BIOENGINEERING DESIGN OF ARTIFICIAL BLOOD

人工血液的生物工程设计

• 批准号: 6390649
• 负责人: Marcos Intaglietta
• 金额: $ 96.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-05 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6390649
• 关键词: bioengineering /biomedical engineering; biomaterial development /preparation; biotechnology; blood /plasma substitute; hamsters; hemoglobin; laboratory mouse; laboratory rat; polyethylene glycols

DESCRIPTION: (verbatim) We plan to design, develop, and produce an economic oxygen carrying plasma expander based on modified molecular human hemoglobin engineered with properties that insure the maintenance of microvascular function, leading to improved survival and tissue oxygenation relative to blood, for treatment of trauma victims within 48 hours of injury. The program is vertically integrated, including production of purified hemoglobin from red blood cells by means of a modified, self contained plasma fractionation centrifuge ~at directly produces the necessary molecular modifications and a unit of artificial blood ready for use. This approach eliminates the need for fabrication of large, clean facilities and reduces cost. Furthermore it allows for production in remote areas. Our bioengineering design principle is that when a blood replacement fluid is introduced in the circulation it should cause the resulting blood viscosity to remain sufficiently elevated to insure the adequate generation of shear stress at the-blood/tissue interface, which we have demonstrated to be necessary to provide normal capillary blood flow the key -determinant of tissue survival. According to this principle even small amounts of cell-free hemoglobin (l-2 g/dl) are very effective in improving survival after hemorrhage. Due to this low-dose effect at least two units of product can be obtained from each unit of collected normal blood. The molecular modification to be pursued is surface modification with polyethylene glycol (PEG), and other modifications that will result in molecules with large radius. Different formulations of product are envisioned including a low volume concentrated solution that will restore blood volume by autotransfusion. The program encompasses all aspects of artificial blood production from obtaining the raw materials to the final commercial product and is aimed at; establishing a blood transfusion technology that delivers a-blood replacement biomaterial that is cost effective and as efficacious as blood. The envisioned artificial blood will be universal, requiring no typing, will have long shelf life and will be easy to store.

描述：（逐字记录）我们计划设计、开发和生产一种经济的 基于改良分子人血红蛋白的携氧血浆扩张器 具有确保维持微血管的特性 功能，从而提高存活率和组织氧合作用 血液，用于在受伤后 48 小时内治疗创伤受害者。该计划 是垂直整合的，包括从红色生产纯化血红蛋白 通过改进的、独立的血浆分级分离血细胞 离心机 ~at 直接产生必要的分子修饰和 单位人造血液可供使用。这种方法消除了需要 制造大型、清洁的设施并降低成本。此外，它允许 适用于边远地区的生产。我们的生物工程设计原则是 当血液替代液被引入循环系统时，它会导致 由此产生的血液粘度保持足够高以确保 在血液/组织界面处产生足够的剪切应力，我们 已证明对于提供正常的毛细血管血流是必要的 组织存活的关键决定因素。根据这个原则，即使很小 一定量的无细胞血红蛋白（l-2 g/dl）对于改善病情非常有效 出血后存活。由于这种低剂量效应，至少有两个单位 可以从所采集的每个单位的正常血液中获得产品。分子 所追求的改性是用聚乙二醇进行表面改性 (PEG) 和其他会产生大半径分子的修饰。 设想了不同的产品配方，包括低容量 通过自体输血恢复血容量的浓缩溶液。这 计划涵盖人工血液生产的各个方面，从获得 最终商业产品的原材料和目的；建立 一种提供a-血液替代生物材料的输血技术 这是经济高效且像血液一样有效的方法。设想的人工 血液将是通用的，无需打字，保质期长， 会很容易储存。