An Anticoagulation-Free Artificial Placenta Device

一种免抗凝人工胎盘装置

• 批准号: 10741704
• 负责人: SHUVO ROY
• 金额: $ 46.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10741704
• 关键词: 3-Dimensional; Acute; Adult; Affect; Animals; Anticoagulation; Area; Bathing; Blood; Blood flow; Carbon Dioxide; Cell Membrane Permeability; Cerebrovascular system; Clinical; Coagulation Process; Computer-Aided Design; Dangerousness; Development; Device Designs; Devices; Diffusion; Dimensions; Dose; Drops; Engineering; Environment; Extracorporeal Membrane Oxygenation; Fiber; Future; Gases; Gestational Age; Goals; Hematocrit procedure; Hemoglobin; Hour; Human; In Vitro; Infant; Intracranial Hemorrhages; Liquid substance; Membrane; Microfabrication; Microfluidic Microchips; Microfluidics; Modeling; Morbidity - disease rate; Nature; Oxygen; Oxygenators; Patients; Permeability; Physiology; Placenta; Plasma; Platelet Count measurement; Pregnancy; Premature Infant; Semiconductors; Sheep; Silicon; Structure of umbilical artery; Surface; Techniques; Technology; Testing; Umbilical vein; United States; Uterus; clinical translation; design; exhaust; extreme prematurity; falls; flexibility; hemocompatibility; improved outcome; in vivo; lamb model; lung development; meetings; mortality; novel; nutrition; operation; pre-clinical; premature; pressure; scale up

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.

项目概要/摘要 极早产儿 (EPT) 的死亡率和发病率较高，主要是由于 肺部发育不全。妊娠 23 周之前出生的婴儿通常被认为是非妊娠期婴儿。 可行，并且没有选择让他们活下去。 23-27周期间，这些婴儿的发病率仍然很高 和死亡率，无重大发病情况的出院生存率从 27 周时的 43% 到 23 周时的 2% 不等 几周。人工胎盘是体外膜肺氧合 (ECMO) 的改良版，专为 早产儿并进行体外气体交换。人工胎盘模拟宫内 生理学，并可能使子宫外持续正常发育。然而，目前的人工 正在开发的胎盘充氧器使用中空纤维膜（HFM）技术，该技术受到高 剂量抗凝要求和大预充量。抗凝治疗在 EPT 中尤其危险 婴儿，由于大脑发育不全，颅内出血的发生率很高 脉管系统。 SiMOx-AP 是一种新型微流控人工胎盘充氧器，设计无需抗凝即可操作， 从而克服了人工胎盘装置临床转化的关键障碍。是基于突破 采用微加工技术制成的半导体硅基半透膜。僵化的 硅膜的平板特性克服了 HFM 和柔性微流体充氧器的局限性。 在此 R21 中，我们将研究临床规模且无需抗凝的 SiMOx-AP 设备的可行性，该设备使用 计算、台式和临床前体内研究的结合。