Engineered blood clots form faster to stop severe bleeding

Blood clotting is one of the body's oldest survival mechanisms-a biological defense that has protected humans from dangerous bleeding for millions of years.

But when severe injuries strike, nature's solution can sometimes fall short.

Now, researchers in the Paul M. Rady Department of Mechanical Engineering at CU Boulder are helping test a new type of engineered blood clot that forms faster and is more durable than the ones found in nature. The new technique could one day transform how doctors treat traumatic injuries and manage life-threatening blood loss.

This is a new biomaterial with the potential to save many lives."

Rong Long, Associate Professor, CU Boulder 

The work, recently published in the journal Nature, was led by Associate Professor Jianyu Li in the Laboratory of Biomaterials Mechanics at McGill University. Long and his group, along with researchers from the University of British Columbia, the University of Toronto and the Versiti Blood Research Institutes, were contributing authors in the study.

The manufactured clots are built from red blood cells. By rapidly linking the blood cells into durable networks, the multi-university team created a reinforced blood clot that forms faster and is far stronger than the body's natural version. 

Long and his team in the Nonlinear Mechanics Laboratory helped uncover the mechanical principles behind the engineered clot, using computational models and tests to study its properties. The testing demonstrated how much pressure the engineered clot could withstand, as well as its strength and how fast it formed. 

"We found the material to be 13 times tougher and four times more adhesive than native blood clots," Long said.

Strengthening nature's first responders

Blood clots tend to have a bad reputation. When they form in the wrong place or abnormally, they can lead to serious medical emergencies such as strokes and heart attacks. 

However, blood clotting is crucial in many situations, from a cut finger in the kitchen to a scraped knee from a bike fall.

Even during these routine situations, blood clotting is what prevents excessive blood loss. But according to the new study, that natural response isn't always fast or effective enough for more severe circumstances.

"There's a protein called fibrin. When we bleed, platelets and fibrin form a network to help seal the wound," said Long. "These native blood clots are impressive, but they are brittle and slow to form. A soldier dealing with a gunshot wound or a patient experiencing a hemorrhage needs faster clotting that is more resistant to rupture." 

One day, Li-the senior author of the study- shared with Long a bold idea.

Li, alongside first author Shuaibing Jiang, a PhD student in Li's lab and now a postdoctoral associate at Harvard Medical School, showed Long a new type of blood clot that uses a novel technique to reinforce natural clots with a second network of red blood cells.

The natural and reinforced networks combined to create an engineered clotting system tougher and faster than any natural blood clot seen before.

"It was so exciting," Long said. "From there, we began building models and studying the mechanics behind this incredible material."

Creating a new biomaterial

The technique, otherwise known as "click clotting," uses a special chemical reaction to link red blood cells into a gel-like structure. 

Because the reaction doesn't interfere with normal blood chemistry, it can work alongside the body's natural clotting process. This allows the cell-based gel network to act as a second support system layered on top of the body's natural fibrin-platelet clot.

During laboratory tests and live experiments on rodents, the strengthened clots absorbed stress by dissipating energy, rapidly stopping bleeding and preventing the clot from breaking apart. They also formed extremely fast, taking shape in just five seconds. 

But perhaps the most intriguing aspect of the click-clotted clots is their biocompatibility. 

Previous efforts to recreate blood clots often used polymers and other synthetic materials foreign to the body. However, Li's cytogel clots are built from red blood cells-the body's own cellular building blocks.

That natural composition gives the engineered clots a unique advantage: they can easily degrade over time, transforming the stigma of blood clots from risky medical hazards into controlled, life-saving biomaterials.

"Blood cells have an 'expiration date.' Over time, they die just as all life eventually does," said Long. "Using red blood cells as the foundation of these reinforced clots makes them temporary. They can naturally break down in a short time, preventing blockages and other health issues that occur when they are in the body for too long."

During testing, the bio-safe clots showcased a unique ability to support tissue healing and reduce inflammation, as well. Long says these characteristics have great potential in areas such as wound healing and emergency bleeding treatment, with possible applications in trauma care and operating rooms worldwide.

But the researchers also believe the strategy of linking cells together could extend far beyond just blood clots.

Long envisions a day where Li's technology can be used to repair defected tissue or target localized areas of the body for drug delivery and treatment. And while the work is still in its early stages, the team thinks it points toward a broader shift in how biological materials can be engineered for medicine.

"Our work shows that, when engineered appropriately, red blood cells can play a central structural role, enabling the design of stronger and more functional biomaterials," said Li in a news release by McGill University.