Artificial Placenta Device

描述(申请人提供)：美国每年有500万新生儿，其中50万是早产儿。早产与相当大的死亡率、发病率和不断攀升的成本有关。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。这些并发症中的许多都是直接或间接地由我们试图给未成熟的肺通风和逆转胎儿循环而引起的。虽然这些婴儿中有许多是通过常规治疗恢复的，但极低胎龄儿(Elgans)的死亡率和发病率非常高，极低胎龄儿的定义是比预期出生日期早3个月以上。目前的正压气体通气法存在机械损伤和肺部氧气中毒的高风险。早产儿产后治疗的一个主要模式转变将是避免正压通气的并发症，并使用人工胎盘(AP)重建胎儿环境，人工胎盘由四个独特功能组成：1)维持胎儿循环和环境；2)无机械通气；3)模拟胎儿呼吸，肺部充满液体；4)泵驱动的静脉-静脉体外生命支持(VV-ECLS)回路，经脐静脉流入，经右颈内静脉流出。我们在密歇根大学体外生命支持实验室(ECLS Lab)的合作伙伴已经证明了使用医疗组件进行完全体外支持的可行性和重复性，以模拟人造胎盘长达7天，具有血流动力学稳定、良好的气体交换、稳定的脑血流灌注和维持胎儿循环而不需要机械通气。这一研究项目的目标是设计和生产一种综合系统，它将作为人工胎盘发挥作用，用于极早产儿(胎龄28周)的产后治疗。我们的系统将支持埃尔根处于最自然的状态(即胎儿循环)，与目前的机械通气临床实践相比，我们的系统具有真正的创新性，并提供了许多治疗机会。L阶段的目标包括将MC3生物肺和MPump设备与盒式加热模块和自动扫气控制器集成在一起。该系统将被我们独特的无血栓形成的NO分泌聚合物覆盖，以减少或消除全身抗凝的需要。原型系统将在体外制造和测试，以证明安全性、有效性和耐用性。将进行一项体内试点研究，以证明胎儿有效的循环。第二阶段将包括对AP的安全性和有效性进行扩展的体内测试，以及开发一种临床就绪设备。密歇根大学体外生命支持实验室和MC3是这一领域的领先者，可以在四年内将这项技术变为现实。该项目具有很高的翻译潜力，并将影响 主要依靠对高危早产儿的护理。这项研究的成功完成将导致对垂死的早产儿进行临床试验。

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.