Implantable Self-Powered Biofeedback Vagus Nerve Stimulator for Weight Control

用于体重控制的植入式自供电生物反馈迷走神经刺激器

• 批准号: 10801765
• 负责人: Xudong Wang
• 金额: $ 43.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-25 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10801765
• 关键词: Address; Adult; Animal Model; Animals; Benchmarking; Biocompatible Materials; Biofeedback; Biological; Body Weight decreased; Charge; Clinic; Clinical; Development; Devices; Eating; Eating Behavior; Electric Stimulation; Electronics; Engineering; Evaluation; Extravasation; Feedback; Film; Foundations; Glycine; Human; Implant; In Vitro; Legal patent; Maintenance; Mechanics; Modeling; Motion; Movement; Obesity; Output; Performance; Peristalsis; Physiologic pulse; Physiology; Rattus; Reporting; Series; Signal Transduction; Site; Stomach; Structure; Surface; Techniques; Technology; Testing; Therapeutic Intervention; Time; Treatment Efficacy; Vagus nerve structure; Weight Gain; Weight maintenance regimen; Width; Work; adult obesity; bariatric surgery; biomaterial compatibility; comparison control; design; dietary control; flexibility; implantable device; implantation; in vivo; interest; mechanical properties; miniaturize; multidisciplinary; neuroregulation; novel; obesity treatment; operation; packaging material; peer; randomized trial; response; side effect; vagus nerve stimulation

Project Summary Recent breakthroughs in neuromodulation for diet and weight control have stimulated a growing interest in the development of new anti-obesity strategies. However, achieving effective, real-time, and maintenance-free electrical neuromodulation with minimal side effects remains a major challenge. To address this challenge, this project proposes to develop a battery-free, flexible, and implantable piezoelectric nanogenerator (NG) that produces closed-loop, biofeedback electrostimulation (ES) on the vagus nerves to control food intake in response to stomach motions. This project builds on the collaborative work by Wang (PI) and Cai (co-I) of an implantable vagus nerve stimulation (VNS) device, which achieved effective diet and weight control in rats. The battery- and electronics-free VNS device is attached to the stomach surface and generates alternative current (AC) ES signals to the vagus nerves only when the stomach moves upon food intake. Our preliminary study demonstrated 38% less weight gain on normal adult rats with the VNS device implantation as compared to controls over a 100-day testing period. Although this efficacy value surpassed most peer reports, the ES signal intensity was 1-2 orders of magnitude smaller compared to those typically used. We hypothesize that tuning the closed-loop ES signal to the typical level of neuromodulation may further increase weight loss efficacy outperforming the currently-used non-natural continuous ES. To test this hypothesis and eventually bring this intriguing technology to clinic, we propose to develop a piezoelectric NG that provides tunable ES pulse signals up to 10 V in response to stomach peristalsis, and remains safe and stable over long- term implantation. We will also optimize the implantation of the VNS device and validate the closed-loop VNS efficacy and advantages to using standard obese rat models. In Specific Aim 1, we will develop a biomaterial- based flexible piezoelectric NGs that can produce tunable ES pulses in response to simulated stomach movements. In Specific Aim 2, we will evaluate the biocompatibility of the NG ex vivo and in vivo on the stomach of rats, and examine implantation sites and in vivo outputs in correlation to stomach motions. In Specific Aim 3, we will quantify and compare the diet and weight control performances on two obese rat models among three different strategies of using on-stomach NGs for VNS: (1) battery-powered open-loop VNS; (2) NG-enabled self- powered closed-loop VNS; (3) NG-switched battery-powered closed-loop VNS. This project will deliver a novel biomaterial-based VNS device that is battery- and electronics-free for weight control. This project uses rat model to test the new VNS devices, providing rapid feedback for device optimization, and quantifying the therapeutic efficacy in correlation to ES signals. Implantation-related technical issues will also be addressed. Together, we will establish an essential biological and engineering foundation that will allow us to move rapidly to the next step of in vivo studies in large animal models, eventually leading to human trials.

项目概要 最近在饮食和体重控制的神经调节方面取得的突破激发了人们日益增长的兴趣 制定新的抗肥胖策略。然而，实现有效、实时、免维护 副作用最小的电神经调节仍然是一个重大挑战。为了应对这一挑战，本 项目建议开发一种无电池、灵活、可植入的压电纳米发电机（NG） 对迷走神经产生闭环生物反馈电刺激 (ES) 以控制食物摄入 响应胃部的运动。该项目建立在王（PI）和蔡（co-I）的合作基础上 植入式迷走神经刺激（VNS）装置，实现了大鼠的有效饮食和体重控制。 无需电池和电子设备的 VNS 设备附着在胃表面，并产生替代品 仅当胃因进食而移动时，当前 (AC) ES 才会向迷走神经发出信号。 我们的初步研究表明，使用 VNS 装置的正常成年大鼠的体重增加减少了 38% 在 100 天的测试期内与对照进行比较。虽然这个功效值超越了大多数 同行报告显示，ES 信号强度比通常使用的信号强度小 1-2 个数量级。我们 假设将闭环 ES 信号调整到神经调节的典型水平可能会进一步增加 减肥效果优于目前使用的非自然连续ES。为了检验这个假设并 最终将这项有趣的技术带入临床，我们建议开发一种压电NG，它可以提供 可调谐 ES 脉冲信号高达 10 V，以响应胃蠕动，并长期保持安全稳定 足月植入。我们还将优化 VNS 设备的植入并验证闭环 VNS 使用标准肥胖大鼠模型的功效和优点。在具体目标 1 中，我们将开发一种生物材料- 基于柔性压电 NG，可响应模拟胃产生可调谐 ES 脉冲 动作。在具体目标 2 中，我们将评估 NG 离体和体内在胃上的生物相容性 大鼠，并检查与胃运动相关的植入部位和体内输出。在具体目标 3 中， 我们将量化并比较三个肥胖大鼠模型中两个肥胖大鼠模型的饮食和体重控制表现 使用胃上NG进行VNS的不同策略：（1）电池供电的开环VNS； (2) NG启用自 动力闭环 VNS； (3) NG开关电池供电闭环VNS。 该项目将提供一种基于生物材料的新型 VNS 设备，该设备无需电池和电子设备，重量轻 控制。该项目使用大鼠模型来测试新的VNS设备，为设备优化提供快速反馈， 并量化与 ES 信号相关的治疗效果。与植入相关的技术问题将 也得到解决。我们将共同建立一个重要的生物和工程基础，使 我们将迅速进入大型动物模型体内研究的下一步，最终进行人体试验。