May 15 2005
By mimicking an adhesive protein secreted by mussels and a polymer that repels cells and proteins, researchers at Northwestern University have designed a versatile new two-sided coating that could breathe life into medical implants.
Currently the longevity of certain medical implants suffers because bacteria, cells and proteins in the body gradually accumulate on the devices (known as fouling), compromising their performance and threatening patients with infections. Unfortunately, the polymers that studies have shown to be effective at antifouling do not last long in-vivo, falling prey to chemical degradation or to the body's enzymes.
In contrast, the molecular compound developed at Northwestern, which sticks securely to a surface and prevents cell and protein buildup, works for a long period of time. In laboratory studies, the new coating provided effective fouling resistance for more than five months, which Phillip B. Messersmith, associate professor of biomedical engineering in the McCormick School of Engineering and Applied Science and lead investigator in the study, believes to be the longest successful in-vitro antifouling demonstration.
The findings are published onlin by the Journal of the American Chemical Society, a peer-reviewed publication of the American Chemical Society.
While the coating has not been tested in humans, it holds promise for use on a variety of medical implants including urinary catheters, cardiac stents, biosensors and dental implants and devices. The coating also could be used to prevent the biofouling of water processing equipment, ship hulls and other manmade structures in the marine environment.
Looking for a solution to the longevity problem in existing coatings, Messersmith teamed up with Annelise Barron, associate professor of chemical and biological engineering and an author on the paper. Barron is an expert at creating peptoids -- synthetic molecules that are closely related to the natural proteins or peptides they mimic but don't degrade in the body.
Messersmith and Barron wanted to use this durability of peptoids to the antifouling coating's advantage. They proceeded to intelligently design a new polymer made up of two parts, both playing a key role: a short peptide that is the synthetic version of the sticky dihydroxyphenylalanine (DOPA) molecule that gives mussels their adhesive or anchoring strength and a longer peptoid polymer resembling the structure of polyethylene glycol (PEG), a widely studied antifouling polymer.
"We had a rich chemistry available to us when designing this polymer," said Messersmith. "The chemical characteristics of the antifouling component are similar to polyethylene glycol but it lasts longer because it is a peptoid and enzyme resistant. Plus, the structure of the polymer's backbone, which is based on a natural peptide, should make it very biocompatible and prevent evoking an immune response in the body."
The researchers tested their coating on titanium dioxide (a material common in medical implants) in environments that simulated physiologic conditions with fresh serum and cells. The coating anchored itself firmly to the surface and demonstrated excellent resistance to proteins and cells during the five-month experiment. For the same reason the coating is cell and protein resistant, it should also prove to be bacteria resistant, Messersmith said.