A potential game-changer for emergency medicine: synthetic platelets

Imagine you are a paramedic treating a trauma patient who is bleeding severely. You know your patient’s life is in danger, but there is not much you can do because the patient needs an IV with blood containing platelets. Platelets promote clotting, help stop bleeding and are critical in emergency situations like these. But there is none on board your ambulance.

It turns out it’s not an uncommon problem.

Unlike whole blood (plasma, red and white blood cells and platelets) which can be stored under constant refrigeration for up to a month, platelets themselves require a different and even more challenging form of attention. They require constant stirring to prevent clumping, and they must be kept at room temperature to maintain their clotting function. Due to the increased risk of bacterial contamination at room temperature, they have a shorter shelf life.

“Platelets only last about five days,” says Ashley Brown, Ph.D., associate professor in the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill. “This makes them one of the weakest yet most critical links in the chain when you look at blood products that we need to have quick access to.”

And that’s just the beginning of the trouble. Platelets are often in short supply because they come from human donors, they are difficult to transport and they can pose contamination risks.

A miracle solution?

To overcome these obstacles, Brown and her team have come up with something new that might just tick all the boxes: synthetic platelets. The synthetic platelets they designed have a long shelf life, can be stored under a variety of conditions and pose no contamination risks in the animal models on which they have been tested so far.

The platelets are made using hydrogel nanoparticles: gels that are invisible to the naked eye and are formed by a mixture of water and a small amount of polymer molecules to give them structure. Brown calls the magical result “Jell-O on a microscale” – except for one improvement.

“We designed the platelets to be extra soft,” Brown said. “It was very important for us to mimic the characteristics of natural platelets.”

One area where these synthetic platelets really excel is their ability to focus on the site of injury after being injected intravenously, says Ronald Warren, Ph.D., program director in the Division of Blood Diseases and Resources at NHLBI. “Other methods of treating internal bleeding may carry the risk of off-target clots forming, which could lead to a stroke, heart attack or pulmonary embolism,” he explained.

Brown’s platelets are designed to pick up antibody fragments on the surface of the hydrogel that bind to a protein called fibrin, which is naturally produced when the body is injured. The platelets use the antibody as a homing mechanism to move directly to the site of injury. The job of the fibrin is to generate a mesh-like substance that promotes clot formation. The researchers found that the synthetic platelets can help stiffen and stabilize the clot, which then promotes the wound healing process after clotting has occurred.

“This was a very exciting find and a total surprise when we first discovered it,” Brown said. She explained that when someone bleeds excessively, the body is unable to produce enough fibrin. But if she is given platelets, they can actually accelerate fibrin formation.

After reaching the site of injury and becoming active, the platelets, due to their softness, can also change shape: from round to more star-shaped, mimicking what natural platelets do in the body. This change stimulates a process called clot retraction, or the shrinking of a blood clot, so that the edges of the damaged blood vessel wall can slowly be brought back together for repair.

The softness of the platelets gives them another advantage at the end of the process. “They can penetrate through pores much smaller than their size, allowing them to be excreted by the kidneys,” Brown said. “Normally they would accumulate in the liver, which could have harmful consequences.”

Still testing – and promising

Brown and her research team have tested the synthetic platelets in several animal models and so far the results have been positive. In mice with liver damage, the synthetic platelets went directly to the site of the injury and had the lowest blood loss compared to mice given normal platelets or a saline control solution. Seven days after the injury, mice given synthetic platelets also had the smallest wounds, a sign of improved healing. When tested in rats with an injury to the blood vessel instead of the liver, the researchers found similarly promising results.

But Brown said pigs are the gold standard because of their ability to provide further insight into how synthetic platelets may work in humans. When administered immediately after liver injury in pigs, the synthetic platelets traveled to the site of injury and reduced blood loss. They also caused no measurable allergic or immune system reactions and were excreted by the kidneys within two hours of injection.

“We think synthetic platelets could be the best thing since sliced ​​bread, but that remains to be determined through further testing,” Brown said. Her team is still experimenting to find the ideal conditions to store the platelets for the best results. Currently, tests show that they can be stored as a freeze-dried powder, which could be useful in ambulances or similar trauma situations such as the battlefield, or suspended in a solution that may be better for hospital use.

While they continue to test storage conditions, Brown has formed a company with her colleague Seema Nandi, Ph.D. serve as CEO. SelSym Biotech focuses on completing all necessary steps, such as manufacturing, preclinical studies and clinical trials, to use synthetic platelets clinically. It will evaluate the long-term stability and safety of the platelets, and work out the processes for scaling up production after human testing shows they are safe and effective. Brown expects these processes to begin in about two years.

“By developing a new generation of treatment options for emergency medicine, this research can help improve patient outcomes while reducing healthcare costs,” said Warren. “Unlike donated platelets, which can vary in quality, synthetic platelets can potentially be produced in large quantities with uniform quality and performance.”

Brown said she is hopeful that the platelets will soon find their way into emergency medical services, military medic kits and hospitals, so that her “highly motivating” work to save lives finally pays off.

“So many people are dying from unnecessary bleeding,” she said. “I am hopeful that this work can have a major impact.”