When donated blood is in low supply, platelets are even scarcer. These cell fragments, which are essential for blood clotting, have a short shelf life. Whereas whole blood can be refrigerated for up to a month, platelets last for just a week at most.
“Even if you have a ton of donations, you can’t bank them for long,” says Ashley Brown, an associate professor in the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill.
To address this problem, Brown and her team have created an artificial substitute that could be stored for long periods of time. In a recent paper in Science Translational Medicine, they describe using their synthetic platelets to stop bleeding and promote healing in rodents and pigs.
Natural platelets circulate in the blood and prevent or stop bleeding by forming clots. Sometimes, the body needs more of them. People with traumatic injuries, cancer, and certain chronic conditions that strip the blood of platelets often require transfusions. Typically, platelets are collected through a process called apheresis, in which a donor’s blood is passed through a tube and into a machine that separates out the platelets. These are funneled into a bag, and the rest of the blood is returned to the donor.
Their limited shelf life also means they’re not often stored in rural hospitals and can’t be easily transported. Brown’s aim is to make an alternative that’s easy to store and ship that could be given to patients sooner, such as in an ambulance or on the battlefield, and regardless of blood type.
To make their synthetic platelets, Brown and her team used a squishy water-based gel called a hydrogel to form nanoparticles that mimic the size, mechanics, and shape of natural platelets. They then designed an antibody fragment that binds to fibrin, a protein that helps platelets form clots, and decorated the surface of the nanoparticles with this fibrin antibody. When an injury occurs, platelets rush to the site of damage to form a temporary plug. Fibrin also gets activated in this process and builds up at the wound site, eventually producing a clot.
To find the optimal dose of artificial platelets needed to stop bleeding, researchers tested a range of doses in mice. They then gave infusions of the artificial version to mice, rats, and pigs and compared them to animals that received natural platelets and those that were not treated with either. All the animals in the study had severe internal bleeding. They found that the synthetic platelets were able to travel through the bloodstream to the wound site to promote clotting and accelerate healing.
Healing rates were similar in animals that received synthetic platelets and those that received natural ones. Overall, both groups fared better than those in the untreated group. Interestingly, the researchers only had to use about a tenth as many artificial particles to get the same healing effects as with natural platelets. “Our mechanism of action is binding to fibrin, so it could just be that our particles are more efficient in that binding,” Brown says. There’s also variability in how labs prepare natural platelets that can affect their quality, which might have accentuated this difference.
Matthew Neal, a trauma and general surgeon at the University of Pittsburgh Medical Center, says replicating the functions of a natural platelet has been a challenge, but after decades of research, the idea of a synthetic substitute is getting closer to reality.
“You have to get the surface decoration of these particles just right. You need to make them look like platelets and make them behave the way platelets do,” he says. “At the same time, we certainly want to avoid any deleterious consequences.” That could include setting off an immune reaction or clotting in parts of the body other than the wound site. Abnormal clotting inside the body can lead to stroke and heart attacks.
In the recent study, the researchers didn’t observe any adverse health effects in the animals that received the synthetic substitute. Brown says the particles that travel to the animals’ wounds most likely end up in scabs that fall off when the wound is healed. Some particles didn’t make it to the wound site but were found in the animals’ urine within about an hour of the synthetic platelets being given. That’s good news, Brown says, because it means that the particles aren’t sticking around in the body.
Another benefit of the artificial platelets is that they’re able to be freeze-dried and then later rehydrated when needed. Unlike plasma and red blood cells, natural platelets are difficult to cryopreserve, as they lose activity when thawed out for use. Natural platelets therefore must be stored at room temperature, and some researchers are trying to find better ways of freezing them.
“Synthetic alternatives that could be frozen or even stored at room temperature in a liquid or freeze-dried form and remain functional when transfused would be a great advance,” says Keith McCrae, a spokesperson for the American Society of Hematology and an oncologist at the Cleveland Clinic Taussig Cancer Institute.
McCrae can imagine several uses for artificial platelets, such as in an ambulance, on the battlefield, or in remote locations far from Red Cross centers, which provide blood products to hospitals and medical centers across the US. Another application might be in cancer patients who develop low platelet counts as a result of chemotherapy. These patients can develop antibodies against transfused natural platelets that eliminate them rapidly, rendering them ineffective, he explains.
The platelets developed by the North Carolina team have yet to be tested in people, but Brown and her colleagues have cofounded a startup called SelSym Biotech to advance their product to clinical trials. Another company, Haima Therapeutics in Cleveland, Ohio, is developing freeze-dried synthetic platelets based on research by Anirban Sen Gupta at Case Western University. Sen Gupta’s team has tested its product in animals but not yet in people.
Human testing is likely just a few years away, McCrae says, and only then will scientists learn whether synthetic platelets are ready for prime time.
