Two-component nanoparticle systems could offer a new way to stop internal bleeding


April 25, 2023

(Nanowerk News) MIT engineers have devised a two-component system that can be injected into the body and helps form a blood clot at the site of an internal injury. These materials, which mimic the way the body naturally forms clots, could offer a way to keep people with severe internal injuries alive until they get to the hospital.

In a mouse model of internal injury, the researchers demonstrated that these components – nanoparticles and polymers – performed much better than previously developed hemostatic nanoparticles.

“What’s so remarkable about these results is the recovery rate from severe injury that we saw in animal studies. By introducing the two complement systems sequentially, it is possible to get much more potent clots,” said Paula Hammond, an MIT Institute Professor, head of the MIT Chemical Engineering Department, member of the Koch Institute for Integrative Cancer Research, and one of the senior authors of the paper on the research. This. synthetic nanoparticles that can be injected into the body and help form blood clots at sites of internal injury MIT engineers have designed synthetic nanoparticles that can be injected into the body and help form blood clots at sites of internal injury. (Image: Christine Daniloff, MIT)

Unlike previously developed hemostatic 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 hemostatic system when concentrations are increased in the wound, mimicking the final effect of the natural clotting cascade,” said Bradley Olsen, the Alexander and I. Michael Kasser Professor of Chemical Engineering at MIT and the study’s senior author (Advanced Health Care Ingredients, “Engineering a Two-Component Hemostat for the Treatment of Internal Bleeding via Wound Targeted Crosslinking”).

MIT postdoc Celestine Hong PhD ’22 is lead author of the paper, which appears in Advanced Healthcare Materials. Other authors of the paper include postdoc Yanpu He, undergraduate student Porter Bowen, and Professor Angela Belcher, who is head of MIT’s Department of Biological Engineering.

Artificial freezing

Blood loss from traumatic events such as car accidents contributes to more than 2.5 million deaths per year worldwide. This kind of blunt trauma can cause internal bleeding from organs such as the liver, which can be difficult to detect and treat. In such cases, it is very important to stop the bleeding as soon as possible, until the patient can be taken to the hospital for further treatment. Finding ways to prevent internal bleeding can have a particularly significant impact in the armed forces, where delayed treatment for internal bleeding is one of the biggest causes of preventable death, Olsen said.

When internal injury occurs, platelets are attracted to the site and initiate the clotting cascade, which eventually forms a sticky plug of platelets and clotting proteins, including fibrinogen. However, if a patient loses a lot of blood, they don’t have enough platelets or fibrinogen to form a clot. The MIT team wanted to create an artificial system that could help save people’s lives by replacing the two components of the freeze.

“What researchers in this field have done in the past is try to recapture the therapeutic effect of platelets or recapture the function of fibrinogen,” said Hong. “What we’re trying to do in this project is capture the way they interact with each other.”

To achieve that, the researchers created a system with two types of materials: nanoparticles that recruit platelets and polymers that mimic fibrinogen.

For platelet recruitment particles, the researchers used particles similar to those they reported in the 2022 study. These particles are made of a biocompatible polymer called PEG-PLGA, which is functionalized with a peptide called GRGDS that allows them to bind to active platelets. As platelets are attracted to the site of injury, these particles also tend to accumulate at the site of injury.

In the 2022 study, the researchers found that when these targeting particles were within the optimal size range of 140 to 220 nanometers, they would accumulate at wound sites but not significantly accumulate in organs such as the lungs, where clot formation would be at risk. to the patient.

For this paper, the researchers modified the particle by adding a chemical group that would react with a tag placed on a second component in the system, which they called a crosslinker. The cross-linkers, which are made of PEG or PEG-PLGA, bind to targeting particles that collect at the wound site and form clots that resemble blood clots.

“The idea is with these two components circulating in the bloodstream, if there is a wound, the targeting component will start to accumulate at the wound site and also bind to the crosslinker,” said Hong. “When the two components are at high concentrations, you get more cross-links, and they start to form that glue and help with the coagulation process.”

Stop the bleeding

To test the system, the researchers used a rat model of internal injury. They found that once injected into the body, this two-component system was highly effective at stopping bleeding, and worked twice as well as the targeting particles themselves.

Another important advantage of these clots is that they do not degrade as quickly as naturally occurring clots. When patients lose a lot of blood, they are usually given intravenous salts to maintain their blood pressure, but these salts also dilute existing platelets and fibrinogen, causing weaker clotting and more rapid degradation. However, the artificial blob is not susceptible to this kind of degradation, the researchers found.

The researchers also found that their nanoparticles did not induce any significant immune reactions in mice compared to glucose controls. They now plan to test the system in larger animal models, in collaboration with researchers at Massachusetts General Hospital.

In the long term, the researchers also hope to explore the possibility of using portable imaging devices to visualize injected nanoparticles after they enter the body. This can help doctors or medical emergency responders quickly pinpoint the location of internal bleeding, which currently can only be done in a hospital with an MRI, ultrasound, or surgery.

“There can be hours of delay in figuring out where the source of the bleeding is, and it takes many steps before the bleeding site can be treated. So, being able to combine this system with diagnostic tools is one of the areas we are interested in,” said Hong.


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