Collaborative Research: A Hybrid Biological-Microelectronic Pacemaker

项目目标描述：该项目研究一种植入式混合生物-微电子起搏器，该起搏器结合了生物和电心脏起搏来治疗心律失常。摘要：虽然心律失常是对公众健康的严重威胁，每年折磨数百万美国人，但目前的治疗方法仍然不足或主要是姑息性的。心脏起搏的临床治疗完全依赖于传统的电子起搏器，它不能评估患者的完整生理状态或动态改变起搏。近年来，干细胞技术的进步为生物起搏打开了大门，通过植入工程起搏器组织来恢复心跳，但在实践中成功率较低。提出的混合生物-微电子起搏器系统结合了“生物”和“电子”起搏的优点，并解决了它们的局限性。首先，它解决了传统电子起搏器的局限性，采用工程心脏起搏器细胞作为“全谱”细胞传感器，可以产生自然的心脏起搏信号，并根据患者的实时生理状况（如神经递质释放、激素水平变化和心脏药物刺激）自主调节起搏速率。此外，所提出的混合起搏器将大大提高生物起搏器的成功率和寿命。活的起搏器细胞将被放置在一个生物兼容的包中，该包可以定位细胞，提高其生存能力，并允许在部署前对其进行表征。此外，超低功耗微电子将包括在内，以实现安全起搏和高强度心脏刺激的信号调理。拟议中的混合起搏器将产生广泛的社会影响。它可能会彻底改变心律失常相关疾病的治疗，大大提高临床成功率，每年使数百万美国人受益。此外，该系统可为心血管生理学和植入式装置的基础和临床研究提供新的科学探索工具。该项目还探索了许多科学界感兴趣的混合生物电子学研究前沿。这个项目提供了独特的跨学科教育机会。ppi将通过现有的GT和Emory项目招收少数族裔本科生。研究结果将被整合，例如，作为课堂演示，在生物电子学和生物工程课程在GT和埃默里大学。pi将特别强调为亚特兰大当地少数民族高中学生提供K-12教育。研究结果将在出版物、会议、网站和社交媒体上传播。技术摘要：本项目旨在研究一种新型的生物-微电子混合起搏器系统，该系统综合了生物起搏器和电子起搏器的优点，并探索其在心律失常治疗中的应用。所提出的混合起搏器包含一个超小型和超低功耗的可植入混合起搏器产生模块，与常规电子起搏器协同工作。混合起搏产生模块采用从头培养起搏细胞作为“生物起搏信号合成器”，产生自然起搏，实时响应患者生理状况和神经体液刺激。这些起搏器细胞被封装在CMOS集成电路（IC）芯片上，该芯片检测合成的起搏信号，进行信号调理，并通过体内传输将起搏信号发送给电子起搏器。研究活动包括(1)设计用于生物起搏器信号传感、调理和传输的超低功耗CMOS IC；(2)在CMOS上进行起搏器细胞的分化和培养；(3)利用水凝胶基质和3d打印技术设计生物兼容封装；(4)进行临床相关生物实验演示。本项目将探索并建立生物-微电子混合起搏器，作为治疗心律失常的突破性解决方案。这些研究活动和探索将最终为未来的混合生物电子系统铺平道路。

Title: Collaborative Research: A Hybrid Biological-Microelectronic PacemakerDescription of Project Goals: This project investigates an implantable hybrid biological-microelectronic pacemaker that combines biological and electrical cardiac pacing to treat cardiac arrhythmia.Abstract:Nontechnical Abstract:Although the cardiac arrhythmia is a serious threat to the public health and afflicts millions of Americans annually, current treatments remain either inadequate or largely palliative. Clinical therapies for cardiac pacing rely exclusively on conventional electronic-only pacemakers that cannot evaluate the patients' full physiology states or change the pacing dynamically. Recent stem-cell technology advance opens the door to biological pacing by engrafting engineered pacemaker tissues for heartbeat restoration, which however faces low success rate in practice.The proposed hybrid biological-microelectronic pacemaker system combines the advantages of the "biological" and "electrical" pacing and addresses their limitations. First, it solves the limitation of conventional electronic pacemakers by employing engineered cardiac pacemaker cells as "full-spectrum" cell-based sensors that can generate natural cardiac pacing signals and autonomously adjust the pacing rate in response to the patient's real-time physiology conditions, e.g., neurotransmitter release, hormone level shifts, and cardiac drug stimuli. Moreover, the proposed hybrid pacemaker will substantially improve the success rate and lifetime of the biological pacemakers. The living pacemaker cells will be hosted in a bio-compatible package that localizes the cells, enhances viability, and allows their characterizations before deployment. Furthermore, ultra-low-power microelectronics will be included to enable signal conditioning for safe pacing and high-intensity cardiac stimulation.The proposed hybrid pacemaker will lead to broad societal impacts. It will potentially revolutionize the treatment of arrhythmia-related diseases, substantially increase the clinical success rate, and benefit millions of Americans annually. Moreover, the proposed system can serve as a novel research tool for scientific exploration in fundamental and clinical research on cardiovascular physiology and implantable devices. This project also explores hybrid bioelectronics research frontiers, which are of interest to many scientific communities.This project offers unique interdisciplinary education opportunities. The PIs will recruit minority undergraduates through existing GT and Emory programs. The research results will be integrated, e.g., as classroom demos, in the bioelectronics and bioengineering courses at GT and Emory. The PIs will particularly emphasize K-12 education outreach for local minority high school students in Atlanta. The research results will be disseminated at publications, conferences, websites, and social media.Technical Abstract: The goal of this project is to investigate a novel hybrid biological-microelectronic pacemaker system that harnesses the advantages of both biological pacemaker and electronic pacemaker and explore its use in treating cardiac arrhythmia.The proposed hybrid pacemaker contains an ultra-miniaturized and ultra-low-power implantable hybrid pacing generation module co-operating with a regular electronic pacemaker. The hybrid pacing generation module employs de novo cultured pacemaker cells as a "biological pacing signal synthesizer" to generate natural pacing and respond to the real-time patient physiology conditions and neurohumoral stimuli. These pacemaker cells are encapsulated and hosted on a CMOS integrated circuit (IC) chip that detects the synthesized pacing signals, performs signal conditioning, and sends the pacing signals to the electronic pacemaker by intra-body transmission. The research activities include (1) designing the ultra-low-power CMOS IC for biological pacing signal sensing, conditioning, and transmission, (2) pacemaker cells differentiation and culture on CMOS, (3) designing bio-compatible packaging using hydrogel matrix and 3D-printing, and (4) demonstrations with clinically relevant biological experiments.This project will explore and establish hybrid biological-microelectronic pacemaker as a disruptive solution for treating cardiac arrhythmia. The research activities and explorations will eventually pave the way toward hybrid bioelectronics systems in the future.