Advancing the science and engineering of artificial blood
The U.S. blood supply is at risk due to the presence of emerging infectious diseases such as COVID-19 and reduced donation rates.
Therefore, the development of safe and effective blood substitutes for use in transfusion medicine could significantly improve the emergency treatment of accident victims and wounded soldiers, as well as patients undergoing surgery, especially when blood is in short supply.
Professor Andre Palmer has invested 20 years of his career researching in this critical area supported by several federal grants. Working with fellow Chemical and Biomolecular Engineering Professor David Wood, Palmer has earned a four-year, $2.7 million grant from the National Institutes of Health (NIH) to develop safer, chemically well-defined red blood cell (RBC) substitutes that could help save lives.
While blood substitutes are not meant to be a permanent replacement for whole blood, which serves many different functions, the advantages of artificial RBCs are significant. They can be used universally by people with any blood type and are stable at ambient temperatures up to several years without loss of activity, whereas human RBCs have to be discarded after 42 days of cold storage. RBC substitutes also are free of new, unidentified pathogens that can unwittingly be passed on to patients, as had happened before the AIDS, Zika and H1N1 viruses were discovered.
Based on previous research, Palmer’s polymerized hemoglobin (PolyHb) RBC substitute has shown promise in stabilizing hemorrhage through administration of less than half the volume of lost blood in small animals.
His current project with Wood focuses on precisely engineering the size and shape of PolyHb molecules. Some recent clinical trial results from companies commercializing their own PolyHb solutions have shown some concerning side effects including vasoconstriction, hypertension and oxidative tissue damage. Palmer and Wood hypothesize that the broad size distributions of these commercial products may have a negative impact. To determine how individual components of complex PolyHb mixtures interact with the vasculature, the team will engineer and evaluate molecularly uniform, monodisperse, and high molecular weight PolyHb nanostructures for use in transfusion medicine as RBC substitutes.
“This work will shed more light on the mechanisms underlying PolyHb toxicity and identify strategies to counteract these side effects,” explained Palmer.
To complete this work, Wood will develop a method for assembling single hemoglobin molecules into larger structures through the use of protein splicing. This method allows precise assembly of several molecules into larger structures, allowing Wood and his students to design and produce different PolyHb structures with uniform shapes and sizes.
“This level of precision in protein engineering will allow new insights into the mechanisms by which currently-available PolyHb therapeutics yield both positive and negative patient outcomes,” said Wood.
In 2018, Palmer secured a $2.4 million U.S. Army Medical Research and Materiel Command grant to develop a resuscitation therapy to treat life-threatening hemorrhage on the battlefield.
This research is supported by the National Heart, Lung, And Blood Institute of the NIH under Award Number R01HL156526. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
