An Anticoagulation-Free Artificial Placenta Device

项目摘要/摘要 极早产儿的死亡率和发病率很高，主要原因是 肺部发育不全。当婴儿在怀孕23周之前出生时，通常被认为是非 是可行的，也没有办法让他们活下去。在23-27周之间，这些婴儿的发病率仍然很高。 死亡率，存活到出院而没有大的发病率从27周的43%到23周的2%不等 几周。人工胎盘是体外膜氧合(ECMO)的改编，专为 早产儿并进行体外气体交换。人造胎盘模拟宫内 并可能使子宫外的正常发育得以持续。然而，目前的人工 开发中的胎盘氧合器采用中空纤维膜(HFM)技术，但存在高效率的限制。 剂量抗凝要求和较大的预充量。抗凝在EPT中尤其危险 由于大脑发育不全，已经有很高的颅内出血率的婴儿 脉管系统。 SIMOX-AP是一种新型微流控人工胎盘氧合器，设计用于在没有抗凝的情况下操作， 从而克服了人工胎盘装置临床翻译的关键障碍。它建立在突破的基础上 采用微加工技术制备的半导体硅基半透膜。僵硬的 硅膜的平板性克服了HFM和柔性微流控氧合器的局限性。 在R21中，我们将研究临床规模和无抗凝血的SIMOX-AP设备的可行性，使用 计算型、台式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.