Artificial Placenta Device

描述（由申请人提供）：美国每年有500万新生儿，其中50万为早产儿。早产与大量的死亡率、发病率和不断上升的成本有关。早产的并发症包括呼吸系统、胃肠道和中枢神经系统的发病率，以及显著的死亡率。许多并发症都是由于我们试图给未成熟的肺部通气和逆转胎儿循环而直接或间接引起的。虽然这些婴儿中有许多通过常规治疗得以康复，但极低胎龄新生儿（ELGANs）的死亡率和发病率非常高，ELGANs定义为在预产期前3个月以上出生。目前的正压气体通气方法有很高的机械创伤和肺氧中毒风险。避免正压通气并发症，利用人工胎盘（AP）重建胎儿环境是早产儿产后治疗的一个主要模式转变，人工胎盘具有四个独特的特点：1)维持胎儿循环和环境；2)无机械通气；3)肺充液模拟胎儿呼吸；4)一种新型的泵驱动的静脉-静脉体外生命支持（VV-ECLS）回路，通过脐静脉流入，通过右颈内静脉流出。我们在密歇根大学体外生命支持实验室（ECLS实验室）的合作者已经证明了完全体外支持的可行性和可重复性，用医疗组件模拟人工胎盘长达7天，具有血流动力学稳定性，良好的气体交换，稳定的脑灌注，以及在没有机械通气的情况下维持胎儿循环。本研究项目的目标是设计和生产一个集成系统，作为人工胎盘，用于早产儿（小于28周胎龄）的产后治疗。我们的系统将支持elgan在最自然的状态下（即胎儿循环），与目前的机械通气临床实践相比，这是真正的创新，提供了许多治疗机会。第一阶段的目标是将MC3 BioLung和MPump设备与插装热模块和自动扫气控制器集成在一起。该系统将涂覆我们独特的非血栓性NO分泌聚合物，以减少或消除系统抗凝的需要。原型系统将在体外制造和测试，以证明安全性、有效性和耐久性。一项试点体内研究将进行，以证明有效的胎儿循环。ii期将包括扩大AP的安全性和有效性的体内测试，以及临床准备设备的开发。密歇根大学体外生命支持实验室和MC3是该领域的领导者，可以在四年内将这项技术变为现实。该项目具有很高的转化潜力和影响力

DESCRIPTION (provided by applicant): There are 5 million births in the United States each year of which 500,000 are premature. Prematurity is associated with substantial mortality, morbidity, and escalating cost. The complications of premature birth include respiratory, gastrointestinal, and central nervous system morbidity, and significant mortality. Many of these complications are caused, directly or indirectly, by our attempts to ventilate the immature lungs and reverse fetal circulation. Although many of these babies recover with conventional management, the mortality and morbidity of extremely low gestational age newborns (ELGANs) defined as born more than 3 months before the expected date of birth, is very high. The current approach of positive pressure gas ventilation carries high risks of mechanical trauma and oxygen toxicity to the lungs. A major paradigm shift in the post-natal treatment of prematurity would be to avoid the complications of positive pressure ventilation and recreate the fetal environment with an Artificial Placenta (AP) which consists of four unique features: 1) maintaining fetal circulation and environment; 2) no mechanical ventilation; 3) simulated fetal breathing with fluid filled lungs; and 4) a novel form of a pump-driven veno-venous extracorporeal life support (VV-ECLS) circuit with inflow via the umbilical vein and outflow via the right internal jugular vein. Our collaborators at the University of Michigan Extracorporeal Life Support Lab (ECLS Lab) have demonstrated feasibility and reproducibility of complete extracorporeal support with medical components to simulate an artificial placenta for up to 7 days with hemodynamic stability, excellent gas exchange, stable cerebral perfusion, and maintenance of fetal circulation without mechanical ventilation. The goal of this research project is to design and produce an integrated system that will function as an Artificial Placenta for the post-natal treatment of very premature infants (<28 weeks gestational age). Our system will support ELGANs in the most natural state (i.e., fetal circulation), and is truly innovative and offers many therapeutic opportunities when compared to current clinical practice with mechanical ventilation. Phase l aims include integration of the MC3 BioLung and MPump devices with cartridge heat modules and an automated sweep gas controller. The system will be coated with our unique nonthrombogenic NO secreting polymer to decrease or eliminate the need for systemic anticoagulation. The prototype system will be fabricated and tested in vitro to demonstrate safety, efficacy and durability. A pilot in vivo study will be conducted to demonstrate effective fetal circulation. Phase ll will include extended in vivo testing of AP for safety and efficacy, and the development of a clinical ready device. The University of Michigan Extracorporeal Life Support Lab and MC3 are the leaders in this field and can bring this technology to reality in four years. This project has high translational potential and would impact substantially upon the care of high risk premature newborns. Successful completion of this research will lead to a clinical trial in moribund premature infants.