Smart molecules heal wounds.
Text: Angelika Jacobs
When a serious injury occurs, bleeding can overwhelm the body’s healing mechanisms. Artificial molecules could help by giving a boost to the clotting process.
An accident victim is bleeding heavily. Emergency medics need to act fast. The human body is well-equipped to deal with minor injuries thanks to the process of clotting, an ingenious system for closing wounds. However, if the bleeding is too heavy, the body is simply unable to deliver sufficient coagulation factors to the crucial spot, preventing it from forming a clot and stemming the hemorrhage. In emergencies, medical staff can help the process along by administering coagulation factors isolated from donated blood. “However, substances of this sort are expensive to isolate, have a short shelf life and do not work very efficiently,” says Michael Nash.
The Professor of Molecular Engineering and his team are developing smart molecules that can interact with the body’s own clotting mechanism. The goal is to reinforce the resulting clot so as to close the wound more quickly and effectively – not just in the treatment of major injuries, but also for patients with hereditary coagulation disorders or in cases where clotting is hindered by anticoagulant medications.
Platelets and fiber mesh
When a wound bleeds, a change occurs in the blood flow. This mechanical stimulus acts as a signal for platelets to assemble at the site of the injury. The platelets in turn release a messenger substance that prompts the formation of a mesh of fibrin strands. Together, the platelets and the fibrin mesh form the clot that seals the wound.
“This clot has some interesting mechanical properties: the more tension it is subjected to, the more rigid it becomes,” Nash explains. This is in contrast to the everyday observation that an elastic object, such as a tension spring, loses its structure when subjected to excessive strain: if a tension spring is irreversibly damaged in this way, it loses its elasticity and can no longer pull together or extend. Blood clots, on the other hand, actually become more stable the greater the pressure exerted on them by the bloodstream.
Nash and his team hope to further reinforce these particular properties. To this end, they are working with macromolecules consisting of elastic protein chains, known as “elastin-like polypeptides” (ELPs). In a project funded by the European Research Council (ERC), Nash’s team tweaked ELPs so as to allow them to be recognized by the body’s clotting factors at the wound site and incorporated into the fibrin mesh.
Like oil in water
That is not all, however: thanks to an additional trick, the molecules offer a further boost to the clotting process. The ELPs are designed in such a way that their properties change above a certain temperature threshold. At room temperature they are water-soluble, making them easy to store for later use. However, when exposed to the body’s internal temperature of around 37 degrees, they become hydrophobic: like oil in water, which gathers in droplets, the ELPs come together to form nanoparticles, allowing them to circulate in the bloodstream for longer and remain stable. Moreover, this high concentration of ELPs in nanoparticles reinforces their chemical bond with the fibrin strands.