Soft, conformal wireless optoelectronic systems for the long-term neuromodulation of bladder function

用于膀胱功能长期神经调节的柔软、共形无线光电系统

• 批准号: 9744141
• 负责人: Robert W Gereau
• 金额: $ 12.73万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-25 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9744141
• 关键词: Address; Anti-Inflammatory Agents; Anti-inflammatory; Bladder; Bladder Control; Bladder Diseases; Bladder Dysfunction; Blood flow; Chronic; Collaborations; Deterioration; Development; Devices; Disease; Electric Stimulation; Electrodes; Esthesia; Feedback; Gene Delivery; Goals; Health; Inflammation; Inflammation Mediators; Interstitial Cystitis; Light; Maintenance; Measurement; Measures; Mechanics; Mediator of activation protein; Microfluidics; Modality; Monitor; Nerve; Neurogenic Bladder; Neurons; Optics; Organ; Overactive Bladder; Pathology; Performance; Peripheral; Peripheral Nerves; Positioning Attribute; Pump; Regulation; Sensory; Source; System; Technology; Temperature; Therapeutic; Thinness; Time; Tissues; United States; Visceral; Wireless Technology; Work; base; bladder pain; design; flexibility; improved; insight; minimally invasive; neuroinflammation; neuronal circuitry; neuroregulation; new technology; novel; optogenetics; programs; relating to nervous system; remote control; sensor; success; tool

Abstract Bladder pain and dysfunction are sources of profound debilitation for millions of people in the United States with interstitial cystitis/bladder pain syndrome, overactive bladder, and neurogenic bladder. Current treatments for these disorders are ineffective and do not address the underlying pathology. A substantial barrier to the development of improved therapeutics is an insufficient understanding of mechanisms by which the bladder is controlled. Progress will depend critically on the development of new technologies in neural interfaces. In particular, a combination of optogenetic approaches along with new, wireless optoelectronic systems and electronic hardware for nerve recording and electrical stimulation will provide a unique set of tools for enhanced insights into peripheral organ control. Additionally, the ability to measure, in real-time, neural inflammation and to programmably deliver local anti-inflammatory agents at the neural interface will not only allow robust, high performance chronic integration, but also further the understanding of maintenance at nerve- device interfaces in other applications. In this proposal, we develop a suite of soft, fully-implantable microscale devices with advanced design features specifically configured to minimize and mitigate inflammation for essentially permanent integration with the targeted nerves. In Aim 1, we propose to integrate optogenetic technologies with fully-implantable wireless systems for inhibition of peripheral neurons innervating the bladder. In Aim 2, we propose to integrate ultra-thin, flexible electrode technology and novel neuroinflammatory monitors to the wireless control of bladder peripheral nerves. In Aim 3, we integrate a fully-implantable, wirelessly programmable microfluidic platform for closed-loop maintenance of the chronic nerve interface. Our collaborative team has extensive success merging technologies into unified multi-modal devices and subsequently applying them to the mechanistic study of neuronal subpopulations. The technology produced by these aims will be optimally positioned to study mechanisms of control of end-organ function, and to do so in a way that is minimally invasive.

摘要 膀胱疼痛和功能障碍是美国数百万人严重衰弱的原因 间质性膀胱炎/膀胱疼痛综合征、膀胱过度活动症和神经源性膀胱。当前治疗 对于这些疾病是无效的，并且不能解决潜在的病理学。一个实质性的障碍， 改进的治疗方法的发展是对膀胱炎的机制的理解不足， 控制。进展将主要取决于神经接口新技术的发展。在 特别是，光遗传学方法与新的无线光电系统的组合沿着， 用于神经记录和电刺激的电子硬件将提供一套独特的工具， 增强了对外周器官控制的了解。此外，能够实时测量神经 炎症并在神经界面可编程地递送局部抗炎剂不仅将 允许强大的，高性能的慢性整合，但也进一步了解维护神经， 其他应用中的设备接口。在这个提议中，我们开发了一套柔软的，完全可植入的微型 具有先进设计特征的器械，专门配置用于最大限度地减少和减轻炎症， 与目标神经基本上永久整合。在目标1中，我们建议整合光遗传学， 技术与完全植入式无线系统，用于抑制周围神经元支配 膀胱在目标2中，我们提出将超薄柔性电极技术和新型神经炎性 监测器到膀胱周围神经的无线控制。在目标3中，我们整合了一个完全可植入的， 无线可编程微流体平台，用于慢性神经界面的闭环维护。我们 协作团队在将技术融合到统一的多模式设备中方面取得了广泛的成功， 随后将其应用于神经元亚群的机制研究。所产生的技术 通过这些目标，将最佳地定位于研究终末器官功能的控制机制，并且这样做 以一种微创的方式。