Artificial Placenta Device

人工胎盘装置

• 批准号: 8787193
• 负责人: George Boris Mychaliska
• 金额: $ 63.68万
• 依托单位: MC3, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-13 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8787193
• 关键词: Accounting; Animal Model; Anticoagulation; Birth; Blood; Blood Circulation; Blood flow; Blood gas; Breathing; Cannulas; Caring; Cerebrum; Characteristics; Clinical; Clinical Trials; Date of birth; Development; Devices; Drainage procedure; Engineering; Environment; Environmental air flow; Exposure to; Failure; Force of Gravity; Future; Gases; Gestational Age; Goals; Health; Heating; Hemolysis; Hour; In Vitro; Infant; Internal jugular vein structure; Lead; Life; Liquid substance; Lung; Maintenance; Measures; Mechanical ventilation; Mechanics; Medical; Michigan; Modeling; Morbidity - disease rate; Neuraxis; Newborn Infant; Nitric Oxide; Organ; Oxygenators; Performance; Perfusion; Phase; Placenta; Polymers; Pregnancy; Premature Birth; Premature Infant; Pump; Reproducibility; Research; Research Project Grants; Resuscitation; Running; Safety; Surface; System; Technology; Temperature; Testing; Therapeutic; Trauma; Umbilical vein; United States; Universities; Venous; clinical practice; cost; design; exhaust; extreme prematurity; fetal; gastrointestinal; hemodynamics; high risk; in vitro testing; in vivo; indexing; infant death; innovation; meetings; miniaturize; mortality; novel; oxygen toxicity; premature; pressure; prototype; respiratory; success; surfactant; treatment strategy

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.

美国每年有500万新生儿，其中50万是早产儿。早产与大量死亡率、发病率和不断上升的成本相关。早产的并发症包括呼吸道、胃肠道和中枢神经系统的发病率，以及显著的死亡率。这些并发症中有许多是直接或间接地由我们试图使未成熟的肺复苏和逆转胎儿循环引起的。虽然这些婴儿中有许多通过常规管理恢复，但极低胎龄新生儿（ELGAN）的死亡率和发病率非常高，ELGAN定义为在预产期前3个月出生。目前的正压气体通气方法具有机械创伤和肺氧中毒的高风险。早产儿出生后治疗的主要模式转变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（AP）包括四个独特的特征：1）维持胎儿循环和环境; 2）无机械通气; 3）用充满液体的肺模拟胎儿呼吸;以及4）一种新颖形式的泵驱动的静脉-静脉体外生命支持（VV-ECLS）回路，其具有经由脐静脉的流入和经由右颈内静脉的流出。 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使用医疗组件的完整体外支持的可行性和可重复性，以模拟长达7天的人工胎盘，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。该研究项目的目标是设计和生产一个集成系统，该系统将作为人工胎盘用于极早产儿（胎龄<28周）的产后治疗。我们的系统将在最自然的状态下支持ELGAN（即，胎儿循环），并且与当前的机械通气临床实践相比，是真正创新的，并提供了许多治疗机会。 阶段1的目标包括MC 3 BioLung和MPump设备与盒加热模块和自动吹扫气体控制器的集成。该系统将涂有我们独特的非血栓形成NO分泌聚合物，以减少或消除对全身抗凝的需要。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。将进行初步体内研究，以证明有效的胎儿循环。第二阶段将包括AP的安全性和有效性的扩展体内测试，以及临床就绪设备的开发。密歇根大学的Extracellular Life Support Lab和MC 3是该领域的领导者，可以在四年内将这项技术变为现实。该项目具有很高的翻译潜力， 这主要取决于高风险早产儿的护理。这项研究的成功完成将导致濒死早产儿的临床试验。