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Credit: Andre E.X. Brown
Artificial platelet mimics can halt bleeding in mouse models 65% faster than nature can on its own, a new study has shown.
These platelet-like nanoparticles (PLNs) mimic the shape, size, flexibility, and surface chemistry of real blood platelets.
Researchers believe these design factors together are important for inducing clots to form faster at vascular injury sites while preventing harmful clots from forming indiscriminately elsewhere in the body.
The new technology is reported in ACS Nano.
Study investigator Anirban Sen Gupta, PhD, of Case Western Reserve in Cleveland, Ohio, previously designed peptide-based surface chemistries that mimic the clot-relevant activities of real platelets.
Building on this work, Dr Sen Gupta has now focused on incorporating morphological and mechanical cues that are naturally present in platelets to further refine the design.
“Morphological and mechanical factors influence the margination of natural platelets to the blood vessel wall, and only when they are near the wall can the critical clot-promoting chemical interactions take place,” he said.
These natural cues motivated Dr Sen Gupta to team up with Samir Mitragotri, PhD, of the University of California Santa Barbara, whose lab recently developed albumin-based technologies to make particles that mimic the geometry and mechanical properties of red blood cells and platelets.
Together, the researchers developed PLNs that combine morphological, mechanical, and surface chemical properties of natural platelets.
The team believes this refined design will be able to simulate natural platelet’s ability to collide effectively with larger and softer red blood cells in systemic blood flow. The collisions cause margination—pushing the platelets out of the main flow and closer to the blood vessel wall—increasing the probability of interacting with an injury site.
The surface coatings enable the PLNs to anchor to injury-site-specific proteins, von Willebrand factor and collagen, while inducing the natural and artificial platelets to aggregate faster at the injury site.
When the researchers injected the PLNs in mice, the artificial platelets formed clots at the site of injury 3 times faster than natural platelets alone in control mice.
The ability to interact selectively with injury site proteins, as well as the ability to remain mechanically flexible like natural platelets, enables these PLNs to safely ride through the smallest of blood vessels without causing unwanted clots. PLNs that don’t aggregate in a clot and continue to circulate are metabolized in 1 to 2 days.
The researchers believe their new artificial platelet design may be even more effective in larger-volume blood flows, where margination to the blood vessel wall is more prominent. They expect to soon begin testing those capabilities.
If the PLNs prove effective in humans, they could be used to stem bleeding in patients with clotting disorders, those suffering from traumatic injury, and patients undergoing surgeries.
The technology might also be used to deliver drugs to target sites in patients suffering from atherosclerosis, thrombosis, or other platelet-involved pathologic conditions. Dr Sen Gupta believes the PLNs could even be used to deliver cancer drugs to metastatic tumors that have high platelet interactions. 
Credit: Andre E.X. Brown
Artificial platelet mimics can halt bleeding in mouse models 65% faster than nature can on its own, a new study has shown.
These platelet-like nanoparticles (PLNs) mimic the shape, size, flexibility, and surface chemistry of real blood platelets.
Researchers believe these design factors together are important for inducing clots to form faster at vascular injury sites while preventing harmful clots from forming indiscriminately elsewhere in the body.
The new technology is reported in ACS Nano.
Study investigator Anirban Sen Gupta, PhD, of Case Western Reserve in Cleveland, Ohio, previously designed peptide-based surface chemistries that mimic the clot-relevant activities of real platelets.
Building on this work, Dr Sen Gupta has now focused on incorporating morphological and mechanical cues that are naturally present in platelets to further refine the design.
“Morphological and mechanical factors influence the margination of natural platelets to the blood vessel wall, and only when they are near the wall can the critical clot-promoting chemical interactions take place,” he said.
These natural cues motivated Dr Sen Gupta to team up with Samir Mitragotri, PhD, of the University of California Santa Barbara, whose lab recently developed albumin-based technologies to make particles that mimic the geometry and mechanical properties of red blood cells and platelets.
Together, the researchers developed PLNs that combine morphological, mechanical, and surface chemical properties of natural platelets.
