With this limitation in mind, the researchers investigated ways to use growth factor efficiently. They hit on a molecule called heparin, one of the molecules that bonds growth factor to its receptor on the cell's surface. When heparin binds to the receptor and the growth factor, it actually increases the activity of growth factor and stabilizes it.
"Our idea was, 'Let's use heparin as is, without any modification, to stabilize the growth factor and also to present it to the receptor,' " says Wang.
But there was only one catch: If you bond heparin to growth factor, the resulting substance is water-soluble. Injected into the body, the complex dissolves within seconds. We are made mostly of water, after all.
The team had to figure out a way to keep the complex from dissolving long enough for it to do its work of regenerating blood vessels.
The trick, they discovered, was to use a polycationa molecule with multiple positive charges. Heparin has many negative charges. If it's neutralized with a polycation, it can be brought out of solution into what is called a coacervatean aggregate of tiny oil droplets. Many other research teams use heparin in growth factor delivery as well, but the Wang lab is the first to convert the heparin/growth factor complexes into coacervates.
In this first-ever report of using coacervate for the controlled delivery of growth factor, the team delivered fibroblast growth factor-2. This led to extensive and persistent new blood vessel formation. The team used only one growth factor to induce the formation of mature blood vessels. These vessels were stabilized by special cells called mural cells.
Now, Wang has gone on to use his unique delivery platform to study the controlle
|Contact: Karen Hoffmann|
University of Pittsburgh