Article Type
Changed
Tue, 09/09/2014 - 05:00
Display Headline
Synthetic platelets can augment natural clotting

Thomas Barker, PhD, with

bacteria needed to create

the platelet-like particles

Credit: Gary Meek

Researchers say they’ve developed a new class of synthetic platelet-like particles that can augment natural blood clotting.

The particles are based on soft and deformable hydrogel materials and measure about 1 micron in diameter.

Testing in animal models and a simulated circulatory system suggested the particles are effective at slowing bleeding and can safely circulate in the bloodstream.

The particles have been tested in human blood but not in clinical trials.

Ashley Brown, PhD, of the Georgia Institute of Technology and Emory University in Atlanta, and her colleagues described the research involving these particles in Nature Materials.

The team noted that, when fibrinogen proteins receive the right signals from thrombin, they polymerize at the site of bleeding to form a clot. The synthetic platelet-like particles use the same trigger, so they are activated only when the body’s natural clotting process is initiated.

To create that trigger, the researchers employed molecular evolution. They developed an antibody that could be attached to the hydrogel particles to change their form when they encounter thrombin-activated fibrin. The resulting antibody has a high affinity for the polymerized form of fibrin and a low affinity for the precursor material.

“Fibrin production is on the back end of the clotting process, so we feel that it is a safer place to try to interact with it,” said study author Thomas Barker, PhD, of Georgia Tech and Emory University.

“The specificity of this material provides a very important advantage in triggering clotting at just the right time.”

The researchers tested the platelet-like particles in an animal model and a microfluidic chamber designed to simulate conditions within the body’s circulatory system.

The team used the chamber to study normal human blood, as well as blood that had been depleted of its natural platelets. In platelet-rich blood, clots formed as expected, and blood without platelets did not form clots. When the platelet-like particles were added to the platelet-depleted blood, it was able to clot.

The researchers also tested blood from infants who had received anticoagulant treatment prior to undergoing open heart surgery. When platelet-like particles were added to this blood, it was able to form clots.

Finally, the team performed safety testing on blood from hemophilia patients. Because their blood lacked the triggers needed to cause fibrin formation, the particles had no effect.

What ultimately happens to the particles circulating in the bloodstream will be the topic of future research, Dr Brown said. Particles of similar size and composition are normally eliminated from the body.

While the platelet-like particles lack many features of natural platelets, the researchers were surprised to find one property in common. Clots formed by natural platelets begin to contract over a period of hours, beginning the body’s repair process. Clots formed from the synthetic particles also contract, but over a longer period of time.

These particles were originally developed to be used on the battlefield by wounded soldiers, who might self-administer them using a device about the size of a smartphone. But the researchers believe the particles could also reduce the need for platelet transfusions in patients undergoing chemotherapy or bypass surgery, and in those with certain blood disorders.

“For a patient with insufficient platelets due to bleeding or an inherited disorder, physicians often have to resort to platelet transfusions, which can be difficult to obtain,” said study author Wilbur Lam, MD, PhD, of the Georgia Institute of Technology and Emory University.

“These particles could potentially be a way to obviate the need for a transfusion. Though they don’t have all the assets of natural platelets, a number of intriguing experiments have shown that the particles help augment the clotting process.”

Publications
Topics

Thomas Barker, PhD, with

bacteria needed to create

the platelet-like particles

Credit: Gary Meek

Researchers say they’ve developed a new class of synthetic platelet-like particles that can augment natural blood clotting.

The particles are based on soft and deformable hydrogel materials and measure about 1 micron in diameter.

Testing in animal models and a simulated circulatory system suggested the particles are effective at slowing bleeding and can safely circulate in the bloodstream.

The particles have been tested in human blood but not in clinical trials.

Ashley Brown, PhD, of the Georgia Institute of Technology and Emory University in Atlanta, and her colleagues described the research involving these particles in Nature Materials.

The team noted that, when fibrinogen proteins receive the right signals from thrombin, they polymerize at the site of bleeding to form a clot. The synthetic platelet-like particles use the same trigger, so they are activated only when the body’s natural clotting process is initiated.

To create that trigger, the researchers employed molecular evolution. They developed an antibody that could be attached to the hydrogel particles to change their form when they encounter thrombin-activated fibrin. The resulting antibody has a high affinity for the polymerized form of fibrin and a low affinity for the precursor material.

“Fibrin production is on the back end of the clotting process, so we feel that it is a safer place to try to interact with it,” said study author Thomas Barker, PhD, of Georgia Tech and Emory University.

“The specificity of this material provides a very important advantage in triggering clotting at just the right time.”

The researchers tested the platelet-like particles in an animal model and a microfluidic chamber designed to simulate conditions within the body’s circulatory system.

