Заменители крови: история, разработка и перспективы.

Substance that is used in place of biological blood
the rugby union and rugby league term

A blood substitute (also called artificial blood or blood surrogate) is a substance used to mimic and fulfill some functions of biological blood. It aims to provide an alternative to blood transfusion, which is transferring blood or blood based products from one person into another. Thus far, there are no well accepted oxygen carrying blood substitutes, which is the typical objective of a red blood cell transfusion; however, there are widely available non blood volume expanders for cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah's Witnesses and others who have religious objections to receiving transfused blood. The main categories of "oxygen carrying" blood substitutes being pursued are hemoglobin based oxygen carriers (HBOC) Oxygen therapeutics are in clinical trials in the U. S. and European Union, and Hemopure is available in South Africa.

After William Harvey discovered blood pathways in 1616, many people tried to use fluids such as beer, urine, milk, and non human animal blood as blood substitute. Sir Christopher Wren suggested wine and opium as blood substitute. At the beginning of the 20th century, the development of modern transfusion medicine initiated through the work of Landsteiner and co authors opened the possibility to understanding the general principle of blood group serology. Simultaneously, significant progress was made in the fields of heart and circulation physiology as well as in the understanding of the mechanism of oxygen transport and tissue oxygenation. Restrictions in applied transfusion medicine, especially in disaster situations such as World War II, laid the grounds for accelerated research in the field of blood substitutes. Early attempts and optimism in developing blood substitutes were very quickly confronted with significant side effects, which could not be promptly eliminated due to the level of knowledge and technology available at that time. The emergence of HIV in the 1980s renewed impetus for development of infection safe blood substitutes. The continuous decline of blood donation combined with the increased demand for blood transfusion (increased ageing of population, increased incidence of invasive diagnostic, chemotherapy and extensive surgical interventions, terror attacks, international military conflicts) and positive estimation of investors in biotechnology branch made for a positive environment for further development of blood substitutes. In 2023, DARPA announced funding twelve universities and labs for synthetic blood research. Human trials would be expected to happen between 2028 2030.

Haemoglobin is the main component of red blood cells, comprising about 33% of the cell mass. Haemoglobin based products are called haemoglobin based oxygen carriers (HBOCs). Efforts to overcome this toxicity have included making genetically engineered versions, cross linking, polymerization, and encapsulation. Hemolink (Hemosol Inc., Mississauga, Canada) was a haemoglobin solution that contained cross linked an o rafinose polymerised human haemoglobin. and declared bankruptcy in 2005. Hemopure was developed by Biopure Corp and was a chemically stabilized, cross linked bovine (cow) haemoglobin in a salt solution intended for human use; the company developed the same product under the trade name Oxyglobin for veterinary use in dogs. Oxyglobin was approved in the US and Europe and was introduced to veterinary clinics and hospitals in March 1998. Hemopure was approved in South Africa and Russia. Biopure filed for bankruptcy protection in 2009. Its assets were subsequently purchased by HbO2 Therapeutics in 2014. PolyHeme was developed over 20 years by Northfield Laboratories and began as a military project following the Vietnam War. It is human haemoglobin, extracted from red blood cells, then polymerized, then incorporated into an electrolyte solution. In April 2009, the FDA rejected Northfield's Biologic License Application and in June 2009, Northfield filed for bankruptcy. Dextran Haemoglobin was developed by Dextro Sang Corp as a veterinary product, and was a conjugate of the polymer dextran with human haemoglobin. Hemotech was developed by HemoBiotech and was a chemically modified haemoglobin. Somatogen developed a genetically engineered and crosslinked tetramer it called Optro. It failed in a phase II trial and development was halted. which led to Curacyte shutting down. Similarly, Hemospan was developed by Sangart, and was a pegylated haemoglobin provided in a powdered form. While early trials were promising Sangart ran out of funding and closed down. describes a large scale ex vivo production of mature human blood cells using hematopoietic stem cells. The cultured cells possessed the same haemoglobin content and morphology as native red blood cells. The authors contend that the cells had a near normal lifespan, when compared to natural red blood cells. Scientists from the experimental arm of the United States Department of Defense began creating artificial blood for use in remote areas and transfuse blood to wounded soldiers more quickly in 2010. The blood is made from the hematopoietic stem cells removed from the umbilical cord between human mother and newborn using a method called blood pharming. Pharming has been used in the past on animals and plants to create medical substances in large quantities. Each cord can produce approximately 20 units of blood. The blood is being produced for the Defense Advanced Research Projects Agency by Arteriocyte. The Food and Drug Administration has examined and approved the safety of this blood from previously submitted O negative blood. Using this particular artificial blood will reduce the costs per unit of blood from $5,000 to equal or less than $1,000.