Artificial blood refers to substances engineered to replicate specific functions of natural blood, primarily the transport of oxygen and carbon dioxide throughout the body. While true blood performs numerous roles, including clotting and fighting infections, artificial blood focuses on the respiratory gas exchange typically handled by red blood cells. These developed products aim to serve as a temporary substitute, offering a potential alternative to traditional blood transfusions in various medical scenarios.
The Need for Artificial Blood
The reliance on donated human blood presents several challenges that underscore the necessity for artificial blood. Chronic blood shortages are a significant issue, driven by low donor rates, natural disasters, or mass casualty events. Many low- and middle-income countries face a substantial deficit in blood supply, with about 40% of blood collected in high-income countries, which represent only about 18% of the world’s population.
Blood typing and compatibility also pose challenges, as transfusions require careful cross-matching to prevent adverse immune reactions, limiting immediate availability. The risk of transmitting infectious diseases, such as viruses and bacteria, remains a concern, particularly in regions with less robust screening infrastructures. For example, in sub-Saharan Africa, HIV, HBV, and HCV prevalence in donor blood can be significantly higher.
Natural blood has a limited shelf life, about a month, and requires strict refrigeration, complicating transport and availability in remote or emergency settings. These storage and logistical requirements contribute to wastage. Artificial blood seeks to overcome these practical limitations, offering a more stable, universally compatible, and readily available option for medical interventions.
Types of Artificial Blood Substitutes
The development of artificial blood has primarily focused on two main categories: Hemoglobin-Based Oxygen Carriers (HBOCs) and Perfluorocarbons (PFCs), alongside other emerging approaches.
Hemoglobin-Based Oxygen Carriers (HBOCs)
HBOCs are derived from natural hemoglobin, often from human or bovine blood, processed to enhance stability and reduce toxicity. These HBOCs function by directly transporting oxygen. Unlike whole blood, HBOCs are cell-free, eliminating the need for blood typing and cross-matching. However, raw hemoglobin can be toxic outside red blood cells, potentially causing vasoconstriction and elevated blood pressure.
Perfluorocarbons (PFCs)
PFCs represent a different approach, consisting of synthetic, inert molecules that can dissolve large quantities of oxygen. These clear, colorless liquids are not water-soluble and must be prepared as emulsions, often with lipids, to be suspended in the bloodstream. PFCs transport oxygen by dissolving it rather than binding it chemically. PFC particles are significantly smaller than red blood cells, potentially allowing them to deliver oxygen to tissues natural red blood cells might not reach. Advantages of PFCs include their synthetic nature and potential for large-scale, cost-effective manufacturing. While some PFC products have been approved for limited use, their lower oxygen-carrying capacity often necessitates larger volumes.
Other Approaches
Other approaches include synthetic red blood cells, such as liposome-encapsulated hemoglobin (LEH) or hemoglobin vesicles (HbV). These systems encapsulate purified hemoglobin within phospholipid vesicles, mimicking the structure of natural red blood cells. This encapsulation helps shield the hemoglobin from the body’s immune system and mitigate toxicities associated with free hemoglobin.
Current Research and Clinical Progress
The field of artificial blood involves ongoing research and various stages of clinical development. No product has yet achieved widespread clinical approval for general use in many regions, including the USA.
Research in Japan
Japan is at the forefront of this research, with Nara Medical University leading clinical trials for a synthetic, universally compatible blood substitute. Trials began administering doses to healthy adult volunteers in March 2025. This Japanese artificial blood product, hemoglobin vesicles (HbV), uses hemoglobin from expired donor blood encapsulated in lipid membranes. This design aims to replicate oxygen transport without carrying blood type antigens, making it universally applicable and virus-free. Early-stage trials in 2022 confirmed their safety and oxygen-carrying potential, with minor, self-resolving side effects reported.
Research in the United States
In the United States, research continues. ErythroMer (EM), developed by KaloCyte and the University of Maryland, is in final preclinical development, designed as a bio-synthetic nano-cyte that closely imitates red blood cell physiology. Other promising products are in advanced development, including platelet technologies like Thrombosomes from CellPhire, which are in human phase 2 trials.
While some earlier artificial oxygen carriers faced challenges and were withdrawn or did not achieve widespread success, the current focus is on developing third and fourth-generation products. These newer designs aim to overcome previous limitations by imitating the cellular structure of red blood cells more closely or by incorporating protective mechanisms. Efforts are also underway to develop dried plasma products for field deployment, with products like EZPLAZ (Teleflex) and FrontlineODP (Velico Medical) undergoing FDA approval processes and human clinical trials.
Safety and Efficacy Considerations
The journey of artificial blood substitutes from laboratory to widespread clinical adoption involves rigorous assessment of their safety and efficacy. A primary concern is the safety profile, including potential side effects such as vasoconstriction, immune reactions, and organ toxicity. Cell-free hemoglobin, if not properly modified or encapsulated, can cause high blood pressure and damage organs.
Ensuring the purity of these products and understanding their long-term effects on the human body are also ongoing areas of research. Efficacy is another factor, evaluating how well these substitutes perform the core functions of natural blood, particularly oxygen delivery and volume expansion. This includes assessing their half-life and comparability to traditional blood transfusions.
Regulatory approval processes, such as those overseen by health authorities like the FDA, are extensive and demanding, requiring comprehensive preclinical and clinical testing to demonstrate both safety and effectiveness. The manufacturing process also presents significant challenges, as large-scale production must be cost-effective and consistent to ensure affordability and accessibility.
Conversely, artificial blood products offer advantages in storage and stability. Unlike natural blood, which has a limited shelf life of about a month and requires strict refrigeration, artificial blood can often be stored for a year or more, potentially at room temperature. This extended shelf life and less stringent storage requirements could simplify logistics, making these products more readily available in emergencies or remote areas.