Atraumatic Non-fibrotic Epicardial Pacing with E-Bioadhesive Devices

项目摘要 在美国，每年有近100万名患者接受心脏手术，围手术期心律失常 包括心动过缓和完全度心脏传导阻滞在内的异常是最常见和致命的 心脏手术的并发症。心外膜临时起搏电极的置入是治疗的标准 接受心脏手术以提供按需心脏起搏的患者。事实证明，这些线索是必要的 控制约15%的心脏手术后潜在危及生命的缓慢性心律失常 病人。目前的临时心外膜起搏电极有两大局限性：1)创伤性 植入和移除过程。在植入时，将导线形式的传统引线穿透到 要锚定的心外膜。这种方法使患者面临局部出血的风险，可能是心脏出血。 腔体穿孔和填塞。1-2周后，这些并发症的风险甚至更高 通过将起搏导线从心外膜中拔出来移除起搏导线。2)炎症诱导的捕获 阈值升高和早期器件故障。创伤和异物反应导致纤维性包膜 在铅-组织界面形成，这会导致捕获损失和早期器件故障。例如，60% 右房导联至术后第15天失效，左房导联失效达80%。 为了应对上述挑战，我们建议开发一种导电的 生物粘合(e-生物粘合)设备可提供：1)强大的无创集成和按需 以及2)在装置-组织界面处没有纤维包膜形成，因此提供 稳定有效的起搏能力，提高患者在整个住院过程中的安全性。初步 来自《自然》、《自然材料》、《自然生物医学工程》和《科学》的MPI联合出版物的数据 转化医学证实，我们的电子生物粘合剂可以形成即时、坚固和导电的 粘合到湿的动态器官，还提供按需拆卸。在这里，我们的目标是开展一系列 体外、体外、啮齿动物和猪的体内研究，以开发和系统地基准我们的电子生物粘附剂 直接与商业上使用的临时性心外膜导联进行比较。我们将彻底评估和 优化e-生物粘合剂的附着和分离机制、传感和起搏能力，以及 评估组织对电子生物粘合剂的反应。建议的电子生物黏附装置的设计应 允许轻松合并到现有的临床场景中进行临时心脏起搏，进一步加快了 这项技术的临床翻译。

Project Summary Almost a million patients undergo heart surgery annually in the US, and perioperative heart rhythm abnormalities including bradycardia and complete-degree heart block are one of the most common and fatal complications of cardiac surgery. Implantation of temporary epicardial pacing leads is the standard of care for patients undergoing cardiac surgery to provide on-demand pacing of the heart. Such leads prove necessary to control potentially life-threatening bradyarrhythmias in approximately 15% of all post-operative cardiac surgery patients. The current temporary epicardial pacing leads suffer from two major limitations: 1) Traumatic implantation and removal processes. At implantation, the conventional leads in form of wires are pierced into the epicardium to be anchored. This approach puts patients at risk of local hemorrhage, possibly cardiac chamber perforation, and tamponade. After 1-2 weeks, the risk of these complications is even higher following the removal of the pacing leads, by pulling them out of the epicardium. 2) Inflammation-induced capture threshold elevation and early device failure. Trauma and foreign body response cause fibrous capsule formation at the lead-tissue interface, which leads to loss of capture and early device failure. For instance, 60% of right and 80% of left atrial leads fail by the 15th postoperative day. To address the abovementioned challenges, we propose to develop an electrically conductive bioadhesive (e-bioadhesive) device that can offer: 1) robust atraumatic integration and on-demand atraumatic removal, and 2) no fibrous capsule formation at the device-tissue interface, therefore providing stable and effective pacing capability and improving patient safety throughout the hospitalization. Preliminary data from joint publications of the MPIs in Nature, Nature Materials, Nature Biomedical Engineering, and Science Translational Medicine validate that our e-bioadhesives can form instant, robust, and electrically conductive adhesion to wet dynamic organs and also offer on-demand detachment. Here we aim to conduct a series of in vitro, ex vivo, and rodent and porcine in vivo studies to develop and systematically benchmark our e-bioadhesive devices in direct comparison to commercially used temporary epicardial leads. We will thoroughly assess and optimize the e-bioadhesives’ attachment and detachment mechanisms, sensing and pacing capabilities, and evaluate the tissue response to the e-bioadhesive. The design of the proposed e-bioadhesive devices should allow for easy incorporation into existing clinical scenarios for temporary cardiac pacing, further accelerating the clinical translation of this technology.