muscle need to be developed and integrated. Therefore, an integrative approach that combines the acceleration of axon growth and the prevention of muscle degeneration is required to address this unmet medical need, and we propose to use multimodal electrical stimulation (ES) to achieve this goal. Our recent studies have shown that repetitive ES either at the proximal or distal stumps of transected nerve can be more effective than one-time ES to further improve the therapeutic outcome, but their relative contributions to and their combined effects on axon growth, the slow-down of muscle atrophy and reinnervation remain to be investigated. Therefore, to investigate the potential synergistic effects of proximal and distal ES, we hypothesize that programmable ES at the proximal and distal stumps of sciatic nerve following a transection injury can promote axon growth and maintain muscle receptivity respectively and synergize neuromuscular regeneration. We will test this hypothesis by developing a wireless, stretchable, bioresorbable and miniaturized system that allows repetitive ES with versatile protocols. To address the aforementioned challenges and test our hypothesis, we have assembled a multidisciplinary team, and performed pilot studies to demonstrate the feasibility. We propose three Specific Aims: (1) To develop and characterize a bioresorbable, stretchable and wireless bioelectronic device for repetitive electrical stimulation. (2) To determine how the time periods of repetitive proximal and distal ES regulate muscle functional recovery. (3) To investigate the combined effects of proximal and distal ES on neuromuscular regeneration. This proposed project is timely with the recent advancement in regenerative engineering, micro/nanotechnologies, miniaturized wireless point-of-care devices, and bioresorbable and stretchable electrodes. This innovative bioelectronic device provides a novel and minimally invasive approach for neuromuscular regeneration, and will have wide applications in regenerative medicine and therapy.

项目概要 两千万美国人遭受周围神经损伤，导致大约 美国每年的医疗保健费用为 1500 亿美元。大约一半的患者接受治疗 神经移植物的功能水平不足。两千万美国人患有外围疾病 神经损伤，在美国每年造成约 1500 亿美元的医疗费用 国家。在各种因素中，轴突生长速度以及缺乏神经支配和神经肌肉 再生是两个主要的障碍。在许多情况下，在外周再生过程中，肌肉 经历萎缩并且变得不接受神经支配，甚至发芽的轴突 跨越间隙的再生不能形成功能性神经肌肉接头（NMJ）。虽然大多数 先前的研究重点是加速周围神经生长，维持神经生长的新方法 神经肌肉的感受能力和延缓肌肉的退化需要得到发展和整合。 因此，结合加速轴突生长和预防的综合方法 需要肌肉退化来解决这一未满足的医疗需求，我们建议使用 多模式电刺激（ES）来实现这一目标。我们最近的研究表明，重复 在横断神经的近端或远端残端进行 ES 比一次性 ES 更有效 进一步改善治疗结果，但它们的相对贡献及其综合效果 关于轴突生长、肌肉萎缩的减缓和神经支配的恢复仍有待研究。 因此，为了研究近端和远端 ES 的潜在协同效应，我们假设 横断损伤后坐骨神经近端和远端残端的可编程 ES 分别可以促进轴突生长和维持肌肉接受性并协同神经肌肉 再生。我们将通过开发一种无线、可拉伸、可生物吸收和 小型化系统，允许使用通用协议进行重复 ES。为了解决上述问题 挑战并检验我们的假设，我们组建了一个多学科团队，并进行了试点 研究论证可行性。我们提出三个具体目标： (1) 发展和 表征用于重复电的生物可吸收、可拉伸和无线生物电子设备 刺激。 (2) 确定重复近端和远端ES的时间段如何调节肌肉 功能恢复。 (3) 探讨近端和远端ES对神经肌肉的联合作用 再生。这个拟议的项目与再生工程的最新进展是及时的， 微/纳米技术、微型无线护理点设备以及生物可吸收和可拉伸 电极。这种创新的生物电子设备提供了一种新颖的微创方法 神经肌肉再生，并将在再生医学和治疗中具有广泛的应用。