Blood substitute

A blood substitute (also called artificial blood or blood surrogate) is a substance used to mimic and fulfill some functions of biological blood. In some cases, it can serve as an alternative to blood transfusion, a therapy using donated blood or blood-based products.

When referring to blood substitutes that are oxygen-carrying, the term oxygen therapeutics is increasingly used to emphasize their intended primary use in treating severe anemia. Such blood substitutes must compensate for oxygen's poor solubility, due to which dissolved oxygen typically accounts for only a fraction of oxygen transport; in humans, hemoglobin is the most important oxygen carrier. There are two categories of oxygen-carrying blood substitutes being pursued: hemoglobin-based oxygen carriers (HBOC) and perfluorocarbon-based products. As of yet, there are no standard oxygen therapeutics in use internationally, although in various countries several enjoy limited approval for specific applications or are undergoing clinical trials.

For centuries, an assortment of different fluids were used as blood substitutes, including beer, plant resins, non-human blood, and human urine. Where blood transfusion was practiced, unpredictable, fatal reactions sometimes occurred (now identified as hemolytic reactions to transfusion). While there were developments in the area, such as William Harvey's description of the blood circulation system in the early 17th century and significant advances in the understanding of the mechanism of oxygen transport and tissue oxygenation in the 18th and 19th centuries, the idea of blood types was only introduced at the beginning of the 20th century by Karl Landsteiner. In many instances physicians thus sought to find less-risky alternatives, resulting in experiments such as the 1870s transfusion of milk in the United States.

Research into blood substitutes to replace blood transfusion has been driven by several factors in recent years. The emergence of HIV and discovery of mad cow disease in the 1980s brought fresh concerns over blood product safety. Additionally, blood shortages have become increasingly common, even where well-established systems exist. The constraints of blood storage, including a limited shelf-life and need for constant refrigeration, make its transport difficult.

In 2023, DARPA announced funding for twelve universities and labs for synthetic blood research. Human trials would be expected to happen between 2028 and 2030.

Efforts have focused on molecules that can carry oxygen, and most work has focused on recombinant hemoglobin, which normally carries oxygen, and perfluorocarbons (PFC), chemical compounds which can carry and release oxygen.

The first approved oxygen-carrying blood substitute was a perfluorocarbon-based product called Fluosol-DA-20, manufactured by Green Cross of Japan. It was approved by the Food and Drug Administration (FDA) in 1989. Because of limited success, complexity of use and side effects, it was withdrawn in 1994. However, Fluosol-DA remains the only oxygen therapeutic ever fully approved by the FDA. As of 2017, no hemoglobin-based product had been approved.

Perfluorochemicals are not water soluble and will not mix with blood, therefore emulsions must be made by dispersing small drops of PFC in water. This liquid is then mixed with antibiotics, vitamins, nutrients and salts, producing a mixture that contains about 80 different components, and performs many of the vital functions of natural blood. PFC particles are about ⁠1/40⁠ the size of the diameter of a red blood cell (RBC). This small size can enable PFC particles to traverse capillaries through which no RBCs are flowing. In theory this can benefit damaged, blood-starved tissue, which conventional red cells cannot reach. PFC solutions can carry oxygen so well that mammals including humans, can survive breathing liquid PFC solution, called liquid breathing.^{[citation needed]}