April 30, 2024

At a Glance

  • Synthetic blood platelets stopped bleeding and sped wound healing in animals with internal injuries.
  • The synthetic platelets didn’t accumulate in other organs and were rapidly excreted, indicating that they’re likely safe for testing in people.

Uncontrolled bleeding after trauma—whether from an accident, injury, or during surgery—can prove fatal. Transfusions of donated platelets, the tiny blood cells that promote clotting, are often used to help stop emergency bleeding. But platelets don’t last long outside the body, are difficult to store, and are sometimes contaminated with bacteria. Consequently, they’re often in short supply or unavailable in emergency settings like an ambulance.

Engineered compounds that promote clotting have been developed to replace platelet transfusions. But these compounds have drawbacks, including high costs. And biocompatible glues can be used on the skin, but not for internal bleeding. To overcome these shortfalls, researchers have been working to develop synthetic platelet-like particles, or PLPs.

A research team led by Dr. Ashley Brown from North Carolina State University has developed one such PLP. It consists of an ultrasoft microgel particle linked to a piece of an antibody that binds to fibrin. Fibrin is a protein found in wounds that helps blood clot. Targeting fibrin allows the PLPs to home in on wounds. The ultrasoft nature of the particles lets the PLPs change shape and compress their size. Such traits might let them mimic the behavior of real platelets and speed the healing process.

In previous studies, the researchers showed that clots formed by their PLPs mimicked properties of clots formed by natural platelets. In a new study, funded in part by NIH, they optimized PLP binding to fibrin and tested several versions of their synthetic platelets in mice, rats, and pigs with internal injuries. Results were published on April 10, 2024, in Science Translational Medicine.

In mice with traumatic liver injury, the PLPs collected at the injury sites. In contrast, the top synthetic platelet candidate wasn’t found in substantial numbers in other organs such as the heart, lung, and kidneys. Compared to mice given normal platelets or a control solution of saline, mice with liver injury given the PLPs had the lowest levels of blood loss. At seven days after injury, mice given the PLPs also had the smallest wounds, a sign of improved healing.

A similar reduction in blood loss was seen in rats given the PLPs after injury to a blood vessel. In additional studies in mice, the team found that the PLPs rapidly cleared from the body through urine in the absence of an active injury.

Finally, the researchers tested their top PLP candidate in pigs, an animal model closer to people. When given immediately after a liver injury, the PLPs traveled to the site of injury and reduced blood loss. They didn’t cause any measurable allergic or immune system reactions, and began to be excreted by the kidneys as soon as two hours after injection.

“In the mouse and pig models, healing rates were comparable in animals that received platelet transfusions and synthetic platelet transfusions,” Brown says. “And both groups fared better than animals that did not receive either transfusion.”

While the PLPs bound to fibrin at the wound sites, the current versions don’t have all the functions of natural platelets. The team plans to develop next-generation synthetic platelets with additional features like the ability to clump together and to send signals to immune cells. They also hope to begin human studies within the next several years.

—by Sharon Reynolds

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References: Ultrasoft platelet-like particles stop bleeding in rodent and porcine models of trauma. Nellenbach K, Mihalko E, Nandi S, Koch DW, Shetty J, Moretti L, Sollinger J, Moiseiwitsch N, Sheridan A, Pandit S, Hoffman M, Schnabel LV, Lyon LA, Barker TH, Brown AC. Sci Transl Med. 2024 Apr 10;16(742):eadi4490. doi: 10.1126/scitranslmed.adi4490. Epub 2024 Apr 10. PMID: 38598613.

Funding: NIH’s National Heart, Lung, and Blood Institute (NHLBI), National Institute of General Medical Sciences (NIGMS), and Office of the Director (OD); U.S. Department of Defense; North Carolina Biotechnology Translational Research Grant; North Carolina State University Research and Innovation Seed Funding; National Science Foundation; North Carolina State University Chancellor’s Innovation Fund; U.S. Department of Veterans Affairs; American Heart Association.