Advancements in artificial blood research target to enhance product safety and effectiveness.

Researchers have made great strides in ensuring that red blood cell substitutes – or synthetic blood – are able to work safely and effectively when infused into the bloodstream.

The key is to make the synthetic blood molecules large enough that they don’t leak from blood vessels into tissues and cause dangerous cardiovascular side effects, suggests a new study led by researchers from Ohio State University.

Although blood loss is usually treated with transfusions of donated blood units, in cases where blood transfusions are not readily available or time is very limited to check a patient’s blood type compatibility (such as in certain rural areas or on the battlefield) Artificial blood products offer medical professionals more flexibility in treatment. In clinical trials, previous generations of these blood substitutes often led to many poor health outcomes, with individuals experiencing symptoms ranging from narrowed blood vessels and high blood pressure to tissue injury.

In this study, the researchers found that a specific fraction of red blood cell substitutes can provide a range of health benefits, and can reduce the risk of cardiovascular side effects – if its components are in the right size.

“We found that as you increase the size of your red blood cell replacement molecules, you have fewer side effects,” said Alisyn Greenfield, PhD, lead author of the study. Student in Chemical and Biological Molecular Engineering at Ohio State. “There is even a certain size range that has better benefits when it comes to the kind of cardiovascular effects seen with previous generations of these materials.”

Their findings have been published in the journal Biomolecules.

The researchers tested a substitute for red blood cells called polymerized human hemoglobin – PolyhHb. Although earlier commercial versions were explored in clinical settings, they did not receive FDA approval due to their many side effects.

To find a better solution, the team focused on defining the targeted therapeutic volume of PolyhHb by synthesizing the material into four differently sized arches and exploring the cardiovascular response in guinea pig models. The results showed that the larger braces did not slip out of the blood vessels, or cause blood vessels to narrow, leading to high blood pressure.

The antioxidant status of guinea pigs is more similar to humans than to other rodents, said senior study author Andre Palmer, a professor of chemical and biochemical engineering at Ohio State, making them a good model to study.

While these red blood cell substitutes are not intended to completely replace blood, this research highlights the potential of these substances. If it is given to a person soon after infection, Palmer said, it can be used to buy enough time to get the person to a medical facility to receive a blood transfusion.

In addition, because blood substitutes are not made with any surface antigens or markers on the outside of the red blood cell membrane, they can be transfused to anyone, regardless of blood type. However, artificial blood is still a long way from commercialization.

Palmer said that although it can be stored at room temperature for several years compared to the 42-day storage period for donated blood, synthetic blood does not come close to replicating the lifespan of real blood cells. Once a typical red blood cell has been produced, it circulates in the human body for about 120 days, however the substances in current blood substitutes are made with a half-life of about 24 hours after ingestion.

More study is needed to more accurately determine the safety and efficacy of red blood cell substitutes in clinical settings. “By conducting this study, we demonstrated that we can improve on what currently exists, and we hope to be able to advance our research and translate these materials into the clinic,” said Greenfield.