When was artificial blood invented

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The cross-linked hemoglobin molecules are stable and do not break down. Some bifunctional agents can also cross-link each hemoglobin molecule internally to prevent its breakdown into dimers.

Recombinant technology applied to the bacterium E. Hemoglobin can also be cross-linked to soluble polymers to form so-called conjugated hemoglobin. All the above modifications also result in blood substitutes that have a greater ability to release oxygen to the tissues than do red blood cells. These procedures remove microorganisms responsible for diseases such as AIDS and hepatitis. Because the substitutes do not have cell membranes with blood-group antigens, cross-matching and typing are not required before use.

This saves time and facilities and allows on-the-spot transfusion. Furthermore, blood substitutes can be stored for more than one year, as compared with about one month for donor blood stored using standard methods.

Thus, their present role is restricted to short-term applications. For example, substitutes are being tested in humans for replacing blood lost during some cardiac, cancer, orthopedic and trauma surgeries. Another promising application is to ameliorate the effects of severe bleeding in traumatic injuries from accidents, disasters or wars.

In the case of polyhemoglobin, Northfield is now in Phase III large-scale efficacy clinical trials that infuse up to 5, milliliters of blood substitutes into surgical patients.

The company is using pyridoxalated glutaraldehyde cross-linked human hemoglobin. Biopure is in Phase II small-scale efficacy clinical trials using pyridoxalated glutaraldehyde cross-linked bovine hemoglobin. Hemosol is in Phase II clinical trials in surgical patients, using a new cross-linker to form a molecule known as o-raffinose cross-linked human polyhemoglobin.

In the case of intramolecularly cross-linked hemoglobin, Baxter is now in Phase III clinical trials in a large number of surgical patients; the company is using Diaspirin cross-linked human hemoglobin. Somatogen is now deep into their Phase II clinical trials with their recombinant human hemoglobin. Chang in Science, Vol. Bunn and J. Concentrated efforts to develop blood substitutes for public use only seriously started after because of public concerns regarding HIV in donor blood.

Unfortunately, a product must undergo years of research and development followed by clinical trials before it is ready for use in patients. It will take at least another one to two years for blood substitutes to be available for routine use. Had there been a serious development effort in the s, blood substitutes would have already been available in As it is, the public has continued to be exposed to the potential, though extremely rare, hazard of HIV in donor blood.

They also do not have the enzymes needed to protect the body against oxidants such as oxygen radicals. Unchecked, oxygen radicals may cause reperfusion injuries and other problems.

Enzymes are also important in preventing hemoglobin from being oxidized to methemoglobin, which cannot carry oxygen. Researchers are studying ways to solve this problem, including cross-linking the required enzymes to hemoglobin or further modifying the molecular structure of hemoglobin.

These advances will appear in second-generation blood substitutes. Thus, researchers are working on more complicated, third-generation blood substitutes that will encapsulate hemoglobin and the required enzymes inside artificial red blood cells. One method is to encapsulate hemoglobin inside lipid vesicles about 0.

This technique also increases the circulation time. A more recent approach is to use nanotechnology to encapsulate hemoglobin and enzymes inside biodegradable polylactic acid membrane nanocapsules some 0. Yet researchers are now facing many of the same problems as in the s and s. Soon after, Lower transfused lamb blood into a clergyman animal blood transfusions would eventually be outlawed, but not until the end of the 17th century.

One hundred years after that, Philadelphia physician Dr. Further experiments quickly followed, and within decades of that initial blood exchange, a British obstetrician saved a life with the procedure. While the quest for blood substitutes goes back centuries, true progress, however, has only been made in recent decades. In , biochemist Leland Clark first demonstrated the oxygen-carrying abilities of perfluorochemicals PFC.

These liquid compounds are often used for coatings in products like furniture, food packaging, and electrical wire insulation. Clark and others found droplets of perfluorochemicals could capture and transport dissolved oxygen in its liquid core, albeit not as efficiently as hemoglobin. In the s and s, a number of physicians attempted to use PFC emulsions as blood substitutes, but subsequent clinical trials demonstrated patients developed severe side effects including increased risk of stroke, low platelet count, and flu-like symptoms.

The most successful strategy has been a pursuit of hemoglobin-based blood substitutes, or HBOCs as they are called, that mimic the oxygen transport functioning of red blood cells by synthetically creating and packaging human or cow hemoglobin. HBOCs though, have a perilous past. The treatment wreaked renal havoc on their feline subjects, but efforts continued, and in a group even performed human clinical trials of this artificial hemoglobin solution; the trial led to serious kidney dysfunction in 5 of the 14 patient subjects.

By the s, a handful of researchers from Illinois to Cambridge began testing new, chemically-modified HBOCs in humans with military funding. None would even come close to FDA approval. At first, the future seemed bright for Hemopure, but safety and health concerns cut short any optimism. One study in particular analyzed 16 HBOC clinical trials and described a three-fold increase in the risk of heart attacks in people who received the substitutes compared to those who were given donor blood.

It was a major blow for research studies on artificial blood and by , investors had fled. Blood remained as mysterious an elixir as ever. Dipanjan Pan, a bioengineering professor at the University of Illinois. The synthetic polymer coating appears to solve these issues, according to Doctor. The coating is designed to respond to changes in blood pH, so the cells are programmed to pick up oxygen in the lungs — where pH is high — and let it go where in places with low oxygen — where pH is low.

The result is a product that can be freeze-dried as a powder and could be used on ships, battlefields, or even in space.

The synthetic cells are immune silent, meaning they can be used with any blood type, and can be stored at room temperature and mixed with water, ready for immediate use anywhere. Doctor says the blood powder — ErythroMer — extends transfusion therapy to many challenging locations, including warzones.

For U. Powdered blood could be carried on helicopters or ambulances and used to buy necessary time to get a wounded soldier to a medical center, where he or she could receive transfusions. Patients would still need other blood: typical blood cells circulate in the body for about four months, and the artificial blood cells only last a few days.

Doctor says he has not yet designed the packaging, but he envisions a partitioned bag with dry Erythromer and sterile water that can be popped open easily by hand and then mixed.

The powder, which looks like paprika, may also be useful in resource-limited countries where it is difficult to provide adequate blood banking or develop a stable donor pool, Doctor says. It sounds fantastic, but the revolution in blood may take some time. ErythroMer has been tested in mice, and is now in testing in larger animals. Doctor says he hopes the product will enter human trials within a decade. Right now, there are no accepted oxygen-carrying blood substitutes available for use in the U.