Assistant professor of surgery & bioengineering at the University of Pittsburgh, Susan Shea talks about synthetic blood being made available.
Interview conducted by Ivanhoe Broadcast News in 2023.
The blood you’ve seen firsthand blood shortages impacting patients, tell us about that.
Shea: Yes. Blood in general is a burdensome biologic to maintain in an inventory at a hospital. Any blood product has a limiting shelf-life and has to be stored cold. In addition, that’s coupled with a donor shortage that has been made worse by the COVID-19 pandemic. That shortage and the required storage has limited the availability of blood in hospital for both adult and pediatric patients. Especially trauma patients and surgical patients are not getting the blood that they need due to this shortage.
What’s the motivating factor for creating synthetic artificial powdered blood?
Shea: Due to the difficulties of maintaining the blood supply in a hospital, especially for trauma patients. Of course, in the military setting, getting blood to war fighters that need resuscitation, this burden of storage, cold storage, and limited shelf life really impacts the availability of these products. The holy grail for transfusion is a dried artificial whole blood. This is an absolute game changer. Not only does it eliminate the requirements to type match blood because it is synthetic, but it also is shelf stable, allowing it to be transported and stored much longer than current products, orders of magnitude longer. That will really allow us to get treatments to patients as soon as possible at the time of injury.
Talk to me a little bit about what you just said, blood type isn’t that important with this. How do you explain that? How is that possible?
Shea: We’re using synthetic components for the cellular aspects of blood, those type mismatches will not occur because what transfusion recipients are reacting to are markers on the surfaces of red blood cells and other markers in the blood that when we make those things synthetic no longer becomes a compatibility issue.
If someone is A positive, what would they need to look for in A positive liquid blood versus what are you talking about?
Shea: If you’re A positive, your cells are expressing vector A and that you’re positive. When you receive a transfusion, anything that is not self, so anything that’s B is going to be reacted to. Because you’re positive you don’t have to worry about reacting to the positive part, but people who are negative have to worry about reacting to donors who have positive blood types. You might make antibodies that are anti B. If you receive a transfusion that is type mismatched, you would have a reaction to something that is not your type. Universal blood donors don’t express those surface markers that designate them as A or B and whole blood and in red blood cells, and that allows them to be donated to any patient.
With the synthetic blood, you don’t need to look on the shelf and buy the A positive?
Shea: Exactly. The synthetic blood eliminates the need for type matching because those- the cellular components are artificial and they therefore will not express those markers that recipients might have an adverse reaction to as they would if they receive a type mismatched blood donation.
You had mentioned military fighters maybe in the field, is the volume significant enough that rather than carrying a backpack full of liquid blood you can carry X amount more of artificial supply of blood?
Shea: I think the shelf-life advantages and the lack of needing to put this in the cold are what really make it advantageous for transport far forward. You could have a dried blood packet in the medics bag that when needed is mixed with liquid. I think in the final formulation, this will all be put in a product together with whatever liquid, if that’s just water and kind of like a break and shake format. We’re a bit far away from that final product design but that’s exactly the intent. This will be easier to carry. You still will need some liquid to rehydrate the product, but it will not need to be transported in any special way.
A pint of blood is equal to X amount of artificial blood?
Shea: I don’t know that we necessarily know the one to one. What we’re doing at the University of Pittsburgh is focusing on the hemostatic efficacy of the artificial blood products. We’re trying to finalize the co-administration of the components of the synthetic blood, as well as understand what it does in resuscitation. How does it restore the blood clotting function? All of those factors will go into a dose formulation at the end of our study and when this product moves forward. Both efficacy from the clotting perspective, from the oxygen delivery perspective, and then the volume perspective is important as well. All of those things will be taken into consideration. I think it’s unlikely that less volume overall would need to be transfused to a patient because that volume resuscitation is a part of the overall resuscitative process, if that makes sense..
What is synthetic blood?
Shea: This product that we’re developing will consist of a nanoparticle that is able to perform the function of a red blood cell so it can deliver oxygen. Then we also have a nanoparticle platelet that mimics platelet function and can augment the function of existing platelets. Those are the two synthetic components of our product. This will be formulated with human plasma, that is dried. Also both nanoparticle constructs will be dried and the plasma product will also be dried and put together to make synthetic blood.
