Multimodal wireless electrical stimulation for tissue regeneration

项目摘要 2000万美国人患有外周神经损伤，这导致大约 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。2000万美国人患有边缘性 神经损伤，导致美国每年约1500亿美元的医疗保健费用 States.在各种因素中，轴突生长速度和缺乏神经再支配和神经肌肉 再生是两个主要的道路障碍。在许多情况下，在外周再生期间，肌肉 经历萎缩，变得不接受神经再生，甚至是发芽的轴突， 再生跨越差距不能形成功能性神经肌肉接头（NMJ）。虽然大多数 以前的研究集中在加速周围神经的生长，新的方法来维持周围神经的生长。 神经肌肉感受性和延缓肌肉退化需要发展和整合。 因此，结合轴突生长的加速和预防的综合方法， 肌肉退化是需要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， 在离断神经的近端或远端进行ES比一次性ES更有效 进一步改善治疗结果，但它们的相对贡献和它们的联合作用 在轴突生长方面，肌肉萎缩和神经再支配的减缓仍有待研究。 因此，为了研究近端和远端ES的潜在协同作用，我们假设 在坐骨神经横断损伤后的近端和远端残端的可编程ES 分别促进轴突生长和维持肌肉感受性， 再生我们将通过开发一种无线的、可拉伸的、生物可吸收的 小型化系统，允许重复ES与通用协议。解决上述 挑战和测试我们的假设，我们已经组建了一个多学科的团队，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 表征用于重复电气的生物可吸收、可伸展和无线生物电子设备 刺激. (2)确定重复近端和远端ES的时间周期如何调节肌肉 功能恢复(3)研究近端和远端ES对神经肌肉的联合作用， 再生这个拟议的项目是及时的，与最近的进步，在再生工程， 微/纳米技术，小型化的无线即时护理设备，以及生物可吸收和可拉伸的 个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。

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.