Development and Pre-Clinical Trial Qualification of a Pediatric Pump-Lung System for Children

项目摘要 需要可靠和有效的心肺支持设备的幼儿肺或心脏 失败是公认的。对于那些对常规治疗难治的儿科患者， 通过体外膜氧合（ECMO）进行积极的机械循环干预，或 心室辅助装置（VAD）可以提高生存的可能性。ECMO系统具有吸引力，因为 它们接近模拟生理气体交换和循环支持;但在实践中，这些系统 受限于其操作复杂性、机械故障、回路中的凝块和出血并发症。系统 在过去的十年里，儿科ECMO的应用并没有发生实质性的变化。改进成果，支持 患有心脏或肺衰竭的儿童主要是由于更好的选择和管理， 患者需要新设计的ECMO系统来持续降低发病率和死亡率。 我们提出了基于先进生物工程原理的新一代ECMO系统 专注于优化的血流路径和儿科ICU增强的患者移动性， 减少血小板粘附的涂层。 我们与行业合作伙伴合作开发了一系列微型，集成泵氧合器 对儿童和成人都是如此。这些装置联合收割机将独特构造的中空纤维膜与 新型血泵技术，使系统超紧凑，预充量低， 生物相容性儿科模型称为Pedi Pump-Lung（PediPL），专门设计用于 对于体重5-25 kg的患者，1）不足以稳定到脱离心肺功能的患者， 手术后旁路; 2）患有严重的原发性呼吸衰竭或与心脏相关的继发性衰竭 疾病;和3）经历严重的心源性休克，需要紧急支持。 该项目的目标是完善和完成PediPL和相关的开发 将附件连接到ECMO支持系统中，以提供动态呼吸和心肺支持， 对临床级PediPL的生产准备情况进行临床前评价， 按照良好生产规范（GMP）和良好实验室规范（GLP）进行检测， 预期510 K许可和试验用器械豁免（IDE）批准， FDA.

Project Summary The need for reliable and effective cardiopulmonary support devices for young children with lung or heart failure is well established. For those pediatric patients who become refractory to conventional therapies, aggressive mechanical circulatory intervention through extracorporeal membrane oxygenation (ECMO) or ventricular assist devices (VADs), may improve the likelihood of survival. ECMO systems are attractive since they closely simulate physiological gas exchange and circulatory support; but in practice, these systems are limited by their operational complexity, mechanical failure, clots in circuit, and bleeding complications. Systems for pediatric ECMO have not changed substantially in the last decade. Improved outcomes in support of children with either heart or lung failure have been principally due to better selection and management of the patients. A newly designed ECMO system is required for continued reduction in the morbidity and mortality. We propose to contribute a new generation ECMO system based on advanced bioengineering principles focused on an optimized blood flow path and pediatric ICU-enhanced patient mobility with biochemical coatings to reduce platelet adherence. We in partnership with industry partners have developed a series of miniature, integrated pump-oxygenators for both young children and adults. These devices combine uniquely configured hollow fiber membranes with novel blood pump technology, resulting in ultra-compact systems with a low priming volume and improved biocompatibility. The pediatric model, called Pedi Pump-Lung (PediPL), is specifically designed for use for up to 30 days in patients weighing 5-25 kg who 1) are not sufficiently stable to be weaned from cardiopulmonary bypass after surgery; 2) have severe primary respiratory failure or secondary failure associated with cardiac disease; and 3) experience profound cardiogenic shock and require urgent support. The objectives of this project are to refine and complete development of the PediPL and associated accessories into an ECMO support system permitting ambulatory respiratory and cardiopulmonary support and to conduct pre-clinical evaluation of readiness for manufacturing of the clinical grade PediPL and pre-clinical testing in compliance with Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP) in anticipation of anticipation of 510 K clearance and an Investigational Device Exemption (IDE) approval from FDA.