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，开发和生产一个经济的 基于修饰分子人血红蛋白的携氧血浆扩张剂 具有确保维持微血管 功能，从而改善生存和组织氧合， 血液，用于在受伤后48小时内治疗创伤受害者。程序 垂直整合，包括从红细胞中生产纯化的血红蛋白 通过改良的自含式血浆分离法分离血细胞 离心机直接产生必要的分子修饰， 一个单位的人造血液准备使用。这种方法消除了对 制造大型清洁设施并降低成本。此外，它允许 在偏远地区生产。我们的生物工程设计原则是， 当血液置换液被引入循环系统时 所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， 已经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。根据这一原则，即使很小 一定量的无细胞血红蛋白（1 - 2g/dl）对于改善 出血后存活率由于这种低剂量效应， 产品可以从采集的每个单位的正常血液中获得。分子 进行的改性是用聚乙二醇进行表面改性 (PEG)，以及将导致具有大半径的分子的其他修饰。 设想了不同的产品制剂，包括低体积的 通过自体输血来恢复血容量的浓缩溶液。的 该计划涵盖了人工血液生产的所有方面，从获得 将原材料转化为最终商业产品，旨在： 一种输血技术， 这是成本效益和血液一样有效。所设想的人工 血液将是通用的，不需要分型，将有很长的保质期， 将易于存储。