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（由申请人提供）：美国每年有 500 万新生儿，其中 50 万是早产儿。早产与大量的死亡率、发病率和不断上升的费用有关。早产并发症导致大量的呼吸系统、胃肠道、免疫和中枢神经系统发病率和显着的死亡率。特别是早产儿呼吸衰竭的有效治疗仍然是一个尚未解决的问题。已经制定了多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>34周2-3周的婴儿，需要全身肝素化并且不维持胎儿循环。为了规避其中许多挑战，开发通过脐带血管进入的泵驱动动静脉 AV-ECLS 回路形式的人工胎盘是一种有吸引力的替代方案。在过去的40年里，许多研究人员尝试制造人工胎盘，但由于技术有限，它从未超出概念阶段。我们的实验室开发了母胎羊模型，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开发该模型，为更长持续时间的实验做好准备。我们意识到这是一个长期项目，将对早产儿的护理产生重大影响。该提案的目标是开发一种早产羔羊动物模型，通过脐血管进行充分的体外气体交换，并维持血流动力学稳定性和正常的胎儿循环。该提案的具体目标是 1) 开发原型动静脉 ECLS 人工胎盘，包括脐血管通路和提供胎儿支持所需的技术； 2）在AV-ECLS期间维持24小时稳定的胎儿循环，特别注意识别那些会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主要健康问题。我们建议开发一种机械人工胎盘，使早产儿能够成长和茁壮成长，同时避免使用常规治疗带来的许多并发症。人工胎盘的开发将彻底改变早产儿的护理。