Tuesday, October 17, 2006

Clog-busters

A new recipe for artificial blood vessels may help solve a tough clogging problem.

By Susan Nasr

Washington University bioengineers imagine that the gel pictured here will one day solve a clotting problem in small, artificial blood vessels. The gel, made from protein fragments (blue rectangles), the blood protein albumin (gray tufts), a signaling lipid (yellow splotches), and a synthetic polymer (blue stars), would coax endothelial cells (gray lump), which line human blood vessels, to colonize the inside of artificial vessels.

Multimedia •  ANIMATION: Endothelial cells on gel

Small, artificial blood vessels are meant to offer hope to cardiac-bypass patients. The problem is that these tiny synthetic vessels tend to clog. Now, biomedical engineer Donald Elbert and his team at Washington University, in St. Louis, have developed a new material designed to trick the body into building vessels from its own cells.

The root of the clogging problem is thermodynamics, Elbert says. When a vessel is made of modified Teflon--or anything besides the body's own cells--clotting proteins in the blood bump into the vessel walls, stick, unfold, and become active, setting off clotting reactions. The clots are too small to block large vessels, and in fact, Teflon aortas are common. But in vessels narrower than six millimeters across, clots make clogs. Consequently, cardiac-bypass patients can't receive small artificial-vessel implants. Instead, small vessels have to be harvested from the patient's body so that blood can be rerouted. This is an extra surgery, and eventually, the patient may run out of vessels to harvest.

Elbert's solution is a novel coating for the inside of artificial vessels. It's primarily made of substances found in the human body. Polyethylene glycol, the only synthetic ingredient, is a many-armed polymer used in toothpaste and shampoo. When exposed to blood, it repels nearly all clotting proteins that try to stick to it. Albumin, a blood protein, is included to attach polyethylene glycols together. Polyethylene glycol's arms link to two biologically active ingredients. One of the ingredients is a protein fragment that acts like Velcro, binding endothelial cells, which line human blood vessels, to the artificial lining. The other bioactive ingredient is an enzyme found in blood that can grab a fatty substance, or lipid, from the bloodstream and convert it into a lipid called sphingosine-1-phosphate that sends growth and survival signals to endothelial cells.

Making the concoction is "simple," Elbert says. All the ingredients are mixed in water and left overnight. By morning, they form a gel.

Elbert imagines that a synthetic graft lined with the coating could then be sewn into an existing blood vessel. Polyethylene glycol would repel most clotting proteins for some time. Meanwhile, the enzyme would make and release the lipid that signals endothelial cells, encouraging them to grow onto the graft edges. The protein fragments would hold the cells on the surface. The gel would release more lipid, signaling the cells to divide and colonize. "After a month or two, the whole inner surface of the graft would hopefully be lined with a layer of cells," Elbert says. The cells would exude chemicals to hinder clotting, as they do naturally in the body.