Miniaturization of the Artificial Placenta for Clinical Application

人工胎盘的小型化临床应用

• 批准号: 10678887
• 负责人: George Boris Mychaliska
• 金额: $ 23.4万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-08 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10678887
• 关键词: Address; Air; Animal Model; Anticoagulation; Argatroban; Autopsy; Blood Vessels; Blood flow; Brain; Breathing; Cannulas; Cannulations; Chronic lung disease; Circulation; Clinical; Development; Device Designs; Devices; Extremely low gestational age newborn; Fetal Sheep; Gases; Gestational Age; Goals; Growth and Development function; Heart; Hemorrhage; Hour; Human; In Vitro; Infant; Intestines; Kidney; Long-Term Effects; Lung; Magnetic Resonance Imaging; Maintenance; Mechanical ventilation; Miniaturization; Modeling; Morbidity - disease rate; Nitric Oxide; Organ; Outcome; Perfusion; Physiology; Placenta; Premature Birth; Premature Infant; Recovery; Reproducibility; Research; Research Project Grants; Research Proposals; Respiratory Failure; Safety; Spleen; Structure; System; Testing; United States; Work; cerebral oxygenation; clinical application; clinical implementation; clinical translation; conventional therapy; design; disability; effective therapy; experimental study; extreme prematurity; fetal; hemodynamics; histological studies; lung development; lung injury; miniaturize; mortality; pilot trial; premature; public health priorities; sheep model; white matter injury

PROJECT SUMMARY/ABSTRACT Prematurity is associated with high mortality and long-term morbidity. Over 10 years (supported by R01HD073475) we have developed an extracorporeal gas exchange system designed specifically to maintain fetal circulation, allow growth and development without air breathing, and simulate fetal physiology in an Artificial Placenta (AP). This research has accomplished the following: 1) extensively evaluated gas exchange, hemodynamics, and fetal circulation in long-term AP experiments; 2) characterized lung injury and development compared to gestational age-matched fetal lambs and mechanically ventilated (MV) prematurely delivered lamb controls and identified the best airway maintenance strategy; 3) assessed cerebral oxygenation and perfusion during AP support and compared AP brains to organ controls using postmortem MRI to assess for hemorrhage, white matter injury, and development; 4) refined the nitric oxide (NO) / argatroban / NO sweep flow strategy to eliminate systemic anticoagulation; 5) demonstrated lung development and circulation before transitioning to air breathing and recovery; and 6) performed functional and histologic studies of brain, lung, heart, spleen, kidney, and intestine during AP support. Based on all of this work, we now have a reproducible model to optimize device design, address long-term effects of the artificial placenta, and miniaturize the AP for clinical application. Based on this work, we have a reproducible model to optimize device design, and scale the cannulation and device to the size of extreme premature human infants. The goal of this research is to miniaturize the cannulas and circuit, and evaluate that system in a small animal model which is the size of extremely premature humans. As such, the specific aims of this proposal are: Specific Aim 1: To prepare for clinical application by miniaturizing the cannulas and circuit and develop servoregulation of the AP system. Specific Aim 2: To evaluate adequate support and multiorgan structure and function in a premature minisheep model.

项目总结/摘要 早产与高死亡率和长期发病率有关。10年以上（由 R 01 HD 073475）我们开发了一种体外气体交换系统，专门用于维持 胎儿循环，允许生长和发育，而无需空气呼吸，并在人工环境中模拟胎儿生理学。 胎盘（AP）。本研究取得了以下成果：1）广泛评价了气体交换， 血流动力学和长期AP实验中的胎儿循环; 2）表征肺损伤和发育 与胎龄匹配的胎羊和机械通气（MV）早产羔羊相比， 对照组并确定最佳气道维持策略; 3）评估脑氧合和灌注 在AP支持期间，使用死后MRI将AP大脑与器官对照进行比较以评估出血， 白色物质损伤和发展; 4）改进一氧化氮（NO）/阿加曲班/ NO扫描流策略， 消除全身抗凝; 5）在过渡到空气之前显示肺发育和循环 呼吸和恢复;和6）进行脑、肺、心脏、脾、肾 在AP支持期间，基于所有这些工作，我们现在有一个可重复的模型来优化 器械设计，解决人工胎盘的长期影响，并将AP用于临床 应用程序.基于这项工作，我们有一个可重复的模型，以优化器件设计，并扩大 插管和装置的尺寸与极早产的人类婴儿相当。这项研究的目的是 将套管和回路固定，并在小动物模型中评估该系统，该模型的大小为 极度早熟的人类 因此，这项建议的具体目标是： 具体目标1：通过对套管和回路进行灭菌，为临床应用做好准备，并开发 AP系统的伺服调节。 具体目标2：评价早产小型羊的充分支持和多器官结构和功能 模型