The team used the chamber to study normal human blood, as well as blood that had been depleted of its natural platelets. In platelet-rich blood, clots formed as expected, and blood without platelets did not form clots. When the platelet-like particles were added to the platelet-depleted blood, it was able to clot.

The researchers also tested blood from infants who had received anticoagulant treatment prior to undergoing open heart surgery. When platelet-like particles were added to this blood, it was able to form clots.

Finally, the team performed safety testing on blood from hemophilia patients. Because their blood lacked the triggers needed to cause fibrin formation, the particles had no effect.

What ultimately happens to the particles circulating in the bloodstream will be the topic of future research, Dr Brown said. Particles of similar size and composition are normally eliminated from the body.

While the platelet-like particles lack many features of natural platelets, the researchers were surprised to find one property in common. Clots formed by natural platelets begin to contract over a period of hours, beginning the body’s repair process. Clots formed from the synthetic particles also contract, but over a longer period of time.

These particles were originally developed to be used on the battlefield by wounded soldiers, who might self-administer them using a device about the size of a smartphone. But the researchers believe the particles could also reduce the need for platelet transfusions in patients undergoing chemotherapy or bypass surgery, and in those with certain blood disorders.

“For a patient with insufficient platelets due to bleeding or an inherited disorder, physicians often have to resort to platelet transfusions, which can be difficult to obtain,” said study author Wilbur Lam, MD, PhD, of the Georgia Institute of Technology and Emory University.

“These particles could potentially be a way to obviate the need for a transfusion. Though they don’t have all the assets of natural platelets, a number of intriguing experiments have shown that the particles help augment the clotting process.”

Thomas Barker, PhD, with

bacteria needed to create

the platelet-like particles

Credit: Gary Meek

Researchers say they’ve developed a new class of synthetic platelet-like particles that can augment natural blood clotting.

The particles are based on soft and deformable hydrogel materials and measure about 1 micron in diameter.

Testing in animal models and a simulated circulatory system suggested the particles are effective at slowing bleeding and can safely circulate in the bloodstream.

The particles have been tested in human blood but not in clinical trials.

Ashley Brown, PhD, of the Georgia Institute of Technology and Emory University in Atlanta, and her colleagues described the research involving these particles in Nature Materials.

The team noted that, when fibrinogen proteins receive the right signals from thrombin, they polymerize at the site of bleeding to form a clot. The synthetic platelet-like particles use the same trigger, so they are activated only when the body’s natural clotting process is initiated.

To create that trigger, the researchers employed molecular evolution. They developed an antibody that could be attached to the hydrogel particles to change their form when they encounter thrombin-activated fibrin. The resulting antibody has a high affinity for the polymerized form of fibrin and a low affinity for the precursor material.

“Fibrin production is on the back end of the clotting process, so we feel that it is a safer place to try to interact with it,” said study author Thomas Barker, PhD, of Georgia Tech and Emory University.

“The specificity of this material provides a very important advantage in triggering clotting at just the right time.”

The researchers tested the platelet-like particles in an animal model and a microfluidic chamber designed to simulate conditions within the body’s circulatory system.

The team used the chamber to study normal human blood, as well as blood that had been depleted of its natural platelets. In platelet-rich blood, clots formed as expected, and blood without platelets did not form clots. When the platelet-like particles were added to the platelet-depleted blood, it was able to clot.

The researchers also tested blood from infants who had received anticoagulant treatment prior to undergoing open heart surgery. When platelet-like particles were added to this blood, it was able to form clots.

Finally, the team performed safety testing on blood from hemophilia patients. Because their blood lacked the triggers needed to cause fibrin formation, the particles had no effect.

What ultimately happens to the particles circulating in the bloodstream will be the topic of future research, Dr Brown said. Particles of similar size and composition are normally eliminated from the body.

While the platelet-like particles lack many features of natural platelets, the researchers were surprised to find one property in common. Clots formed by natural platelets begin to contract over a period of hours, beginning the body’s repair process. Clots formed from the synthetic particles also contract, but over a longer period of time.

These particles were originally developed to be used on the battlefield by wounded soldiers, who might self-administer them using a device about the size of a smartphone. But the researchers believe the particles could also reduce the need for platelet transfusions in patients undergoing chemotherapy or bypass surgery, and in those with certain blood disorders.

“For a patient with insufficient platelets due to bleeding or an inherited disorder, physicians often have to resort to platelet transfusions, which can be difficult to obtain,” said study author Wilbur Lam, MD, PhD, of the Georgia Institute of Technology and Emory University.

“These particles could potentially be a way to obviate the need for a transfusion. Though they don’t have all the assets of natural platelets, a number of intriguing experiments have shown that the particles help augment the clotting process.”

Publications
Publications
Topics
Article Type
Display Headline
Synthetic platelets can augment natural clotting
Display Headline
Synthetic platelets can augment natural clotting
Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME
Disqus Comments
Default
Use ProPublica