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）我们计划设计，开发和生产经济 基于修饰的分子人血红蛋白的氧气携带血浆扩张剂 采用可确保维持微血管的特性设计 功能，导致相对于生存率和组织氧合的提高 血液，用于在受伤后48小时内治疗创伤受害者。该程序 垂直整合，包括从红色产生纯化的血红蛋白 血细胞通过修改的自我包含的等离子分馏 离心〜在直接产生必要的分子修饰和A 人造血单位准备使用。这种方法消除了对 制造大型干净设施并降低成本。此外，它允许 用于偏远地区的生产。我们的生物工程设计原则是 当循环中引入鲜血液时，应引起 由此产生的血液粘度保持足够的升高以确保 在血管/组织界面上足够的剪切应力，我们 已经证明必须提供正常毛细血管血流 钥匙 - 组织生存的确定性。根据这个原则甚至很小 无细胞的血红蛋白量（L-2 g/dl）在改善中非常有效 出血后的生存。由于这种低剂量效应至少两个单位 可以从每个收集的正常血液中获得产物。分子 要追求的修改是用聚乙烯乙二醇进行表面修饰 （PEG）和其他将导致半径较大的分子的修饰。 设想产品的不同配方包括低容量 浓缩溶液将通过自动输血来恢复血液量。这 程序涵盖了人造血液产生的各个方面 最终商业产品的原材料，目的是；建立 输血技术，可提供a-llood替代生物材料 这是具有成本效益的，并且像血一样有效。设想的人造 血液将是普遍的，不需要打字，将具有很长的保质期，并且 很容易存储。