Researchers have made huge strides to ensure that red blood cell substitutes – or artificial blood – are able to work safely and effectively when transfused into the bloodstream.
The key is to make artificial blood molecules large enough that they don’t leak from blood vessels into tissues and cause dangerous cardiovascular side effects, notes a new study by researchers at Ohio State University. .
Although blood loss is usually treated by transfusing units of donated blood, in cases where transfusions are not readily available or time is too limited to screen the patient’s blood group compatibility (such as in some rural areas or on the battlefield), artificial blood products offer healthcare professionals more flexibility for treatment. In clinical trials, previous generations of these blood substitutes often resulted in several health issues, as individuals experienced symptoms ranging from narrowed blood vessels and high blood pressure to tissue damage.
In this study, researchers found that a certain fraction of red blood cell substitute may provide a range of health benefits and may reduce the risk of cardiovascular side effects – if its components are the right size.
“We found that when you enlarge the red blood cell surrogate molecules, you have fewer side effects,” said Alisyn Greenfield, the study’s lead author and a doctoral candidate in chemical and biomolecular engineering at Ohio State. “There is even a particular size range that has better benefits when it comes to the kind of cardiovascular effects seen with previous generations of this material. »
Their findings were published in the journal Biomacromolecules.
The researchers tested a red blood cell substitute called polymerized human hemoglobin — PolyhHb. Although earlier commercial versions have been explored in the clinical setting, they have not received FDA approval due to their numerous side effects.
To find a better solution, the team focused on identifying a target therapeutic size of PolyhHb by synthesizing material in four different sized carriers and exploring the cardiovascular response in guinea pig models. The results showed that the larger hooks did not leak out of blood vessels or cause blood vessels to narrow and did not cause high blood pressure.
The study’s lead author, Andre Palmer, a professor of chemical and biochemical engineering at Ohio State, said the antioxidant status of guinea pigs is more similar to humans than that of other rodents, making them a good model for study.
Although these red blood cell substitutes are not intended to replace blood entirely, this research highlights the potential of these materials. If transfused to a person soon after an injury, they could be used to buy the person enough time to be transported to a medical facility to receive a blood transfusion, Palmer said.
Additionally, since blood substitutes do not contain any surface antigens or markers outside of the red blood cell membrane, they can be transfused to anyone, regardless of their blood type. That said, artificial blood is still far from being commercialized.
Although it can be stored at room temperature for several years compared to the 42-day storage period for donated blood, artificial blood falls far short of replicating the lifespan of real blood cells, Palmer said. Once produced, a typical red blood cell circulates in the human body for a period of about 120 days, but current blood substitute materials are made with only a half-life of about 24 hours after administration.
Further study is needed to more accurately determine the safety and effectiveness of red blood cell substitute in the clinical setting. “By doing this study, we have demonstrated that we can improve on what currently exists and hopefully be able to advance our research and translate these materials into the clinic,” Greenfield said.
This study was supported by the National Institutes of Health. Other co-authors from Ohio State were Xiangming Gu, Ahmad Yahya, Amid Vahedi, and Mohd. Asim Khan. Other co-authors came from the University of Maryland.
