Synthetic platelets developed in NC control bleeding in animal models

New research funded in part by the North Carolina Biotechnology Center shows that bioengineered platelets can be used to stop bleeding and enhance wound healing in animal models of trauma.

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Ultimately, the synthetic platelets may hold promise in human medicine as a better alternative to the current medical practice of harvesting platelets from blood donors. The research was published April 10 in the journal Science Translational Medicine by a team of scientists, several of them from three North Carolina universities: North Carolina State University, the University of North Carolina at Chapel Hill and Duke University. Four of the paper’s co-authors are co-founders of SelSym Biotech, a Durham company created in 2019 to commercialize synthetic platelets for clinical use.

Platelet transfusions are often required for patients who have severe bleeding from trauma, are going into surgery or are receiving chemotherapy. Using platelets harvested from blood donors is challenging because platelets have a short shelf life, must be stored under controlled conditions and should be blood typed before use. Therefore, donor platelets are generally not used in point-of-care emergency medicine or carried on ambulances.

“A synthetic platelet like ours – one that is much easier to store and transport than donated blood products and that doesn’t require blood typing prior to use – could be revolutionary for the ambulatory care of trauma patients,” said Ashley Brown, Ph.D., corresponding author of the paper and an associate professor in the joint biomedical engineering program at NC State and UNC. “Additionally, donated platelets are often in short supply, so this technology offers significant potential to improve rescue or even proactive treatment options for clinicians needing to mitigate hemorrhage for their patients undergoing high bleeding risk procedures, such as cardiac surgeries.”

Made with hydrogel nanoparticles

SelSym testing lab
SelSym lab.

The synthetic platelets are made of hydrogel nanoparticles that mimic the size, shape and mechanical properties of human platelets. Hydrogels are water-based gels that are composed of water and a small proportion of polymer molecules.

“Our synthetic platelets are deformable – meaning they can change shape – in the same way that normal platelets are,” Brown said.

The researchers engineered the surface of the synthetic platelets to incorporate antibody fragments that bind to a protein called fibrin. When a body is injured, it synthesizes fibrin at the site of the wound. The fibrin then forms a mesh-like substance to promote blood clotting.

“Because the synthetic platelets are coated with these antibody fragments, the synthetic platelets travel freely through the blood stream until they reach the wound site,” Brown said. “Once there, the antibody fragments bind to the fibrin, and the synthetic platelets expedite the clotting process.”

In addition to forming a clot within the fibrin network, the synthetic platelets act to contract the clot over time, just as natural platelets do.

“This expedites the process of healing, allowing the body to move forward with tissue repair and recovery,” Brown said.

SelSym in vitro testing lab.

The researchers initially demonstrated the efficacy of the antibody fragments via in vitro testing. They also showed that the antibody fragments and synthetic platelets could be produced in quantities viable for large-scale manufacturing.

The researchers then used a mouse model to determine the optimal dose of synthetic platelets necessary to stop bleeding.

Subsequent research in both mouse and pig models demonstrated that the synthetic platelets traveled to the site of a wound, expedited clotting, did not cause any clotting problems in areas outside of the wound, and accelerated healing.

“In the mouse and pig models, healing rates were comparable in animals that received platelet transfusions and synthetic platelet transfusions,” Brown said. “And both groups fared better than animals that did not receive either transfusion. We also found that the animals in both mouse and pig models were able to safely clear the synthetic platelets over time through normal kidney function. We didn’t see any adverse health effects associated with the use of the synthetic platelets.”

Robust research funding

The published research was funded by the National Heart, Lung, and Blood Institute, the National Institute of General Medical Sciences, the National Institutes of Health, the Department of Defense; the National Science Foundation, the American Heart Association, the U.S. Department of Veterans Affairs, NC State’s Chancellor’s Innovation Fund and NCBiotech, through a $110,000 Translational Research Grant. NCBiotech also provided a $100,000 Small Business Research Loan to SelSym in 2022 to support the development of the synthetic platelets, branded as SymClot.

The NCBiotech funding “has been tremendously important for our progress,” Brown said. “The Translational Research Grant helped fund pig studies . . . critical for establishing efficacy in a large animal model. The funds from the loan have been critical in supporting scale-up/manufacturing and regulatory development efforts on the SelSym side.”

The company has also received “significant business development support” through mentorship from NCBiotech’s Entrepreneur in Residence program, she said.

Commercialization plans

Brown is a co-founder of SelSym and is the company’s senior scientific adviser. The other co-founders are Seema Nandi, Ph.D. chief executive officer; Andrew Lyon, Ph.D., chief scientific officer, and Tom Barker, Ph.D., president.

Brown, Lyon and Barker conceived the technology while all were on the research faculty at the Georgia Institute of Technology. Despite then moving to different institutions – Brown to NC State, Lyon to Chapman University and Barker to the University of Virginia – they pursued development of the technology, primarily at NC State.

The technology is jointly owned by NC State, Georgia Tech and UVA through an inter-institutional agreement, and it was licensed to SelSym by NC State with support from the other two schools, Brown said.

SelSym, named for a word interplay of “synthetic” and “cells,” has to date received about $3 million in federal grants to support preclinical development of the technology. The company recently opened a $5 million seed round of funding and expects to close on it by the end of the first quarter of 2025, Brown said.

SelSym is aiming to file an Investigational New Drug application with the U.S. Food and Drug Administration and begin clinical trials within two years, she said.

The total addressable market for the technology in the United States for use in emergent trauma and planned surgical applications is about $20 billion.

“Based on our preliminary estimates, we anticipate that the cost of the synthetic platelets – if they are approved for clinical use – would be comparable to the current cost of platelets,” Brown said.

Barry Teater, NCBiotech Writer
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