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人设计的。 传统的植入式起搏器在解剖学上不适合新生儿和儿科患者， 导致治疗限制和一些短期和/或长期的不便。例如电流 临床体外临时起搏器与经皮起搏导线为早产儿患者（< 2kg）的使用天数非常有限，这是由于电极穿透 皮肤此外，这些经皮引线的移位与许多进一步的损伤相关。 并发症1，2.当需要永久性起搏器时，该器械的尺寸与新生儿不兼容。 和儿科患者，儿童身体的快速生长对设备产生压力， 导致组织电极接合处的导线断裂3。因此，年轻患者必须接受更多的 比成人更频繁的干预，以使他们的起搏器适应他们不断变化的解剖结构4，5。然而，在这方面， 起搏器部件的取出和更换是一种复杂的外科手术， 风险，包括撕裂周围的血管，刺穿心脏，血液凝块滞留在肺部， 最终失去血管通路4，6. 我们最近展示了一种完全可生物降解和生物相容的无线电刺激器 用于神经再生治疗7.我们成功的实验使我们假设， 电刺激将使一种新的可生物降解的新生儿心脏起搏器的发展成为可能。 和儿科患者。所提出的小型化装置（< 10 x 10 mm 2，< 100 mg）不仅将提供 在心外膜起搏的无线、无电池方式，以及通过再吸收的个性化器械寿命 在规定的时间间隔（6天~ 1+年）后，从而能够进行无感染的治疗性治疗， 减少移位的风险。此外，我们还将开发一种无线皮肤接口控制器， 实时心电监护、起搏器供电和蓝牙通信功能。把皮肤配对- 与生物可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活动。 具有闭环系统的可生物降解心脏起搏器的开发将创造一个 临床用生物可降解电子产品新方向的途径，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手术。这个专家团队将帮助我发展我的全面 潜力和启动我的职业生涯作为一个独立的，临床启发，生物医学工程研究员， 致力于改善患者的治疗效果。

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.