Miniaturization of the Artificial Placenta for Clinical Application

人工胎盘的小型化临床应用

• 批准号: 10428747
• 负责人: George Boris Mychaliska
• 金额: $ 19.5万
• 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/10428747
• 关键词: Address; Air; Animal Model; Anticoagulation; Argatroban; Autopsy; Blood Circulation; Blood Vessels; Blood flow; Brain; Breathing; Cannulas; Cannulations; Chronic lung disease; 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; base; 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.

项目摘要/摘要 早产与高死亡率和长期发病率有关。超过10年（由 R01HD073475）我们开发了专门维护的体外气体交换系统 胎儿循环，允许生长和发育而无需空气呼吸，并模拟人造的胎儿生理 胎盘（AP）。这项研究已完成以下内容：1）广泛评估的气体交换， 长期AP实验中的血液动力学和胎儿循环； 2）表征肺损伤和发育 与胎龄相匹配的胎儿羔羊和机械通风（MV）过早地递送的羔羊相比 控制并确定了最佳的气道维护策略； 3）评估脑充氧和灌注 在AP支持期间，并将AP大脑与使用后MRI的器官对照进行了比较，以评估出血， 白质伤害和发展； 4）完善一氧化氮（NO） / argatroban / no扫流策略 消除全身抗凝； 5）在过渡到空气之前证明肺发育和循环 呼吸和恢复； 6）对大脑，肺，心脏，脾脏，肾脏进行功能和组织学研究 和AP支持期间的肠。基于所有这些工作，我们现在有一个可重复的模型来优化 设备设计，解决人造胎盘的长期影响，并将AP微型化以进行临床 应用。基于这项工作，我们有一个可重现的模型来优化设备设计，并扩展 插管和设备达到了极端早产婴儿的大小。这项研究的目的是 将插管和电路微型化，并在小型动物模型中评估该系统的大小 极早的人类。 因此，该提案的具体目的是： 特定目的1：为临床应用做准备，通过小型化插管和电路并发展 AP系统的伺服调节。 特定目标2：评估过早的Minisheep中足够的支持和多机构结构和功能 模型。