Scientists develop new system to clot blood faster in case of serious internal injuries

How does this two-component system work?

At the time of an injury, platelets rush to the spot and initiate the plugging of the wound. Fibrinogen is a protein that assists the platelets in forming this plug. The two-component system comprises a nanoparticle and a polymer — the former recruits platelets and the latter mimics fibrinogen. If a patient is losing a lot of blood, they don’t have enough fibrinogen or platelets to form clots.

What the team has done is that they have created an artificial system by replacing both these components with a targeting component and a crosslinking component. The idea is that when both these components are injected inside the body, the targeting component accumulates at the wound site and also binds the crosslinker.

Celestine Hong, the co-author of the study, further explains, “When both components are at high concentration, you get more cross-linking, and they begin forming that glue and helping the clotting process.”

The tests were carried out on mice. The team found that the two-component system was extremely effective at stopping bleeding. Another advantage is that the clots formed don’t degrade as fast as naturally occurring clots do.

Paula Hammond, another author of the paper mentioned that the level of recovery from a severe injury seen in animal testing was remarkable. “By introducing two complementary systems in sequence it is possible to get a much stronger clot,” she added in an official statement.

The results have been published in the peer-reviewed journal Advance Healthcare Materials.

Study abstract:

Primary hemostasis (platelet plug formation) and secondary hemostasis (fibrin clot formation) are intertwined processes that occur upon vascular injury. Researchers have sought to target wounds by leveraging cues specific to these processes, such as using peptides that bind activated platelets or fibrin. While these materials have shown success in various injury models, they are commonly designed for the purpose of treating solely primary or secondary hemostasis. In this work, a two-component system consisting of a targeting component (azide/GRGDS PEG-PLGA nanoparticles) and a crosslinking component (multifunctional DBCO) is developed to treat internal bleeding. The system leverages increased injury accumulation to achieve crosslinking above a critical concentration, addressing both primary and secondary hemostasis by amplifying platelet recruitment and mitigating plasminolysis for greater clot stability. Nanoparticle aggregation is measured to validate concentration-dependent crosslinking, while a 1:3 azide/GRGDS ratio is found to increase platelet recruitment, decrease clot degradation in hemodiluted environments, and decrease complement activation. Finally, this approach significantly increases survival relative to the particle-only control in a liver resection model. In light of prior successes with the particle-only system, these results emphasize the potential of this technology in aiding hemostasis and the importance of a holistic approach in engineering new treatments for hemorrhage.