Microgel Particles Boost Blood Clotting

Colorized scanning electron micrograph of blood cells entangled in the fibrin mesh of a clot.David Gregory and Debbie Marshall, all rights reserved by Wellcome Images.

When you accidently cut yourself, your body initiates a multistep process to stop the bleeding in minutes. Platelets, which circulate in blood in an inactive form, become stimulated when they encounter the damaged area. They adhere to the wounded part of the blood vessel and release chemicals to attract more platelets to the region.

Another crucial player is fibrinogen, which also circulates in your blood and is converted to fibrin during blood clotting by the enzyme thrombin. Strands of fibrin stick together inside the wounded vessel. The platelets bind and spread within the fibrin mesh. They deform and trigger the fibrin matrix to contract. This forms a plug, which slows or stops the bleeding. As the tissue damage heals, the fibrin strands and other components are naturally degraded.

Severe trauma can be fatal if the bleeding isn’t controlled. Thus, scientists are working to develop ways to improve clot formation and wound management. A team led by Drs. Andrew Lyon and Thomas H. Barker of the Georgia Institute of Technology set out to create platelet-like structures that could increase clotting. The research was funded in part by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Heart, Lung, and Blood Institute (NHLBI). Results appeared online on September 7, 2014, in Nature Materials.

The researchers created “platelet-like particles” by synthesizing deformable microgel particles that were 1 micron in diameter, similar to the size of platelets. They then attached human antibody fragments (“nanobodies”) that recognized and bound specifically to fibrin.

The team used a chamber that mimics flow conditions in a blood vessel to test the platelet-like particles. Normal human plasma that was rich in platelets formed clots when triggered by thrombin, as expected. Plasma that was low in platelets didn’t form clots, but when supplemented with platelet-like particles, clot-forming ability was restored. The particles didn’t improve clotting in plasma from patients with a defect in fibrin formation.

The researchers found that the clots formed by the platelet-like particles collapsed over time. While the collapse was slower than that of normal clots, the finding showed that the platelet-like particles could deform and contract, mimicking normal clot behavior.

The platelet-like particles decreased bleeding times and blood loss in a rat model of traumatic vessel injury. Tissue analysis showed that the particles were present at the injury site and enhanced clot formation.

“The specificity of this material provides a very important advantage in triggering clotting at just the right time,” Barker says.

More research will be needed to determine what ultimately happens to hydrogel particles that circulate in the bloodstream. Nevertheless, the design of these particles could serve as model for other therapeutic materials.

—by Carol Torgan, Ph.D.