There are other things with the human plasma that you can’t just walk in and donate blood. Is it the same true with the plasma?
Shea: Yes. The plasma will be manufactured as it currently is in blood banks, but further processed to be lyophilized, meaning dried, able to be reconstituted with water. That process makes it safer and eliminates a lot of these needs for type matching.
The team can make a much more long lasting and mobile liquid blood it needs today, is there anything you want to say about that?
Shea: The ability of this product to be transported, administered immediately at the point of injury is absolutely transformative, especially in the field of trauma care. But for any patient that needs a blood product or a transfusion or hemostatic resuscitation, the longer that these patients wait to receive treatment, the more likely they are to die. This absolutely will save lives both in the civilian setting and abroad, in the military if we can get this blood into injured patients immediately.
What are the statistics of shelf life?
Susan Shea: It’s 35 days and the target transfusion day is 26. The current whole blood unit that we’re comparing with is stored for 35 days in the cold. This product, this artificial whole blood, is dried and therefore its shelf life could be anywhere from one to two years or beyond, and the ability to store it at room temperature and have it be shelf stable is a game changer for supply, demand, stockpiling, and transport.
Does liquid blood have to be frozen?
Shea: It doesn’t have to be frozen, it has to be stored in the cold, the fridge.
And it’s how much longer?
Shea: Thirty five days is our comparative products. Depending on how blood is manufactured, it has a different shelf life. There’s different ways to make a whole blood product. The blood that is in use by the military has a 35-day shelf-life, that’s our target. Blood in theater is most often transfused at 26 days. Our goal is to make a product that is no worse than a 26 day whole blood transfusion.
What is the research right now? When do you think synthetic blood would become prominent everywhere?
Shea: I hope sooner, as soon as possible. I think that it would save lots of lives. Right now we are just kicking off this effort at the University of Pittsburgh. We will be performing hemostatic testing. We’re testing the ability of this product to clot and we’re collaborating with the other institutions involved in the project to optimize the manufacturing and co-administration of this product in the very early stages. We hope that this will be in human testing in six to eight years. Hopefully that’s our timeline for getting it into humans and soon after that and to patients. But since this will be such a transformative product right now, anything that we can do to accelerate this process is highly desirable.
Do you think you’ll ever replace traditional liquid blood, donating blood, do you think that will ever replace or will always there be need for that?
Shea: I don’t think that traditional donation will ever be replaced, but I think what this product can do is ensure that all patients get the transfusions that they need. Right now, there’s a blood shortage that’s preventing patients from getting blood from our current supply, so anything that we can do to help alleviate that and spread the resources around is advantageous and will save lives.
Are there any downsides to this synthetic blood? Is there anything that’s like you can’t use synthetic blood?
Shea: I think transfusions are given to different patients for various needs. This product is certainly ideal for the trauma patient, especially with the optimization for immediate administration. But I think one thing that this product will allow us to do is personalize how we package the product, and we could make different synthetic blood formulations for different patient populations catering to their specific needs. At this point, we’re focusing on trauma, but we can certainly titrate the dosing and the relative co-formulation once we’re at that point to cater it to what different patients need.
Is is there any way at this point, you see where all these patient are actually going to be able to use it?
Shea: No, I think on the contrary, this product will allow us to transfuse more patients because of the synthetic components. For those that don’t want to receive a biologic product, the direction that we’re going here is that we will have an alternative option that does not have a biologic component and can still provide that hemostatic resuscitation and treat the patient.
Do you see this as being safe with them?
Shea: I think there’s a good chance that this product has safety advantages over current blood products. Due to the risk of disease transmitted through the blood supply is still present, and our blood supply is safe and there’s lots and lots of testing that goes into manufacturing current blood products. By making a synthetic dried product, we are also eliminating the risk of disease transmission through transfusion.
In regards to the downsides in this synthetic there was fall if this happens, do you foresee the time when there would never be a blood shortage?
Shea: I think we would all dream and hope that there would be a time that there would never be a blood shortage. I sincerely wish that we get to that point. I don’t know that we can guarantee that this product alone will eliminate the blood shortage, but it’s certainly a very important step forward.
