Modified Collagen Could Could Help Deliver Drugs And Shape The Growth Of Engineered Tissue

Michael (Seungju) Yu of the university's Whiting School of Engineeringwas scheduled to describe the new collagen modification process and itspotential medical uses in an Aug. 30 presentation in Washington, D.C.,at the 230th annual meeting of the American Chemical Society. His teamalso published a paper on the work earlier this year in the Journal ofthe American Chemical Society.

The research focuses on the human body's most common protein.Collagen promotes blood clotting and provides the sponge-like scaffoldupon which cells build nerves, bones and skin. Because it is non-toxic,dissolves naturally over time and rarely triggers rejection, collagenis commonly used in cosmetics, drug delivery systems and biocompatiblecoatings.

Yu's goal is to change some of collagen's biochemical or mechanicalproperties to give it new medical applications. Traditionally,scientists have altered collagen by using intense heat or chemicalreactions, techniques that may damage the protein or limit its safe usein humans. Yu's method, however, requires only physical mixing ofcollagen with even smaller molecules called collagen mimetic peptides.

"That's the beauty of this," said Yu, an assistant professor in theDepartment of Materials Science and Engineering. "If you want to attachthese molecules to collagen, you don't have to cook it or use harshchemicals. You just mix them together in a solution."

In lab experiments, Yu and his colleagues have shown that thiskind of molecular marriage does take place. They attached fluorescenttags to the peptides and observed the glow in collagen that had beenmixed with the smaller molecules. Exactly how and why the collagen andthe peptides join is uncertain. But researchers know that collagenmolecules form a distinctive triple-helix in which three long proteinstrands intertwine like rope. Yu speculates that because the smallercollagen mimetic peptides have a propensity to make similartriple-helix structures, they are naturally attracted to collagenmolecules. He believes the peptides make themselves at home within gapsformed by loose collagen strands.

This linkup opens the door to new medical treatments, Yu says, becauseit is easy to attach bioactive agents to the peptides. When thepeptides bind with collagen, these attached agents can dramaticallychange the way collagen behaves in the body. For example, collagennormally attracts cells to close up a wound and form scar tissue. Butthis property is not always desirable; a clot can be dangerous inside ablood vessel or at certain injury sites, where scar tissue caninterfere with the formation of new nerve connections.

Modified collagen can follow a different course. In their recentjournal paper, Yu and his colleagues reported that they had attached achemical, polyethylene glycol, to the peptides, causing collagen torepel cells instead of attracting them. When the researchers addedhuman cells to a lab dish, the cells migrated toward an untreatedcollagen film but avoided the modified collagen sample. This form ofcollagen could stop the formation of blood clots and scar tissue, andscientists may be able to use it to control the shape and organizationof cells and tissue that are grown in a lab, Yu says.

Still other medical uses are possible. A growth factor joined tocollagen could encourage new cells to multiply. An antibiotic attachedto collagen could help a collagen-based bandage fight infections over along period of time. Modified collagen could also release helpfulmedications while serving as a coating for surgical tools and implants.

"With this process," Yu said, "we can make the collagen that's alreadyfound in the human body behave in new ways, including some ways thatare not found in nature. Modified collagen can give us great new toolfor treating injuries and illnesses."

Yu's collaborators on the Journal of the American Chemical Societypaper were Johns Hopkins doctoral students Allen Y. Wang and Xiao Moand former Johns Hopkins biomedical engineering faculty memberChristopher S. Chen, who is now affiliated with the University ofPennsylvania. Yu's research is supported by grants from the NationalScience Foundation and the National Institutes of Health.

Related links:
Michael Yu's Web page: http://engineering.jhu.edu/~jheinen/MATSCI/g/?id=191
Department of Materials Science and Engineering: http://www.jhu.edu/~matsci/