A new way to halt internal bleeding, the technology, which mimics the body’s closing process, can help keep injured people alive until they can be treated in a hospital.
MIT engineers have developed a two-part system that can be injected into the body and help clot blood at the site of internal damage. These substances, which mimic the way the body creates clots, may provide a way to keep people with serious injuries alive until they have to go to the hospital.
In a mouse model of internal injuries, the researchers showed that these materials – nanoparticle and polymer – were more effective than hemostatic nanoparticles that had been developed before.
“What is particularly remarkable about these results is the level of recovery from severe injuries that we have seen in animal studies. By introducing two support systems in a row, it is possible to get stronger contractions,” Paula Hammond, a professor at the MIT Institute, head of the department of chemical engineering at MIT, a member of the Koch Institute for Integrative Cancer Research and the group said. of the leaders of the subject and study.
Unlike previously developed hemostatic systems, the new MIT technology mimics the behavior of platelets – the cells that cause blood clots – and fibrinogen, a protein that helps form clots.
“The concept of using two components allows to choose the gelation of the hemostatic process as the tissue increases in the wound, mimicking the end of natural coagulation,” says Bradley Olsen, Alexander and I. Michael Kasser, professor of chemical engineering at MIT and lead author of the study.
Celestine Hong PhD ’22, a postdoctoral fellow at MIT, is lead author of the paper, which appears in Advanced Healthcare Materials. Other authors of the paper include postdoctoral fellow Yanpu He, undergraduate student Porter Bowen, and Professor Angela Belcher, head of MIT’s Department of Biological Engineering.
Artificial clotting
Blood loss from accidents such as car accidents causes more than 2.5 million deaths each year worldwide. The wrong kind of injury can cause internal bleeding from organs like the liver, which is difficult to diagnose and treat. In such a situation, it is 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 could have a big impact in the military, where delayed treatment of internal bleeding is a major cause of preventable death, Olsen said.
When internal damage occurs, platelets are attracted to the site and stimulate blood clotting, which eventually forms a platelet plug and clumping proteins, including fibrinogen. However, if patients lose a lot of blood, they don’t have enough platelets or fibrinogen to form a clot. The MIT team wanted to develop an artificial system that could help save lives by replacing these two parts of coagulation.
“What researchers in this field have done in the past is try to find out the therapeutic effect of platelets or find out the role of fibrinogen,” Hong says. “What we’re trying to do in this project is to capture how they interact.”
To achieve this, the researchers developed a system with two types of material: a nanoparticle that recruits platelets and a polymer that mimics fibrinogen.
For the platelet recruitment particles, the researchers used particles similar to the ones 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. allowing them to bind to activated platelets. Since platelets are attracted to the site of injury, these factors also accumulate at the site of injury.
In this 2022 study, researchers found that when these targeted particles were in the size range of 140 to 220 nanometers, they accumulated at the wound site but did not accumulate significantly in the wound. will be dangerous to the patient.
For this paper, the researchers changed these factors by adding a chemical that would react with the tags placed in the second part of the process, which they called a cross linker. These binders, made of PEG or PEG-PLGA, bind to the target material that has accumulated at the wound site and forms clumps that mimic blood clots.
“The idea is that these two things circulate in the blood, if there is a wound, the target organ will start to gather at the wound site and bind to the target. Cross-linking, ” said Hong. “When those two things are in high concentration, you get more cross-links, they start to form this glue and help with the process.”
Stop the bleeding
To test the system, researchers use a mouse model of internal injuries. They found that after being injected into the body, the two-component system was very effective at stopping bleeding and worked about twice as well as the target alone.
Another important advantage of clots is that they don’t break as easily as natural clots. When patients lose a lot of blood, they are often given intravenous saline to maintain their blood flow, but the saline solution also dissolves existing platelets and fibrinogen, causing clots. becomes stronger and collapses faster. However, the producers are not as sensitive as this type of damage, the researchers found.
The researchers also found that their nanoparticles did not induce any immune response in the mice compared to glycemic control. They now plan to test the method 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 take a closer look at the nanoparticles injected when they enter the body. This can help doctors or emergency medical responders quickly identify the source of internal bleeding, which can now be done in hospitals with MRI, ultrasounds or surgery.
“It can take hours to find the source of the bleeding, and it takes several steps to treat the bleeding. So being able to integrate this process with a research tool is an area that interests us,” said Hong.
Source: MIT
