DEVELOP A HEMOCOMPATIBLE, EASY-TO-USE, COST-EFFECTIVE BLOOD PURIFIC

用于输血的红细胞(RBC)产品在储存过程中会经历代谢和物理变化，其特征是RBC“储存损伤”，可能导致血管外溶血和炎症、血管收缩，并可能在输血时损害氧合。针对这一缺陷，我们提出了合理的设计和开发HemoDefend，这是一种血液兼容、高度多孔的聚合物微珠，基于成熟的孔捕获和表面吸附技术平台，经过优化，可以从存储的红细胞中广泛去除污染物，如游离血红蛋白、钾、反应性抗体、生物活性脂类、炎性细胞因子、反应蛋白和微囊。这些血液相容的珠子将以两种配置进行评估：1)袋装珠子，和2)可对接的直插式过滤器。在第一种方法中，珠子将被直接放入血袋中，以在储存期间吸附血液污染物。在第二种方法中，珠子将被包含在放置在血袋和患者之间的一个小的直排式墨盒中。在确定最佳聚合物吸附剂后，我们将评估每种测试配置从pRBC单元中去除11种污染物和炎症介质的能力。考虑到与红细胞的广泛直接接触，我们将特别评估七个参数来评估候选微珠的血液相容性。我们还将使用图像捕获和差异细胞计数来评估HemoDefend治疗是否可以防止存储的红细胞发生一些有害的形态变化。其结果将是展示一种强大且易于使用的血液净化技术，以维护并潜在地改善储存血液的质量和安全。

Red blood cell (RBC) products for transfusion undergo metabolic and physical changes during storage characterized as RBC "storage lesions" that may result in extravascular hemolysis and inflammation, vasoconstriction, and potentially compromised oxygenation upon transfusion. To address this defect, we have proposed the rational design and development of HemoDefend, a hemocompatible, highly porous polymer bead optimized to broadly remove contaminants such as free hemoglobin, potassium, reactive antibodies, bioactive lipids, inflammatory cytokines, reactive proteins and microvesicles from stored pRBCs based on a proven pore capture and surface adsorption technology platform. These hemocompatible beads would be assessed in two configurations: 1) Beads-in-a-Bag, and 2) a dockable, in-line filter. In the first approach, the beads will be placed directly into the blood bag to adsorb blood contaminants during the storage period. In the second approach, the beads would be contained in a small in-line cartridge placed between the blood bag and the patient. After identifying optimal polymer sorbents, we will evaluate each test configuration for the ability to remove 11 contaminants and inflammatory mediators from pRBC units. Given the extended direct contact with erythrocytes, we will specifically evaluate seven parameters to assess hemocompatibility of the bead candidates. We will also evaluate whether HemoDefend treatment can prevent some of the deleterious morphological changes that occur to stored RBCs using image capture and differential cell counting. The outcome will be the demonstration of a powerful and easy-to-use blood purification technology to maintain and potentially improve the quality and safety of stored blood.