The team believes this refined design will be able to simulate natural platelet’s ability to collide effectively with larger and softer red blood cells in systemic blood flow. The collisions cause margination—pushing the platelets out of the main flow and closer to the blood vessel wall—increasing the probability of interacting with an injury site.
The surface coatings enable the PLNs to anchor to injury-site-specific proteins, von Willebrand factor and collagen, while inducing the natural and artificial platelets to aggregate faster at the injury site.
When the researchers injected the PLNs in mice, the artificial platelets formed clots at the site of injury 3 times faster than natural platelets alone in control mice.
The ability to interact selectively with injury site proteins, as well as the ability to remain mechanically flexible like natural platelets, enables these PLNs to safely ride through the smallest of blood vessels without causing unwanted clots. PLNs that don’t aggregate in a clot and continue to circulate are metabolized in 1 to 2 days.
The researchers believe their new artificial platelet design may be even more effective in larger-volume blood flows, where margination to the blood vessel wall is more prominent. They expect to soon begin testing those capabilities.
If the PLNs prove effective in humans, they could be used to stem bleeding in patients with clotting disorders, those suffering from traumatic injury, and patients undergoing surgeries.
The technology might also be used to deliver drugs to target sites in patients suffering from atherosclerosis, thrombosis, or other platelet-involved pathologic conditions. Dr Sen Gupta believes the PLNs could even be used to deliver cancer drugs to metastatic tumors that have high platelet interactions.
Credit: Andre E.X. Brown
Artificial platelet mimics can halt bleeding in mouse models 65% faster than nature can on its own, a new study has shown.
These platelet-like nanoparticles (PLNs) mimic the shape, size, flexibility, and surface chemistry of real blood platelets.
Researchers believe these design factors together are important for inducing clots to form faster at vascular injury sites while preventing harmful clots from forming indiscriminately elsewhere in the body.
The new technology is reported in ACS Nano.
Study investigator Anirban Sen Gupta, PhD, of Case Western Reserve in Cleveland, Ohio, previously designed peptide-based surface chemistries that mimic the clot-relevant activities of real platelets.
Building on this work, Dr Sen Gupta has now focused on incorporating morphological and mechanical cues that are naturally present in platelets to further refine the design.
“Morphological and mechanical factors influence the margination of natural platelets to the blood vessel wall, and only when they are near the wall can the critical clot-promoting chemical interactions take place,” he said.
These natural cues motivated Dr Sen Gupta to team up with Samir Mitragotri, PhD, of the University of California Santa Barbara, whose lab recently developed albumin-based technologies to make particles that mimic the geometry and mechanical properties of red blood cells and platelets.
Together, the researchers developed PLNs that combine morphological, mechanical, and surface chemical properties of natural platelets.
The team believes this refined design will be able to simulate natural platelet’s ability to collide effectively with larger and softer red blood cells in systemic blood flow. The collisions cause margination—pushing the platelets out of the main flow and closer to the blood vessel wall—increasing the probability of interacting with an injury site.
The surface coatings enable the PLNs to anchor to injury-site-specific proteins, von Willebrand factor and collagen, while inducing the natural and artificial platelets to aggregate faster at the injury site.
When the researchers injected the PLNs in mice, the artificial platelets formed clots at the site of injury 3 times faster than natural platelets alone in control mice.
The ability to interact selectively with injury site proteins, as well as the ability to remain mechanically flexible like natural platelets, enables these PLNs to safely ride through the smallest of blood vessels without causing unwanted clots. PLNs that don’t aggregate in a clot and continue to circulate are metabolized in 1 to 2 days.
The researchers believe their new artificial platelet design may be even more effective in larger-volume blood flows, where margination to the blood vessel wall is more prominent. They expect to soon begin testing those capabilities.
If the PLNs prove effective in humans, they could be used to stem bleeding in patients with clotting disorders, those suffering from traumatic injury, and patients undergoing surgeries.
The technology might also be used to deliver drugs to target sites in patients suffering from atherosclerosis, thrombosis, or other platelet-involved pathologic conditions. Dr Sen Gupta believes the PLNs could even be used to deliver cancer drugs to metastatic tumors that have high platelet interactions.