A Fully Biodegradable, Implantable, Wireless, Battery-free, Miniaturized Cardiac Pacemaker with Closed-loop System for Neonatal and Pediatric Patients

项目摘要 尽管起搏器技术取得了进步，但大多数起搏系统都是为成年人设计的。 传统的植入式起搏器在解剖学上不适用于新生儿和儿童患者， 导致治疗限制和几个短期和/或长期的不便。例如，Current 临床使用经皮起搏电极的早产儿临时起搏器(&lt； 2公斤)由于电极穿透部位的感染风险，使用天数非常有限。 皮肤。此外，这些经皮导线的移位与许多进一步的 复杂性1、2.当需要永久起搏器时，该装置的大小与新生儿不兼容 和儿科病人，而儿童身体的快速增长对设备造成压力，可以 导致组织-电极连接处的导线断裂。因此，年轻患者必须接受更多 成年人比成年人更频繁地进行干预，使起搏设备适应他们不断变化的身体结构。 起搏器部件的取出和更换是一项复杂的外科手术，不可避免地 风险，包括撕裂周围血管，心脏穿孔，血凝块滞留在肺部，以及 最终失去血管通路4，6。 我们最近演示了一种完全可生物降解和生物兼容的无线电刺激器 用于神经再生治疗7。我们的成功实验导致了这样一种假设，即 电刺激将使新生儿用新型可生物降解心脏起搏器的开发成为可能 和儿科病人。拟议的小型化设备(&lt；10 x 10 mm2，&lt；100 mg)将不仅提供 无线、无电池的心外膜起搏方式，还可以通过重新连接来个性化设备寿命 在规定的时间间隔(6天~1年)后，从而实现治疗而不感染和 降低被驱逐的风险。此外，我们还将开发一款无线的皮肤接口控制器， 实时心电监护、起搏器供电、蓝牙通讯等功能。把皮肤搭配在一起- 与可生物降解起搏器接口的控制器将实现无线闭环系统 自主心脏电疗，并允许年轻患者在治疗期间自由移动。 具有闭环系统的可生物降解心脏起搏器的开发将创造一种 临床使用的生物可降解电子产品的新方向，包括治疗和诊断 植入物。我的导师和研究合作者都是生物医学设计和制造方面的专家 设备、心脏电生理学和心脏外科。这个专家团队将帮助我充分发挥我的 作为一名独立的、受临床启发的生物医学工程研究人员， 致力于改善患者的预后。

Project Summary Despite the advancements in pacemaker technology, most pacemaking systems are designed for adults. The conventional implantable pacemakers are anatomically incompatible for neonatal and pediatric patients, causing therapeutic limitations and several short-term and/or long-term inconveniences. For example, current clinical external temporary pacemakers with percutaneous pacing leads for premature neonatal patients (< 2kg) have very limited days of use due to the risk of infection at the site where the electrodes penetrate the skin. Moreover, the dislodgement of these percutaneous leads is associated with many further complications1,2. When a permanent pacemaker is required, the device is incompatible in size for neonatal and pediatric patients, and the rapid growth of the child’s body creates pressures on the device that can cause fracturing in the leads at the tissue-electrode junction3. As a result, young patients must undergo more frequent interventions than adults to adapt their pacemaking devices to their changing anatomy4,5. However, extraction and replacement of pacemaker components is a complex surgical procedure with unavoidable risks, including tearing the surrounding blood vessel, perforating the heart, blood clot lodging in the lung, and eventual loss of vascular access4,6. We recently demonstrated an entirely biodegradable and biocompatible wireless electrical stimulator for neuroregenerative therapy7. Our successful experiments have led to the hypothesis that this approach of electrical stimulation will enable the development of a novel biodegradable cardiac pacemaker for neonatal and pediatric patients. The proposed miniaturized device (< 10 x 10 mm2,< 100 mg) will provide not only a wireless, battery-free means of pacing at the epicardium but also personalized device lifetime by resorbing after a defined time interval (6 days ~ 1+ year), thereby enabling therapeutic treatment without infection and reducing the risk of dislodgement. Additionally, we will develop a wireless, skin-interfaced controller with functions of real-time ECG monitoring, pacemaker powering, and Bluetooth communication. Pairing the skin- interfaced controller with the biodegradable pacemaker will realize a wireless, closed-loop system for autonomous cardiac electrotherapy and allow young patients to move freely during treatment. The development of the biodegradable cardiac pacemaker with a closed-loop system will create a pathway for new directions in biodegradable electronics for clinical use, including therapeutic and diagnostic implants. My mentors and research collaborators are experts in the design and fabrication of biomedical devices, cardiac electrophysiology, and cardiac surgery. This team of experts will help me to develop my full potential and launch my career as an independent, clinically inspired, biomedical engineering researcher, working to improve patient outcomes.