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Artificial Blood: Life-Saving Science

Shrewsbury, MA

We have traveled to Mars, made working artificial hearts, explored the deepest depths of the Mariana Trench, and sequenced the human genome, and yet, we haven’t been able to make artificial blood. So why haven’t we done this yet? What is stopping us? The answer to these questions lies in our blood (literally). In this article, let’s talk about what artificial blood is, why we haven’t been able to make it, and some of our current ideas.


First up, let’s get an idea of what blood actually is. Blood is a special type of connective

Red Blood Cells, RBCs, Blood, Red, Blood Cells, Bioncave
Red Blood Cells (RBCs)

tissue that is composed of white blood cells (WBCs), red blood cells (RBCs), platelets, and plasma. It has a variety of functions in the body, which include the transportation of oxygen and nutrients, blood clotting, immune defense, waste removal, and so on. Without our blood, we would just be a lump of lifeless, functionless organs.





But as amazing and life-giving as blood is, it’s not a perfect product. First, there’s the issue of shelf life: Red blood cells, or blood in general, can usually only be stored for up to 42 days, if refrigerated, after which they should no longer be transfused to patients due to decreased efficacy. Then there’s the issue of needing the right blood type when transfusing blood to a patient, as giving the wrong type can be potentially life-threatening. However, the right blood type may or may not be readily available. And, of course, the biggest issue is blood supply — that is, whether any blood is even available at all. The COVID-19 pandemic came around and just added insult to injury, worsening these blood shortages terribly. Now, roughly one in seven hospital patients need blood, which equates to about 30,000 red cell units needed in only the U.S. each day. Imagine how much blood we would need for the whole world. It’s a tall order to fill, and finding enough volunteer donors to meet that need has been and continues to be a real challenge.


We need a solution to this problem. And that’s where artificial blood comes in. Artificial blood is a product made in the lab whose goal is to act as a substitute for red blood cells. So we need artificial blood or even a blood substitute. So why haven’t we made one yet? The real reason is that blood is made of many complex parts that serve specific functions. It's tough to reproduce and match each to do their functions properly. For example, let’s say we’ve made a substitute just for the transporting oxygen function of blood. Then what about all the other functions of blood?


Blood, Blood Types, O positive, Blood Transfusion
Blood Types (In this case, O)

Along with this comes the blood type problem. Even if this new substance works, it may cause immune reactions in people with certain blood types. Not only this, but patients have diverse medical conditions, and designing an artificial blood product that caters to various health situations can be difficult. Along with this comes the problem of shelf life. Even if we develop a blood substitute, it needs to be stored for extended periods without deterioration so that we can use it when needed. There are many more challenges; this article would never end if I listed all the problems. So what are the solutions to this problem? Well, scientists have been trying to mimic blood so that we can have an alternative. We have been doing this since 1616 when someone named William Harvey started to shed light on this matter.


The ideal artificial blood product should have the following characteristics. First, it must be safe to use and compatible with the human body. This means that different blood types should not matter when artificial blood is used. This is because it shouldn’t take time just to match the blood types at certain times when blood is quickly needed. This also means that artificial blood can be processed to remove all disease-causing agents such as viruses and microorganisms. Second, it must be able to transport ample amounts of oxygen throughout the body and release it where it is needed. Third, it must be shelf-stable. Unlike donated blood, artificial blood might be stored for over a year or more. This is in contrast to natural blood which can only be stored for one month before it breaks down. Two significantly different products are currently under development as blood substitutes. They differ primarily in the way that they carry oxygen. The next two paragraphs will go into depth about those substances.


Scientists have come up with certain substances that are believed to potentially be a blood substitute. The first is our very own hemoglobin. Hemoglobin is a substance in our blood that carries oxygen from the lungs to the other tissues in the body. Artificial blood based on hemoglobin takes advantage of this natural function. These are called hemoglobin-based oxygen-carrying (HBOC) agents. These HBOC products are different than whole blood because they are not contained in a membrane, so the problem of blood typing is

Hemoglobin, Structure, Hemoglobin structure, Protein, blue, green
The Structure of Hemoglobin

eliminated. However, we have just a teeny problem. Raw hemoglobin cannot be used because it would break down into smaller, toxic compounds within the body. There are also problems with the stability of hemoglobin in a solution. Hemoglobin by itself is highly reactive because RBC-free hemoglobin in the absence of certain proteins (accustomed with RBCs) is an extremely inefficient O2 transporter, capable of off-loading only a very small amount of O2 to the tissues. Because of this highly reactive and toxic nature of cell-free hemoglobin as well as the necessary presence of certain proteins, the development of HBOCs has been quite challenging. Yet, the successful development of an HBOC blood substitute is quite advantageous because crossmatching is not required before infusion, it can be sterilized by ultrafiltration and low heat to inactivate infectious agents, and could have a long shelf life, none of which are characteristic of other RBC products.


Another common blood substitute scientists are looking into is Perfluorocarbons (PFCs). PFCs are a type of synthetic molecule composed of mainly carbon and fluorine atoms. PFCs are being investigated because they can dissolve about 10 times more oxygen than normal blood. This is good news because the main purpose that doctors want artificial blood to serve. Not only this, but PFCs can be made from renewable sources such as plant oils, making PFCs a very sustainable option. But, all that glitters is (sadly) not gold. PFCs have

PFCs, perfluorocarbons, structure, PFC structure, gray
The structure of PFCs

two significant hurdles to overcome before they can be utilized as artificial blood. First, they are hydrophobic. This means that they are not soluble in water. This is a huge problem because about 50% of our blood is water. To take care of this, scientists have to combine PFCs with something called emulsifiers to help the PFCs be suspended in the blood. Another downside to PFCs is that even though they can dissolve so much oxygen, they can’t give it away to other organs, which is the most important function of blood. Because of that, scientists have to prescribe more of the PFCs just to provide a small amount of oxygen to the body. Along with this comes the fact that PFCs accumulate in the body over time, leading to undesired side effects.


To conclude, although we do not have a substitute for blood yet, we have been making considerable progress. As scientists learn more about how natural RBCs function in the body, they will come closer to inventing a blood substitute for humans that has few side effects, an increased oxygen-carrying capacity, and a longer-lasting survival time in the human body. Despite our challenges, we're steadily advancing towards a breakthrough that could transform healthcare. The idea of replicating blood might seem daunting, but it symbolizes our unyielding spirit to overcome obstacles. This quest isn't just about solving problems; it's a testament to our determination to create a brighter medical future.



Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2738310/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086064/

https://stanfordbloodcenter.org/pulse-artificial-blood-the-future-of-patient-care/

https://www.youtube.com/watch?v=sZ5wMZE9_QQ

https://www.youtube.com/watch?v=JnUq2V5W9PA

https://www.scientificamerican.com/article/how-do-scientists-make-ar/


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