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Synthetic platelets
have been developed by UC Santa Barbara researchers, in collaboration
with researchers at Scripps Research Institute and Sanford-Burnham
Institute in La Jolla, Calif. Their findings are published in the
journal Advanced Materials in a paper titled “Platelet Mimetic Particles
for Targeting Thrombi in Flowing Blood.”
Platelets
are the components of blood that allow it to prevent excessive bleeding
and to heal wounds. The unique physical and biochemical properties of
platelets play an important role in performing these complex biological
tasks. Smaller than red blood cells, platelets are flexible, disk-shaped
cells that are 2-4 micrometers in size.
“Upon
further optimization and exhaustive testing, the synthetic platelets
could be used for various biomedical applications,” said the paper’s
first author Nishit Doshi, a researcher from the Department of Chemical
Engineering.
The
challenge Doshi and colleagues faced was to develop a comparably sized
particle—roughly 1/50th of the diameter of a strand of hair—that had key
structural properties of real platelets.
“In
order to mimic the size, shape, and surface functionality of natural
platelets synthetically, polymeric particles are particularly
attractive,” said Doshi. “However, polymeric particles are orders of
magnitude more rigid than platelets.”
To
solve the problem of flexibility, researchers at UC Santa Barbara used a
polymeric “template”—a core upon which layers of proteins and
polyelectrolytes were deposited, layered, and crosslinked to create a
stable synthetic platelet-shaped particle. The rigid polymeric core was
then dissolved to give the particle the desired flexibility. The
particle was then coated with proteins found on the surface of activated
natural platelets or damaged blood vessels, a procedure performed by
the researchers at Scripps Research Institute.
These
synthetic platelets may be used to not only perform the typical
functions of human platelets; but may also be used to carry imaging
agents to identify damaged blood vessels or to deliver drugs that
dissolve blood clots.
The
synthetic platelets represent the latest and one of the most advanced
in a line of efforts over the last century to mimic platelet function.
While clotting factors and platelets from outside donors are used widely
to halt bleeding, immune system responses and thrombosis have been
issues. Non-platelet-derived substitutes have also received attention;
however, said Doshi, these do not resemble the physical features of
natural platelets.
“This
development is a significant milestone in the field of biomimetic
materials,” said Samir Mitragotri, professor of chemical engineering,
director of UC Santa Barbara’s Center for Bioengineering, and an author
of the paper. “By capitalizing on our capabilities in engineering
materials, with the expertise in platelet biology that exists in
Professor Ruggeri’s laboratory, our synthetic platelets combine unique
physical and biological attributes that mimic natural platelets.”
Biomaterials
research is one of the principal focus areas in UCSB’s Center for
BioEngineering. In 2009, Doshi and colleagues in the Mitragotri
laboratory developed synthetic red blood cells.
“This
work is a marvelous demonstration of the power of material synthesis
applied to medical problems. The synthetic platelets can have profound
implications in wound-healing problems for trauma and wounds arising in
both battlefield situations and during surgery,” said Frank Doyle,
director of UCSB’s Institute of Collaborative Biotechnologies and the
Associate Dean of Research of UCSB’s College of Engineering.
Other
authors of the study include Jennifer N. Orje, Blanca Molins, and
Zaverio Ruggeri from Scripps Research Institute; and Jeffrey Smith from
Sanford-Burnham Medical Research Institute.
This
work was funded by the Institute for Collaborative Biotechnologies
through a grant from the U.S. Army Research Office and the National
Institutes of Health.