BIOENGINEERING DESIGN OF ARTIFICIAL BLOOD

描述：(逐字)我们计划设计、开发和生产一种经济的 基于修饰分子人血红蛋白的载氧血浆扩张器 具有确保微血管维持的特性 功能，从而改善存活率和组织氧合 血液，用于创伤受害者受伤后48小时内的治疗。该计划 是垂直整合的，包括从红色中生产纯化的血红蛋白 血细胞通过改良的自含式血浆分离 离心机直接产生必要的分子修饰和一种 可供使用的人造血单位。这种方法不再需要 制造大型、清洁的设施并降低成本。此外，它还允许 用于偏远地区的生产。我们的生物工程设计原则是 当血液置换液被引入循环时，它应该会导致 由此产生的血液粘度保持足够高的水平，以确保 在血液/组织界面产生足够的剪应力，我们 已经证明了提供正常的毛细血管血流是必要的 关键-组织存活的决定因素。根据这一原则，即使是小的 大量的游离血红蛋白(L-2g/dl)对改善 出血后存活。由于这种低剂量效应，至少有两个单位的 产品可以从每单位采集的正常血液中获得。分子 要进行的改性是用聚乙二醇改性表面。 (Peg)，以及其他将导致大半径分子的修饰。 设想了不同的产品配方，包括低容量 通过自体输血恢复血量的浓缩液。这个 该计划涵盖了人工血液生产的方方面面，从获得 将原材料转化为最终的商业产品并以此为目标； 一种提供A型血液替代生物材料的输血技术 这是具有成本效益的，而且像血液一样有效。想象中的人造世界 血液将是通用的，不需要打字，将有很长的保质期和 将很容易存储。

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.