Development of an Artificial Placenta

人工胎盘的开发

• 批准号: 7773104
• 负责人: George Boris Mychaliska
• 金额: $ 7.56万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7773104
• 关键词: Address; Animal Model; Animals; Attention; Birth; Blood Circulation; Blood Vessels; Caring; Data; Development; Environment; Gases; Goals; Health; Hour; Immune; Infant; Laboratories; Life; Maintenance; Mechanical ventilation; Mechanics; Modeling; Morbidity - disease rate; Neuraxis; Newborn Infant; Phase; Placenta; Pregnancy; Premature Birth; Premature Infant; Pump; Research; Research Personnel; Resources; Respiratory Failure; Sheep; Techniques; Technology; United States; Venous; conventional therapy; cost; effective therapy; experience; fetal; gastrointestinal; hemodynamics; mortality; novel; premature; prototype; public health relevance; research study; respiratory; treatment strategy

DESCRIPTION (provided by applicant): There are 5 million births in the United States each year of which 500,000 are premature. Premature delivery is associated with substantial mortality, morbidity and escalating cost. The complications of premature birth result in substantial respiratory, gastrointestinal, immune and central nervous system morbidity and significant mortality. In particular, effective treatment of respiratory failure in premature infants remains an unsolved problem. Several strategies have been developed to support these infants, including refinements in mechanical ventilation and the use of extracorporeal life support (ECLS) in severe respiratory failure. ECLS is limited to infants >34 weeks gestation for 2-3 weeks, requires systemic heparinization and does not maintain fetal circulation. To circumvent many of these challenges, the development of an artificial placenta in the form of a pump-driven arterio-venous AV-ECLS circuit with access via the umbilical vessels is an appealing alternative. For the last 40 years, many investigators have tried to make an artificial placenta but it has never gone beyond the concept phase because of limited technology. Our laboratory has developed a maternal-fetal sheep model with preliminary data demonstrating the feasibility to address this problem. We aim to further characterize and develop this model to prepare for longer duration experiments. We realize that this is a long term project which will impact substantially upon the care of premature newborns. The goal of this proposal is to develop an animal model in the preterm fetal lamb with full extracorporeal gas exchange via the umbilical vessels and maintenance of hemodynamic stability and normal fetal circulation. The specific aims of this proposal are 1) to develop a prototype arterio-venous ECLS artificial placenta including umbilical vessel access and the techniques necessary to provide fetal support; and 2) to maintain stable fetal circulation during AV- ECLS for 24 hours, with particular attention to identify those factors which will limit practical long-term application. PUBLIC HEALTH RELEVANCE: The complications associated with premature birth remain a major unsolved health problem. We propose development of a mechanical artificial placenta that would allow a premature infant to grow and thrive while avoiding the many complications using conventional treatment. Development of an artificial placenta would revolutionize the care of premature infants.

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。早产的并发症导致大量呼吸道、胃肠道、免疫和中枢神经系统的发病率和显著的死亡率。特别是，对早产儿呼吸衰竭的有效治疗仍然是一个尚未解决的问题。已经制定了几种策略来支持这些婴儿，包括改进机械通气和在严重呼吸衰竭时使用体外生命支持(ECLS)。ECLS仅限于妊娠2-3周的34周的婴儿，需要全身肝素化，不维持胎儿循环。为了绕过这些挑战，开发一种由泵驱动的动-静脉AV-ECLS回路形式的人造胎盘，并通过脐血管进入是一个有吸引力的替代方案。在过去的40年里，许多研究人员试图制造人造胎盘，但由于技术有限，它从未超越概念阶段。我们实验室已经建立了母羊-胎儿模型，初步数据证明了解决这一问题的可行性。我们的目标是进一步表征和发展这一模型，为更长时间的实验做准备。我们认识到，这是一个长期项目，将对早产儿的护理产生重大影响。该方案的目的是建立一种通过脐带血管进行充分的体外气体交换、维持血流动力学稳定和正常胎儿循环的早产儿羔羊动物模型。这项建议的具体目标是1)开发动静脉ECLS人工胎盘原型，包括脐带血管通路和提供胎儿支持所需的技术；2)在AV-ECLS期间保持24小时稳定的胎儿循环，特别注意识别那些限制实际长期应用的因素。 公共卫生相关性：与早产相关的并发症仍然是一个尚未解决的重大健康问题。我们建议开发一种机械人造胎盘，使早产儿能够成长和茁壮成长，同时避免使用传统治疗的许多并发症。人工胎盘的开发将彻底改变早产儿的护理。