Opioid-Sparing Non-Surgical, Bioresorbable Nerve Stimulator for Pain Relief

项目摘要 缺乏有效的疼痛治疗促进了阿片类药物在美国的流行，估计造成了93,000人 2020年死亡人数增加，呼吁进行更有效和非阿片类药物的管理。一种替代的疼痛治疗方法是 通过神经刺激器，这是放置在周围神经或脊髓上的设备，使用电 调节痛觉的信号。大多数神经刺激器都是通过手术植入并由 永久性金属线。脉搏发生器和电池组也被外科手术植入皮肤下。这些 设备可以为患者提供有效的止痛，但并发症发生率过高，达30%至40%， 由于导线移动、断裂、不工作，或植入式电池组或永久性导线引起 新的痛点。这些并发症需要再做一次手术来纠正问题，从而增加了 病人和医疗保健系统。临时神经刺激器可以减轻一些并发症， 但这些都是永久性材料，必须在60天后拆除，而拆除会导致10- 15%的铅断裂，使铅永久留在体内。消失治疗公司提出了一种可生物吸收的、非 外科外周神经刺激器治疗慢性疼痛。一旦插入，该装置将提供电力 刺激长达60天，之后将通过施加阳极电刺激来安全地降解 导致身体吸收，消除了任何翻修手术的需要。这个第一阶段的项目将 确定第二阶段应用的可行性并产生安全性/有效性数据。为了实现这个目标，我们将 1)研制完全由生物可吸收成分组成的微创刺激引线。这个 电化学性质和降解曲线将被表征和优化，以满足应用 需要。刺激将在生理盐水溶液中进行测试，电极必须能够传递 至少550,000,000个刺激脉冲，相当于60天的全职临床刺激。生物多样性的退化 然后，该设备将通过阳极电刺激进行加速。材料/装置的毒性和 降解产品将按照ISO标准进行评估。 2)设计了具有可编程刺激电流波形和有源电源的可穿戴式外脉冲发生器 阻抗测量电路。该设备将提供缓解疼痛的电刺激，并驱动 刺激结束后钢丝的降解。 3)验证集成刺激器对大鼠神经病理性疼痛的刺激效果和降解安全性。 模特。使用之前开发的脉冲发生器和可注射电极，动物将被刺激 60天，每周进行一次电化学和电生理测量，监测电极功能。 在刺激后，电极会受到电力驱动的降解，导致快速的生物吸收 该设备的。植入后180天将进行组织学检查，以评估长期安全性和 退化特征。

Project Summary The lack of effective pain treatments has catalyzed the opioid epidemic in America, causing an estimated 93,000 deaths in 2020, calling for more effective and non-opioid based management. One alternative pain treatment is via nerve stimulators, which are devices placed near a peripheral nerve or on the spinal cord and use electrical signals to modulate the perception of pain. Most nerve stimulators are surgically implanted and made of permanent metal wires. A pulse generator and battery pack are also surgically implanted under the skin. These devices can provide effective pain relief to patients, but have excessively high complication rates of 30-40%, resulting from the wire moving, breaking, not working, or the implantable battery pack or permanent wire causing new sites of pain. These complications require yet another surgery to correct the problem, increasing costs for the patient and the healthcare system. Temporary nerve stimulators can mitigate some of the complications, but these are made of permanent materials and must be removed after 60 days, while the removal causes 10- 15% lead fracture leaving the lead permanently in the body. Vanish Therapeutics proposes a bioresorbable, non- surgical peripheral nerve stimulator to treat chronic pain. Once inserted, the device will provide electrical stimulation for up to 60 days, after which it will be safely degraded by applying an anodic electrical stimulus resulting in resorption by the body, eliminating the need for any revision surgeries. This Phase I project will establish feasibility and produce safety/efficacy data for a Phase II application. Towards this goal, we will 1) Develop the minimally invasive stimulation lead composed of entirely bioresorbable components. The electrochemical properties and degradation profile will be characterized and optimized to meet the application needs. Stimulation will be tested in physiological saline solution, and the electrode must be capable of delivering at least 550,000,000 stimulation pulses, equivalent to 60 days of full-time clinical stimulation. The degradation of the device will then be accelerated with an anodic electrical stimulus. The toxicity of the material/device and degradation products will be evaluated following ISO standards. 2) Design the wearable external pulse generator with programmable stimulation current profiles and an active impedance measurement circuit. The device will deliver the electrical stimulations for pain relief and drive the degradation of the wire after the end of stimulation. 3)Validate the stimulation efficacy and degradation safety of the integrated stimulator in a rat neuropathic pain model. Using the previously developed pulse generator and injectable electrode, animals will be stimulated for 60 days, with weekly electrochemical and electrophysiological measurements to monitor the electrode function. After stimulation, the electrode will be subjected to electrically driven degradation, resulting in rapid bioresorption of the device. Histology up to 180 days post-implant will be performed to evaluate the long term safety and degradation profile.