The goal of creating a complete, synthetic replacement for human blood is a long-standing pursuit in medicine, but a true “artificial blood” that perfectly mimics every function of the body’s natural fluid does not currently exist. The materials developed so far are more accurately termed “blood substitutes” or “oxygen therapeutics,” designed primarily to replicate the red blood cell’s ability to transport oxygen. These substitutes offer the potential for universal compatibility, long shelf life, and freedom from infectious disease risk. However, they remain limited in their ability to perform the full array of complex biological tasks carried out by whole blood. Current research focuses on creating a product that can be safely and widely used in trauma and surgical settings.
Limitations of Donated Blood
The complex reliance on human donors presents significant logistical and safety challenges for maintaining a stable blood supply. Donated red blood cells have a relatively short shelf life, typically limited to 42 days, which necessitates a constant, rigorous collection and distribution cycle to prevent shortages. Other components, such as platelets, are even more perishable, often lasting only about five to seven days before they expire.
Compatibility testing adds complexity to transfusions, requiring careful matching of A, B, and Rh antigens to avoid severe immune reactions. Every unit of donated blood must also undergo extensive screening for communicable diseases like HIV and hepatitis, which adds time and cost to the supply chain. These constraints—perishability, compatibility requirements, and pathogen risk—motivate the development of synthetic alternatives that can be stored at room temperature and administered universally.
Existing Oxygen-Carrying Substitutes
Current research focuses on two main classes of cell-free oxygen carriers designed to bypass the limitations of donor blood. These substitutes function as oxygen therapeutics capable of transporting gas to tissues, but they are not whole blood replacements. They are advantageous because they do not require blood-type matching and can be sterilized to eliminate the risk of disease transmission.
Hemoglobin-Based Oxygen Carriers (HBOCs)
HBOCs utilize modified hemoglobin, often derived from human or bovine sources, which is chemically stabilized through cross-linking or polymerization. This modification is necessary because uncontained hemoglobin is toxic; it can damage the kidneys and scavenge nitric oxide (NO) from blood vessel walls. Scavenging NO, a molecule that helps relax blood vessels, can lead to unwanted side effects such as vasoconstriction and a rise in blood pressure.
Perfluorocarbons (PFCs)
PFCs are synthetic, chemically inert liquids composed of carbon and fluorine atoms. PFCs dissolve large quantities of gas, but this mechanism requires the patient to be breathing high concentrations of oxygen for the substitute to be effective. Since PFCs are immiscible with water, they must be processed into a stabilized emulsion for intravenous injection. While their small particle size allows them to perfuse into capillaries, they typically have a low oxygen-carrying capacity compared to natural blood.
What True Artificial Blood Still Lacks
Despite their ability to carry oxygen, current substitutes fall short of being a true artificial blood because they cannot replicate the complex functions of whole blood. Whole blood is a dynamic fluid containing cellular and protein components responsible for far more than just gas transport. For instance, none of the existing oxygen carriers can stop bleeding because they lack platelets and the intricate cascade of plasma clotting factors necessary for hemostasis.
Artificial substitutes also do not contain white blood cells, the specialized leukocytes that form the foundation of the body’s immune system for fighting infection and surveillance. Plasma, the liquid component of blood, contains proteins like albumin that maintain osmotic pressure and fluid balance within the circulatory system. This function is largely absent in HBOCs and PFCs.
While oxygen therapeutics can sustain life temporarily in an emergency, they are limited to short-term applications and cannot replace the multifaceted roles of whole blood. They serve only as temporary oxygen bridges until a patient can receive a traditional blood transfusion.
Future Research and Clinical Status
The next generation of research is moving beyond simple oxygen carriers toward developing laboratory-grown blood components using stem cell technology. Scientists are working with induced pluripotent stem cells (iPSCs) or hematopoietic stem cells to manufacture functional red blood cells in bioreactors. This approach promises to produce universal donor blood, such as O-negative, that is consistently fresh, pathogen-free, and potentially more effective for chronic transfusion patients.
While clinical trials administering lab-grown red blood cells have begun, the technology faces significant hurdles, primarily in scaling production. It is currently difficult and expensive to produce the massive quantities needed for widespread clinical use, limiting its viability to patients with rare blood types or complex transfusion needs. Regulatory approval is another major challenge, as any new blood product must undergo extensive and costly clinical trials to demonstrate long-term safety before it can be adopted into general medical practice.