New Research Delves Into Polymer Coatings to Reduce Implant Infections

According to a new study published in Biomacromolecules, researchers from Clemson University in South Carolina and the University of Southern Mississippi have found that a layer of bacteria-killing viruses could help prevent bacterial infections that develop on the films of various surgical implants.
The investigators describe a new method for attaching bacteria-busting viruses, also known as bacteriophages, to plastic and Teflon-type materials. When a bacterium gets too close to these enemy-coated surfaces, a tethered bacteriophage can grab on and inject its genetic material into the bacterial cell where it is copied and turned into many more bacteriophage. Eventually, these virus copies burst open the bacteria, killing it. Each newly freed bacteriophage then can infect more bacteria (the authors note that this “amplification effect” could make it hard to control the population size of the bacteria killers). The researchers show that E. coli and the species of bacteria that causes staph infections both can be killed by tethered bacteriophages. The team writes that their method could work with almost any surface, and contend that beyond fighting infections, their idea also could be used as a “technological platform for the development of bacteria sensing and detecting devices.”

Infections resulting from joint-replacement surgeries are costly and potentially deadly. Researchers at the Massachusetts Institute of Technology (MIT), led by Paula Hammond, professor of chemical engineering, are developing coatings for medical implants that can be loaded with multiple drugs, including antibiotics that are released over time. The process involves layering antibiotic films, which are released over the short term, onto a permanently antibacterial polymer designed to prevent infection over the long term. About 1 percent of knee and hip replacement surgeries result in infection; the number rises to 3-5 percent for second surgeries.

“It’s a low rate, but if you are the one out of 100 who gets an infection, the complications are catastrophic,” said Lloyd Miller, assistant professor of orthopedic surgery at the University of California, Los Angeles. All the infected tissue and hardware must be surgically removed and replaced with an antibiotic block; the patient cannot walk for six to eight weeks while being treated with intravenous antibiotics to eliminate all traces of infection; and then a revision surgery is done.

Complications due to infection also are expensive. A joint replacement costs about $30,000 in the United States, but dealing with infections can raise the tab nearly five-fold. Most infections happen when bacteria enter the body with an implant. But artificial joints can become infected years later when bacteria are introduced into the bloodstream during dental work, colonoscopies, and other procedures, said Miller, who is not affiliated with the MIT group. Orthopedic coatings that have permanent antibacterial properties in addition to a transient coating of antibiotics could keep patients protected. Although antibiotic coatings for many other medical devices already have been developed, coatings for joints pose particular challenges. Unlike stents and other devices that are static, joints have to be able to move. So the coating can’t be too thick, and it must not interfere with joint articulation.

Hammond and her team are using a polymer-coating technique called layer-by-layer assembly to load large concentrations of drugs into implant coatings without making them too thick. Hammond’s group builds up these films by dipping an implant alternately in solutions of negatively and positively charged molecules such as polymers and drugs. The difference in surface charge holds each layer tightly to those above and below it. This process leads to very thin layers of materials, on the order of tens of nanometers thick. The drugs will be released when the polymers biodegrade inside the body.

Alternating layers of drugs with layers of a biodegradable polymer, rather than mixing polymer and drug and slathering the mixture on an implant, results in a thinner coating that contains a higher proportion of the drug—as much as 50 percent, rather than the customary 4 percent. And these coatings can be produced at low temperatures and in water, rather than in the harsh conditions usually required for polymer processing. This means they are compatible with a broader range of delicate molecules including protein drugs and therapeutic RNA. Patients who have a poor vascular system that can compromise bone growth, including diabetics and heavy smokers, might benefit from coatings that release drugs to stimulate bone formation or blood-vessel growth, in addition to antibiotics.