Oct. 5, 2005 — Biomedical engineers at Washington Universityin St. Louis have found a new role for the blood protein serum amyloidP in the body's response to medical materials, which may help toexplain a variety of problems associated with heart-lung bypass,hemodialysis and the use of artificial vascular grafts.
Using atechnique called proteomics, the researchers identified many of theblood proteins that stick (adsorb) to the surfaces of medical devices.Blood proteins that adsorb to the surfaces of materials unfold and canbe recognized by the body, which then mounts a response against thedevice. The body's response to adsorbed proteins contributes to avariety of problems, including the formation of small clots that mayclose off small diameter vascular grafts or break away to end up in thelungs, kidney or brain.
Previously, the study of blood proteinson the surfaces of medical devices has been limited by the large numberof unique proteins in the blood -- greater than 150 -- as well as theextremely small amounts of proteins adsorbed on the materials. Forexample, the amount of protein that might adsorb to one side of aquarter is about a millionth of a gram.
Donald Elbert, Ph.D.,Washington University assistant professor of biomedical engineering,used advanced protein separations and mass spectrometry to track theproteins on the surfaces of various polymers used in medical devices.The analysis techniques, collectively called 'proteomics,' are mostoften used to study protein expression in cells.
"The techniquesare extremely sensitive and are really well-suited to studying proteinson surfaces," said Elbert. "Using these techniques, we can in principleidentify a protein given only a billionth of a gram of the protein,even if the protein were mixed with many other types of proteins."
Elbertand his colleagues Jinku Kim and Evan Scott were able to follow theadsorption of multiple blood proteins on the surface of a biomaterialover time.
"Traditionally, most studies were limited to the 'big three' proteins in blood - albumin, fibrinogen and IgG", Elbert said.
The results were published in the Oct. 1, 2005 issue of the Journal of Biomedical Materials Research.
New role for serum amyloid P
Bycasting a wider net, they found one particular protein on the materialsin large amounts, serum amyloid P. Serum amyloid P is very similar instructure to C-reactive protein, a well-known marker for cardiovasculardisease. Normally, serum amyloid P is involved in the clearance of DNAthat is released from dying cells, protecting the individual fromauto-immune disorders.
"No one had ever observed serum amyloid Pon biomedical materials before, because, unless you were specificallylooking for them, the technology wasn't around to easily identifyproteins present in such small amounts," Elbert said. "No one,including us, had ever posed the hypothesis that this protein might beimportant in the biocompatibility of materials. Our results show theimportance of large-scale techniques that emphasize discovery of newknowledge, rather than just hypothesis-testing."
The WashingtonUniversity researchers also found that leukocytes -- white blood cells-- adhered to the serum amyloid P after it adsorbed to surface.Leukocyte adhesion and activation on biomaterials is an important partof the body's response to medical devices. For example, large numbersof activated leukocytes are found stuck to heart-lung bypass machines,and these cells can activate blood clotting. This in turn maycontribute to neurocognitive impairment following the use of thesedevices, possibly due to small clots that break away from the device.
"It'sreally exciting that even after over 60 years of research in the area,there is more to learn about how blood interacts with materials,"Elbert said.
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