Scientists at Case Western Reserve University and the University of California, Santa Barbara report the development of artificial platelet mimics that halted bleeding in mouse models 65% quicker than if nature was working on its own. The researchers said they integratively mimicked the shape, size, flexibility, and surface chemistry of real blood platelets on albumin-based particle platforms.

They believe these four design factors together are important in inducing clots to form faster selectively at vascular injury sites while preventing harmful clots from forming indiscriminately elsewhere in the body.

The new technology, described in a paper (“Platelet-like Nanoparticles: Mimicking Shape, Flexibility, and Surface Biology of Platelets To Target Vascular Injuries”) in ACS Nano, is aimed at stemming bleeding in patients suffering from traumatic injury, undergoing surgeries or suffering clotting disorders from platelet defects or a lack of platelets. Further, the technology may be used to deliver drugs to target sites in patients suffering atherosclerosis, thrombosis or other platelet-involved pathologic conditions, according to the scientists.

Anirban Sen Gupta, Ph.D., an associate professor of biomedical engineering at Case Western Reserve, previously designed peptide-based surface chemistries that mimic the clot-relevant activities of real platelets. Building on this work, Dr. Sen Gupta now focuses 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.

Dr. Sen Gupta teamed up with Samir Mitragotri, Ph.D., a professor of chemical engineering at UC Santa Barbara, whose laboratory has recently developed albumin-based technologies to make particles that mimic the geometry and mechanical properties of red blood cells and platelets. Together, the team has developed artificial platelet-like nanoparticles (PLNs) that combine morphological, mechanical, and surface chemical properties of natural platelets.

“We show that both the biochemical and biophysical design parameters of PLNs are essential in mimicking platelets and their hemostatic functions,” wrote the investigators. “PLNs offer a nanoscale technology that integrates platelet-mimetic biophysical and biochemical properties for potential applications in injectable synthetic hemostats and vascularly targeted payload delivery.”

The researchers believe their 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 artificial platelets 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.

Testing in mouse models showed that intravenous injection of these artificial platelets formed clots at the site of injury three 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 artificial platelets to safely ride through the smallest of blood vessels without causing unwanted clots.

The researchers believe the 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.

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