Developed by engineers at the Massachusetts Institute of Technology (MIT), the two-component system can be injected into the body and help form blood clots at the sites of internal injury.
The materials, which mimic the way that the body naturally forms clots, could offer a way to keep people with severe internal injuries alive until they can reach a hospital, the researchers said.
In a mouse model of internal injury, the team showed that the components performed significantly better than haemostatic nanoparticles that were previously developed.
“What was especially remarkable about these results was the level of recovery from severe injury we saw in the animal studies. By introducing two complementary systems in sequence it is possible to get a much stronger clot,” said Professor Paula Hammond, one of the senior authors of a paper on the study.
Unlike previously developed haemostatic systems, the new MIT technology mimics the actions of both platelets, the cells that initiate blood clotting, and fibrinogen, a protein that helps form clots.
“The idea of using two components allows selective gelation of the haemostatic system as the concentration is enhanced in the wound,” said Professor Bradley Olsen, a senior author of the study.
If patients are losing a lot of blood, they do not have enough platelets or fibrinogen to form clots. The MIT team wanted to create an artificial system that could help save people’s lives by replacing both of those clotting components.
“What researchers in this area have been doing in the past is trying to either recapture the therapeutic effects of platelets or recapture the function of fibrinogen,” said lead author Celestine Hong. “What we are trying to do in this project is to capture the way they interact with each other.”
For the platelet-recruiting particles, the researchers used particles similar to those they reported in a 2022 study, made of a biocompatible polymer called PEG-PLGA.
The team modified those particles by adding a chemical group that would react with a ‘tag’ placed on the second component in the system, which they called the crosslinker. Those crosslinkers, made of either PEG or PEG-PLGA, bind to the targeting particles that have accumulated at a wound site and form clumps that mimic blood clots.
“The idea is that with both of these components circulating inside the bloodstream, if there is a wound site, the targeting component will start accumulating at the wound site and also bind the crosslinker,” said Hong. “When both components are at high concentration, you get more cross-linking, and they begin forming that glue and helping the clotting process.”
To test the system, the researchers used a mouse model of internal injury. They found that after being injected into the body, the two-component system was highly effective at stopping bleeding, and it worked about twice as well as the targeting particle on its own.
The researchers also found that their nanoparticles did not induce any significant immune reaction in the mice compared to a glucose control. They now plan to test the system in a larger animal, working with researchers at Massachusetts General Hospital.
In the longer term, the researchers hope to explore the possibility of using portable imaging devices to visualise the injected nanoparticles after they have entered the body. This could help doctors or emergency medical responders quickly determine the site of internal bleeding, which can currently only be done at a hospital with MRI, ultrasound, or surgery.
“There can be hours of delay in figuring out where the source of the bleeding is, and that requires a lot of steps before the bleeding site can be treated. So being able to combine this system with diagnostic tools is one area that we're interested in,” said Hong.
The work was funded by the US Army Research Office and the Department of Defence. The paper was published in Advanced Healthcare Materials.
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