An Anticoagulation-Free Artificial Placenta Device

项目总结/摘要 极早产儿（EPT）的死亡率和发病率很高，主要是由于 肺部发育不全。在妊娠23周之前出生的婴儿通常被认为是非妊娠的。 可行的，并没有选择让他们活着。在23-27周之间，这些婴儿仍有较高的发病率 和死亡率，无重大并发症的出院存活率从27周时的43%到23周时的2%不等 周人工胎盘是体外膜肺氧合（ECMO）的一种适应， 早产儿并进行体外气体交换。人工胎盘模拟子宫内 生理学上，并可能使子宫外的持续正常发展。目前，人工 开发中的胎盘氧合器使用中空纤维膜（HFM）技术，该技术受到高 剂量抗凝要求和大预充体积。抗凝在EPT中尤其危险 婴儿由于大脑发育不全， 脉管系统 SiMOx-AP是一种新型微流控人工胎盘氧合器，设计用于在不抗凝的情况下运行， 从而克服了人工胎盘装置临床转化的关键障碍。它是基于突破 半导体硅基半渗透膜使用微加工技术制成。刚性 硅膜的平板性质克服了HFM和柔性微流体充氧器的局限性。 在本R21中，我们将研究临床规模的无抗凝SiMOx-AP器械的可行性， 计算、实验室和临床前体内研究的组合。

Project Summary/Abstract Extremely preterm (EPT) infants have a high rate of mortality and morbidity, primarily due to the underdevelopment of the lungs. When born before 23 weeks of gestation, infants are generally considered non- viable, and have no options to keep them alive. Between 23-27 weeks, these infants still have high morbidity and mortality, with survival to discharge without major morbidity varying between 43% at 27 weeks to 2% at 23 weeks. An artificial placenta is an adaptation of extracorporeal membrane oxygenation (ECMO) designed for a premature infant and performs extracorporeal gas exchange. An artificial placenta simulates intrauterine physiology and may enable continued normal development outside of the uterus. However, current artificial placenta oxygenators in development use hollow-fiber membrane (HFM) technology, which is limited by high- dose anticoagulation requirements and large priming volumes. Anticoagulation is especially dangerous in EPT infants, who already have high rates of intracranial hemorrhage due to their underdeveloped cerebral vasculature. The SiMOx-AP is a novel microfluidic artificial placenta oxygenator designed to operate without anticoagulation, thus overcoming a key barrier to clinical translation of an artificial placenta device. It is based on breakthrough semiconductor silicon-based semi-permeable membranes made using microfabrication techniques. The rigid and flat-plate nature of the silicon membranes overcome limitations of HFM and flexible microfluidic oxygenators. In this R21, we will investigate the feasibility of a clinical-scale and anticoagulation-free SiMOx-AP device using a combination of computational, benchtop, and preclinical in-vivo studies.