A wireless fully-passive miniaturized patient-tailored pacemaker

无线全无源微型患者定制起搏器

• 批准号: 10002217
• 负责人: Jennifer M Blain Christen
• 金额: $ 17.84万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002217
• 关键词: Acoustics; Address; Anisotropy; Architecture; Atrial Fibrillation; Biocompatible Materials; Biomimetics; Caliber; Cardiac; Cardiac Myocytes; Cardiomyopathies; Cardiovascular Physiology; Cessation of life; Coronary; Coronary sinus structure; Data; Detection; Development; Electric Conductivity; Electrical Engineering; Electrocardiogram; Electrodes; Electronics; Freedom; Functional disorder; Generations; Goals; Gold; Heart; Heart failure; Heterogeneity; Histology; Human; Hydrogels; Hypertrophy; Impairment; Implant; In Vitro; Infection; Lead; Left; Location; Lung; Measures; Mechanics; Metals; Modeling; Monitor; Morphology; Myocardial Infarction; Myocardium; Pacemakers; Patients; Perforation; Performance; Physiologic pulse; Physiological; Pump; Rattus; Right ventricular structure; Risk; Rodent; Rodent Model; Safety; Signal Transduction; Site; Sprague-Dawley Rats; System; Technology; Telemetry; Testing; Therapeutic; Thoracotomy; Thrombosis; Tissue Model; Tissues; Tricuspid valve structure; Ultrasonography; Ventricular; Ventricular Arrhythmia; Wireless Technology; Work; absorption; base; biomaterial compatibility; cardiac tissue engineering; density; design; efficacy testing; flexibility; heart function; hemodynamics; human stem cells; implantation; improved; in vivo; in vivo evaluation; induced pluripotent stem cell; innovation; microwave electromagnetic radiation; miniaturize; minimally invasive; multidisciplinary; nanorod; nanoscale; next generation; personalized approach; phantom model; prototype; radio frequency; release of sequestered calcium ion into cytoplasm; response; rib bone structure; safety testing; sensor; transmission process

Summary Despite major advances in pacemaker technologies during the past decade, current pacemaker systems still suffer from several critical limitations. Primarily, the need to implant pacemaker leads within cardiac chambers could lead to a host of complications such as infection, thrombosis, tricuspid valve and ventricular perforation, along with the complications associated with the extraction of the lead when required. Furthermore, with traditional pacemakers, the cardiac regions accessible to pacing are restricted to right ventricle (RV, typically at the apex) and occasionally, coronary sinus distribution in cases of biventricular pacing. RV pacing creates abnormal left ventricular (LV) contraction, reduced pump function, hypertrophy, ultrastructural abnormalities and increases risk of atrial fibrillation, ventricular arrhythmias and ultimately heart failure and death. Leadless pacemakers address the issue associated with intravascular leads, but they remain limited in pacing only the RV and require placement of a new pacemaker after battery depletion. The recently developed remote ultrasound- powered wireless LV pacing electrode in conjunction with traditional pacemaker for biventricular pacing is technically limited by need for an acoustic window free of rib cage and lung on the transmission path to the electrode and the high density ultrasound drains battery quickly. To overcome the limitations of currently available pacemakers, we propose to develop the next generation of pacemaker system composed of wireless, miniaturized, battery-free, radiofrequency (RF) microwave activated sensor/stimulator electrodes that could be implantable and controlled by a remote pulse generator. In Aim 1, we will pursue technical development of miniaturized wireless sensor/stimulator electrodes, operating as a stand-alone platform, and remote pulse generator controller to monitor simulated cardiac signals and provide pacing signals using Micro-Electro-Mechanical-Systems (MEMS) and RF technologies on an organic phantom model while testing safety by measuring heat generation and extraneous RF interference. In Aim 2, we will test the wireless pacemaker system in vitro by measuring signal detection, pacing stimulation and tissue safety on our validated biomimetic cardiac micro-tissue model, using human induced pluripotent stem cell derived CMs (hiPSCs-CMs), as well as in vivo using a rodent thoracotomy model. We envision that the proposed innovative wireless pacemaker system could usher a paradigm shift in pacemaker therapeutics through the ability to pace precise regions of the heart resulting in more physiologic pacing and optimization of cardiac performance. !

总结 尽管在过去十年中起搏器技术取得了重大进展，但目前的起搏器系统仍然存在缺陷。 受到几个关键的限制。首先，需要在心腔内植入起搏器电极导线 可能导致一系列并发症，如感染、血栓形成、三尖瓣和心室穿孔， 沿着与在需要时取出电极导线相关的并发症。再加上 在传统的起搏器中，起搏可到达的心脏区域限于右心室（RV，通常在 在双心室起搏的情况下，偶尔会出现冠状窦分布。右心室起搏 左心室（LV）收缩异常、泵功能降低、肥大、超微结构异常和 增加房颤、室性心律失常的风险，并最终导致心力衰竭和死亡。无引线 起搏器解决了与血管内电极导线相关的问题，但它们仅限于右心室起搏 并且在电池耗尽后需要放置新的起搏器。最近开发的远程超声波- 电动无线LV起搏电极与传统起搏器联合用于双心室起搏， 技术上受限于在到肺的传输路径上需要没有胸腔和肺的声窗， 电极和高密度超声波消耗电池迅速。为了克服目前的局限性， 现有的起搏器，我们建议开发下一代的起搏器系统组成， 无线、小型化、无电池、射频（RF）微波激活传感器/刺激器 可以植入并由远程脉冲发生器控制的电极。在目标1中，我们将追求 小型化无线传感器/刺激器电极的技术开发，作为独立的 平台和远程脉冲发生器控制器，用于监测模拟心脏信号并提供起搏信号 在有机体模模型上使用微机电系统（MEMS）和RF技术， 通过测量发热和外部射频干扰来测试安全性。在目标2中，我们将测试无线 通过测量信号检测、起搏刺激和组织安全性，对体外起搏器系统进行验证。 仿生心脏微组织模型，使用人诱导多能干细胞衍生的CM（hiPSCs-CM）， 以及使用啮齿动物胸廓切开术模型在体内进行。我们设想，拟议的创新无线 起搏器系统可以通过精确起搏的能力， 心脏区域，从而导致更多的生理起搏和心脏性能的优化。 !