What is blood, what functions does it have? What functions do you need the synthetic blood to perform as well? And that touches on coding and oxygen you talked about, what is blood? What function does it perform? What do you need synthetic blood? What functions do you need synthetic blood to?
Shea: Whole blood transfusion is a critical aspect of treating trauma patients and other patients that are bleeding because blood specifically supplies both volume resuscitation. Volume resuscitation is important to ensure that our cardiovascular system is pumping adequately, and supplies oxygenation capabilities. Of course, one very important function of blood is to deliver oxygen to our organs and tissues. Then the other aspect is that it supplies hemostatic capability, meaning blood needs to clot. Not only does it need to clot when somebody is injured or when a vessel is injured, but it also works to maintain all of our blood vessels. When blood volume is lost, our blood vessels experience shock. By reducing the volume of blood in our bodies, our cells start sending out danger signals. These things all work together to not only keep us alive when we’re healthy, but when we are injured and we receive a transfusion. The combination of volume resuscitation, oxygenation, and hemostasis are all intertwined. When somebody is critically injured and loses large volumes of blood, they all are interconnected and leading to dysfunction in our clotting system in the patient, resulting in both difficulty in resuscitating the patient, but also difficulty in treating this patient if they survive long term. The sooner that we can get that volume oxygenation and clotting ability restored, not only do we increase the chances of getting a trauma patient to the hospital for further treatment, but we actually increase their chances of long-term survival. Once we get them there and now they are less sick, and so they are easier to treat.
The characteristics of this, is it essentially when you get the blood? Is it essentially the same blood?
Shea: Interestingly, blood thinners, that’s a misnomer because they actually don’t change viscosity or anything. I always thought that before I learned what they actually do, but they’re anticoagulants. One thing about this product is that the primary goal is really acute resuscitation. In the moment that a patient is critically bleeding, we really need to restore that blood volume, that oxygenation capability and hemostasis as fast as possible to get them to a hospital where we can treat them. The design of this product being geared towards that acute, very quick volume restoration and function restoration. We can switch to different therapies once the patient is in the hospital and go back to more standard and established. I don’t want to say standard established, but once we get them to the hospital, we can resume and continue with all treatments that they were receiving previously. There really should be no major impact of this product specifically on the other underlying conditions of the patient. Of course, the traumatic injury and the bleeding is a major hit. But this product, if anything, will just allow that person to continue to get any treatment that they were receiving before the time of injury.
That it’s not necessarily a super blood but it’s a match functional blood?
Shea: Yes. Currently the goal is to replicate the function of current transfused blood. What this will allow us to do in the future is cater the formulation of this product to perhaps enhance the efficacy of the product when it’s transfused as well as catering it to specific patient populations that need different things. While not a super blood, it will certainly allow us to give more effective transfusions in the future.
Can you define UPMC a bit and your involvement, our involvement and why here?
Shea: UPMC in the University of Pittsburgh really is just a perfect place for this work to happen. We have a longstanding history of being leaders, especially in the trauma research field and of course, many other fields relevant to this work. Of course, the additional existing strong connections between bioengineering and UPMC and our multidisciplinary collaborative team that we’ve established here, make us the perfect group to assess the function of this product and help with its development.
Why can this be used in those rural settings? First of all, is it a problem for rural police access to what? Then how this would need a dress that niche fill that gap for access for people?
Shea: Due to the current limitations on blood products shelf life, and the need for cold storage, which can really be a burden on some centers, many hospitals and especially rural hospitals do not have a blood supply or do not have a substantial blood supply to support treatment of trauma patients or surgical patients or every patient that might need blood if they have it at all. The fact that this product will be shelf-stable, be able to be stored at room temperature, does not require being put in the fridge or the freezer, that will allow lots of centers to stock this product because it reduces that need to discard a product at the end of the shelf-life that you paid for without transfusing it. These centers will be able to stop this product, use this product, and that will really allow us to get to increase the reach of the blood supply and help places that currently can’t afford to maintain a current blood products storage system, get a hemostatic resuscitation transfusion capability with this synthetic blood products.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Anastasia Gorelova
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here
