Bold science, new blood

By Harlan Spector Photos by Lillian Messner

After he arrived at Case Western Reserve University as a biomedical engineering research associate in 2003, Anirban Sen Gupta, PhD, fixed his attention on the biology of blood platelets and how they could be used to save lives. If only there were a plentiful supply, readily available.

People who suffer traumatic injuries from car accidents, gunshots and the like often don’t receive life-saving blood and platelet transfusions in time. It’s essentially a logistics and supply challenge. Donor platelets — the blood cells that help the body to form clots and stanch bleeding — are always in short supply.

Now a professor of biomedical engineering, Sen Gupta is leading the quest toward a solution. He and his team have developed synthetic platelets that mimic clotting mechanisms of real platelets and amplify the body’s natural ability to stop the bleeding. The patented technology, named SynthoPlate for commercialization purposes, is seen by some as a game changer.

“There are thousands of lives that could be saved each year, and that’s just for trauma,” said Dr. Philip Spinella, a trauma physician at St. Louis Children's Hospital and one of the world’s leading experts on clinical trials of blood products. “That’s why this technology is so exciting.”

An estimated 60,000 people die each year in the United States from hemorrhaging, a leading cause of death in trauma

cases. If successful, synthetic platelets could help stop bleeding from traumatic injuries, complex surgeries and other causes such as clotting disorders, Spinella said.

Studies show if you can transfuse blood or blood components soon after trauma, the chances of survival increase tremendously. This is why oftentimes death from traumatic hemorrhage is considered a preventable death.

Platelets, tiny blood cells, are part of the body’s rapid defense force. They rush to a wound to form a plug and stop bleeding. Made in the bone marrow, platelets can be transfused as part of whole blood or as a separate component along with red blood cells and plasma.

The problem is that platelets for transfusion are hard to find and hard to keep. They are highly perishable and are typically available only at large hospitals or trauma centers.

The artificial platelets being developed in Sen Gupta’s lab on Case Quad could enable transfusions in smaller hospitals, at roadside accidents and on the battle field, where real platelets are almost never available.

This is a prime motivation for the young researcher.

“If you can make something that works like platelets but has easier availability and longer shelf-life, you can revolutionize how trauma patients are treated,” Sen Gupta said. “You could save the patient on the roadside or in a remote hospital.”

Some of the advantages of artificial platelets include: • They are portable, long-lasting and do not require blood typing • They can be manufactured on a large scale • They can be sterilized to resist bacterial contamination

• They can be injected directly into a vein at the scene of trauma

As chief research officer of Haima Therapeutics, Christa Pawlowski ’11, PhD ’15, is working to commercialize her former professor’s technology.

Sen Gupta holds a vial of human platelet-rich plasma, which he tests against synthetic platelet particles to see cooperative activity.

In contrast, donor-derived blood platelets are highly susceptible to contamination, which limits their shelf life to 5-7 days.

In Sen Gupta’s research, some see the intersection of a societal need and Case expertise.

Sen Gupta is collaborating with researchers who are manufacturing artificial red blood cells. He envisions the artificial platelets and red blood cells combining in plasma to create the world’s first biosynthetic whole blood surrogate.

“If they solve that problem, they basically revolutionize emergency medicine,” said Christian Zorman, PhD, the Associate Dean of Research at the Case School of Engineering. “The reason this fits really well with Case is that it’s at the intersection of biomedical engineering and materials science, two areas where we are very strong.”

Since opening his lab in 2006, Sen Gupta has attracted about $11 million in funding from the National Institutes of Health and the U.S. Department of Defense. In 2018, he and former student Christa Pawlowski ’11, PhD ’15, co-founded Haima Therapeutics. Their startup, located in the BioEnterprise building near campus, taps separate government grants and private investment as it seeks to bring SynthoPlate to market.

“We want to make sure this can be used by people and save people’s lives,” said Pawlowski, the company’s chief scientific officer. “How do we make this into a product that can be manufactured?”

Haima is now designing the initial product and seeking private investment to fund clinical trials, an essential step toward FDA approval of a new drug. Plenty are watching and hoping.

The military has keen interest in technologies to control bleeding. A 2013 study of military casualties in Iraq and Afghanistan found uncontrolled blood loss was the leading cause of death in 90 percent of potentially survivable battlefield cases.

As a U.S. Army veteran, Dr. Spinella saw the carnage firsthand. Before becoming a professor at Washington University School of Medicine in St. Louis, he was an Army doctor deployed to the Iraq War from 2004 to 2005.

“I saw plenty of people bleeding,” said Spinella. “We were using whole blood collected on site. The problem with that is you need to have thousands of donors. Eventually, you run out of donors.”

When he came home from the war, Spinella began to focus on blood solutions. Two years ago, he met Sen Gupta at a medical conference sponsored by the Department of Defense. In August, he joined his research team as a scientific advisor.

Now being tested on animals, Sen Gupta’s synthetic platelets are potentially three to four years away from human trials. But Spinella has high hopes.

The platelets can be freeze dried, he noted, making them easy to preserve and rushed to a scene.

“It can easily be put on ambulances and helicopters,” he added.

Sen Gupta began exploring artificial blood platelets as a research assistant in the Department of Biomedical Engineering. He now has his own lab in the Wickenden Building.

That would allow first responders to begin lifesaving treatments on the scene.

“This is potentially part of the solution,” he said. “My hope is that it can get licensed and begin to reduce death from hemorrhage.”

Sen Gupta’s interest in the field started at Case when, as a research associate, he studied polymer-based coatings designed to prevent blood clotting on medical devices. Drawn to Case for its biomedical engineering program and translational research environment, he dug deep into the complex processes of blood clotting. He found studies of artificial platelets from the 1980s and 90s, and learned that the designs had not advanced into effective technologies.

“This made me curious to know the reason,” he said.

He found that the past designs didn’t mimic platelets, but mimicked a molecule called fibrinogen, a protein that promotes clotting.

“This led me to coming up with a new design that closely mimics how platelets actually do their clotting function,” he said.

The American Heart Association endorsed his idea with an early career research grant in 2007.

“That started my journey into the world of synthetic platelets,” he said.

Born and raised in Kolkata (formerly Calcutta), India, Sen Gupta came to America as a graduate student in 1998. He studied at the University of Akron, where he received his master’s degree and doctorate with a focus on polymeric biomaterials engineering.

About 15 students now work in his labs in the Wickenden Building, but Sen Gupta’s work has also drawn collaborators from the University of Pittsburgh, the University of North Carolina, Harvard University and several other institutions in the U.S. and Europe. The Biomedical Advanced Research and Development Authority, a government bio-defense agency, has expressed interest in the potential of synthetic platelets to treat clotting dysfunctions caused by radiation poisoning.

While his primary focus has been stemming blood loss from trauma, Sen Gupta is also researching artificial platelets as a targeted drug delivery system to treat patients with cardiovascular diseases and cancer — even to treat patients in other worlds.

Sen Gupta and colleagues have discussed whether astronauts might one day stow artificial platelets on missions to Mars.

“There is no blood product that goes to space,” he observed. “If you have colonies in space, you will have injuries in space.”

Harlan Spector, a Cleveland freelance writer, was an award-winning healthcare reporter for The Plain Dealer.

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