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August 29, 2011

Molecular Velcro Stems Bloodflow

ACS Meeting News: Hydrophobically modified chitosan latches onto blood cells and assembles them into a gel

Bethany Halford

Complex Fluids
Watch hm-chitosan transform liquid blood into a gel.
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A new type of bandage, made with a chemically modified version of the polysaccharide chitosan, may offer an inexpensive way to speed up wound healing in trauma centers and on the battlefield, according to work presented at this week’s American Chemical Society national meeting in Denver

When a wound starts to bleed, the protein fibrin assembles into a network at the point of injury, transforming liquid blood into a clot. Now, a team led by University of Maryland chemical and biomolecular engineering professor Srinivasa R. Raghavan has developed a biopolymer that does essentially the same thing.

By attaching benzene-n-octadecyl tails to the backbone of the polysaccharide chitosan, Raghavan’s group created an amphiphilic biopolymer dubbed hm-chitosan. “My interest was to study how polymers with ampiphilic properties would self-assemble in water,” Raghavan tells C&EN, but when the group added the biopolymer to a solution of vesicles it immediately formed a gel. They wondered if the same thing would happen if they added the hm-chitosan to blood.

“The phenomenon of gelling blood is similar to the clotting of blood,” Raghavan explains. Indeed, when they added the hm-chitosan to thinned blood, it immediately thickened into a gel. Blood treated with unmodified chitosan did not gel. “We immediately knew that we had something special,” he says.

Raghavan believes that the hydrophobic tails of the hm-chitosan hook into the cell membranes of blood cells and platelets via hydrophobic interactions, causing the cells to clump together. He likens the phenomenon to a nanoscale version of Velcro, which fastens to a looped fabric by virtue of tiny hooks.

The researchers used the hm-chitosan to treat wounds in rats and made a bandage with the material that was used to heal life-threatening lesions on pigs.

What’s more, the gelling process is reversible. When α-cyclodextrin is added to the gelled blood, the hydrophobic tail will preferentially bind within the hydrophobic cavity of the α-cyclodextrin, causing the blood to liquefy again. This reversibility could make hm-chitosan useful during surgery, where it could be used to stem uncontrolled bleeding while at the same time ensuring that undesired clots can be reversed and thus do not propagate and cause strokes.

“A blood clot is one of the most sophisticated and smart biomaterials known,” comments Christian Kastrup, a biochemistry professor at the University of British Columbia. “Coagulation is notoriously difficult to control, and both bleeding and unwanted coagulation are common causes of death.

“Raghavan and coworkers have developed a novel and effective way to control bleeding using biopolymers that gently induce self-assembly of blood cells.  Their cell-cross-linking strategy has important advances over previously developed hemostatic agents in that it is inexpensive and controllably reversible,” Kastrup says.

Raghavan and his former student Matthew Dowling set up a company, Remedium Technologies, to commercialize the technology. Dowling is its CEO. Raghavan presented the work on Aug. 29, during a symposium in the Division of Polymeric Materials: Science & Engineering and published an account in Biomaterials (DOI: 10.1016/j.biomaterials.2010.12.033) earlier this year.

Chemical & Engineering News
ISSN 0009-2347
Copyright © 2011 American Chemical Society
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