Synthetic microparticles accelerate thrombosis
American researchers from Georgia Tech University, Emory University and Arizona State University have developed a new class of synthetic thrombocyte-like particles capable of accelerating the formation of blood clots in traumatic injuries and other situations requiring urgent bleeding arrest.
Blood contains a whole complex of compounds known as the coagulation system. This complex includes proteins that are precursors of fibrin, a protein polymer that forms the basis of blood clots. Upon receiving the appropriate signals from the thrombin protein, these precursors begin to polymerize in the bleeding area.
After activation, circulating platelets are distributed inside the fibrin matrix
and they are undergoing significant structural changes. The figure schematically shows the stages of this process.
Activation of the particles developed by the authors from a soft deformable hydrogel occurs under the action of the same trigger, that is, in parallel with the activation of the natural mechanism of blood clotting. This was achieved through a process known as molecular evolution, as a result of which antibodies were synthesized that attach to hydrogel particles and change their shape when interacting with fibrin activated by the action of thrombin. These antibodies have a high affinity for the polymerized form of fibrin and a low affinity for its precursors.
The structure of a thrombocyte-like particle: a uniquely deformable hydrogel (green)
and antibodies binding to fibrin protofibrils (blue).
The effectiveness of thrombocyte-like particles was successfully tested on an animal model of traumatic injury, as well as in a microfluidic chamber reproducing blood flow conditions in the body.
In addition to the ability to reproach the process of thrombosis, microparticles, whose physical properties differ in many ways from those of platelets, unexpectedly demonstrated that, like natural thrombi, the thrombi formed with their participation shrink in size over time, although at a slower rate.
The most significant results were obtained in a series of experiments in a microfluidic chamber, the inner surface of the microchannels of which were covered with human vascular endothelial cells. As a liquid medium, the microchannels were filled with whole blood from adult donors, as well as blood that did not contain platelets and, accordingly, was not capable of forming blood clots. The addition of thrombocyte-like particles ensured the formation of blood clots in both versions of the experiment.
The researchers also conducted similar experiments with the blood of infants undergoing open-heart surgery. In such cases, in order to avoid the formation of blood clots during and after surgery, the patients' blood is pre-diluted. The addition of platelet-like particles to such diluted blood also restored its ability to coagulate.
At the last stage of the study, the authors analyzed the behavior of thrombocyte-like particles in the blood of patients with hemophilia that did not contain coagulation factors necessary to start the fibrin polymerization process. As expected, in this case, the introduction of microparticles did not have the desired effect.
Initially, thrombocyte-like particles, whose diameter does not exceed 1 micron, were developed for self-administration by wounded soldiers directly on the battlefield using a smartphone-sized device. However, the authors believe that they can reduce the need of clinics for expensive and limited shelf life of donor platelet mass for transfusion to patients undergoing chemotherapy or coronary artery bypass grafting, as well as those suffering from a number of diseases of the blood system.
In the near future, researchers plan to investigate the fate of hydrogel platelet-like particles in the body. They note that, as a rule, particles of this size and composition are easily removed from it.
Before the introduction of this promising development into clinical practice, it must undergo clinical trials and receive approval from the US Food and Drug Administration.
Article by Ashley Brown et al. Ultrasoft microgels displaying emergent platelet-like behaviours is published in the journal Nature Materials.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Georgia Institute of Technology:
Platelet-like particles augment natural blood clotting for treating trauma.
10.09.2014