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.

项目摘要 饮食和体重控制神经调节的最新突破已经激发了人们对 发展新的抗肥胖策略。但是，实现有效，实时和维护 具有最小副作用的电子神经调节仍然是一个重大挑战。为了应对这一挑战，这个 项目建议开发无电池，柔性和可植入的压电纳米发机剂（NG） 在迷走神经上产生闭环，生物反馈电刺激（ES）以控制食物摄入 响应胃部运动。该项目建立在Wang（PI）和CAI（CO-I）的协作工作的基础上 可植入的迷走神经刺激（VNS）装置，可在大鼠中实现有效的饮食和体重控制。 电池和无电子VNS设备连接到胃表面并产生替代 仅当胃在食物摄入量上移动时，电流（AC）信号直到迷走神经。 我们的初步研究表明，使用VNS设备的正常成年大鼠体重增加38％ 与在100天测试期内对照相比植入。尽管这种功效价值超过了 同行报告，与通常使用的ES信号强度相比，ES信号强度比1-2个数量级。我们 假设将闭环ES信号调整为典型的神经调节水平可能会进一步增加 减肥功效的表现优于当前使用的非天然连续ES。检验这一假设和 最终将这项有趣的技术带到诊所，我们建议开发一种压电NG 可调节的ES脉冲信号可响应胃蠕动，最多10 V，并且在长期内保持安全和稳定 术语植入。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势。在特定的目标1中，我们将开发生物材料 - 基于柔性的压电NGS可以响应模拟的胃而产生可调的ES脉冲 动作。在特定的目标2中，我们将评估胃中NG外体和体内的生物相容性 大鼠的植入部位和体内输出与胃运动相关。在特定的目标3中 我们将量化和比较三个肥胖大鼠模型的饮食和体重控制性能 使用曲折NGS进行VNS的不同策略：（1）电池供电的开环VN； （2）支持NG的自我 动力闭环VN； （3）NG开关电池供电的闭环VNS。 该项目将提供一种新型的基于生物材料的VNS设备，该设备无电池和电子产品的重量 控制。该项目使用大鼠模型测试新的VNS设备，为设备优化提供快速反馈， 并量化与ES信号相关的治疗功效。与植入相关的技术问题将 也可以解决。我们将共同建立一个基本的生物学和工程基础，将允许 我们要快速进入大型动物模型中体内研究的下一步，最终导致人类试验。