Materials Biotechnology and Blood Substitutes
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Materials Biotechnology and Blood Substitutes Nir Kossovsky and David Millett A Médical Mission Blood is a dispersion of formed éléments in an aqueous colloid. The combined mass of the formed éléments of blood measure on average 30 ml per kg body weight, or about the same weight as the liver.1 The colloidal phase of blood contains numerous organic factors that play important primary and supporting rôles in homeostasis, including immune surveillance, coagulation, and nutrient transport. Erythrocytes (red blood cells) are the principle formed éléments and provide the life-sustaining function, in conjunction with the heart, lungs, blood vessels and kidneys, of transporting and protecting the oxygen-carrying pigment, hemoglobin, to the tissues. The oxygen-binding properties of hemoglobin are sensitive to factors such as the coopérative effects of 0 2 binding, pH and CÔ2 levels, and the présence of other metabolic intermediates such as 2,3-diphosphoglycerate. The synergistic effects of thèse factors produce a wellknown sigmoidal curve plot of the relationship between oxygen affinity and the partial pressure of oxygen (p0 2 ): there is high oxygen affinity in the lung where the p 0 2 is high, and a low oxygen affinity in the tissues, where the p0 2 is low. Uptake and delivery of oxygen by hemoglobin is associated with considérable spatial rearrangement of the hemoglobin molécule.2 Blood is a non-Newtonian suspension. Its viscosity is a function of both the vascular diameter and the concentration of erythrocytes. At a normal hematocrit of 40%, the viscosity of blood ranges between 2 and 4 Pa • s as measured in tubes ranging 10-1,500 /xm diameter. The osmolarity of blood sérum is 275-295 mOsm/1. The need for blood replacement for trauma/emergency resuscitation or volumetric exchange during major surgical opérations occurs when an individual loses more than 1,000 cm3 of blood or about 20-
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25% of the circulating volume.3 The need for exogenous sources of blood has been partly alleviated by advancing technologies in blood conservation and public health éducation promoting the storage of autologous blood. Nevertheless, a number of difficulties remain in testing and securing autologous blood resources, and the présent risks of transmitting blood-borne viruses, including the hepatitis viruses and human immunodeficiency virus, hâve renewed interest in developing safe and effective blood substitutes. Idéal Blood Substitute As presently envisioned, an idéal blood substitute would satisfy a number of operational needs. In addition to physiological oxygen-carrying properties, blood substitutes would be expected to exhibit universal transfusability, viscosity and colloid osmotic characteristics similar to natural blood, the absence of biological rétention (trapping) in blood-filtering organs associated with a measurable life of plasma circulation, the absence of organ toxicity, sterility, a "reasonable" shelf life, and ease and cost effectiveness in production. Three major technologies are being examined for their suitability as
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