Synthetic platelets stop bleeding quickly

In the United States, trauma-related uncontrolled bleeding remains one of the highest causes of mortality annually (1). Better bleeding management protocols could help to prevent many of these cases. However, emergency care providers often lack enough ways to control bleeding.

Ashley Brown wears a black suit jacket and pink shirt

Ashley Brown and her team study the pathways involving blood coagulation and develop new technologies for life-saving interventions.

CREDIT: University of North Carolina Blood Research Center

Biomedical engineer Ashley Brown and her team of researchers at North Carolina State University and the University of North Carolina at Chapel Hill engineered synthetic platelet-like particles (PLPs) that helped control blood loss in animal models of traumatic injury (2). This potential new therapy could one day aid in acute emergency situations.

“Platelets are really important because they're the primary cell type that’s involved in helping with forming a clot,” said Brown. Unlike donor red blood cells, which can remain in storage for a little over a month, platelets only have a shelf life of about seven days and must be kept at room temperature to maintain their function.

“This creates a pretty big supply issue because even if you're able to bank a ton of platelets, they very quickly go bad,” Brown added, “What we were interested in doing was creating a synthetic platelet alternative that essentially could be mass produced, could be stored for long periods of time, and could be easily deployed in emergency medicine.”

The researchers made their PLPs in two parts: a soft, microgel backbone and an antibody fragment that sticks to fibrin, the main protein in clots. The gel can change size depending on the temperature. At body temperature, it becomes bigger and softer, like a natural platelet.

“Basically, it's a squishy particle that's about a micron in diameter. That's about the same size as platelets before they become activated,” Brown said. “So, these squishy particles mimic the size and basically mechanics and morphology of normal platelets.”

The fibrin antibody directs the PLPs directly to the injury site. “It binds to the fibrin at the site. It helps to stabilize any fibrin that is forming, and then it catalyzes that [process],” she said.

Brown and her team then tested if the PLPs could stop bleeding in mouse and pig models. They performed a liver laceration surgery on the animals while administering PLPs to them intravenously. Using fluorescence imaging, the researchers found that the PLPs accumulated at the wound site. To assess blood loss, the researchers measured the volume of blood collected on a surgical sponge placed under the injury site at various time points after the procedure. Both mice and pigs treated with PLPs displayed significantly less blood loss than control groups receiving normal platelets or a saline solution. Importantly, no measurable allergic or immune reactions were observed upon PLP administration.

What we were interested in doing was creating a synthetic platelet alternative that essentially could be mass produced, could be stored for long periods of time, and could be easily deployed in emergency medicine.
- Ashley Brown, North Carolina State University and the University of North Carolina at Chapel Hill

Histological analysis of liver tissue sections seven days after injury revealed smaller wound areas in mice treated with PLP, indicating improved healing and tissue repair.

Through atomic force microscopy measurements on urine and blood samples collected after PLP injection at different time points, the researchers saw that the body rapidly eliminated the PLPs through renal excretion. This suggested a favorable safety profile with a low risk of unintended side effects and organ accumulation.

“The technology is really unique and elegant,” said Sarah Stabenfeldt, a biomolecular engineer at Arizona State University who was not a part of this study. “Brown and her collaborators have really demonstrated … how these materials respond even dynamically and undergo collapse when they engage in clots.” She added, “It's highly impactful for not only the material science world but also the potential for clinical translation.”

Brown and her team are eager to continue evaluating their PLPs in combination with other therapies, including natural platelets, as well as testing how repeated dosing compares to a single dose of PLPs.

“Blood products are currently not carried in emergency medicine situations,” Brown said. “But this is something that can be. It takes up small volumes. It could very easily be transported. It has a really long shelf life. So, in terms of giving first line care in an emergency medicine situation, you can at least stabilize the patient to get to the hospital. … I could see a major impact for this product.”