Medical implants like catheters and pacemakers can be a hotspot for bacteria, which grow in hard-to-treat films on the surface of such devices. Scientists and engineers are taking different approaches to changing the surface of implants so bacteria cannot take hold. Some groups are developing polymer films with structures that prevent bacterial growth, while others are developing coatings that slowly release antibiotic compounds over time.
Researchers from Clemson University in South Carolina and the University of Southern Mississippi have described how a layer of bacteria-killing viruses could help prevent bacterial infections. In a study published in Biomacromolecules, 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 can then go on to 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 can both be killed by tethered bacteriophages. The team writes that their method could work with almost any surface, and add that beyond fighting infections, their idea could also 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 MIT 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% of knee and hip replacement surgeries result in infection; the number rises to 3-5% for second surgeries. “It’s a low rate, but if you are the one out of one hundred who gets an infection, the complications are catastrophic,” says 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 are also enormously expensive. A joint replacement costs about US$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, says 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 have already 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 mustn’t interfere with joint articulation. Researchers led by Paula Hammond, professor of chemical engineering at MIT, 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%, rather than the more usual 4%. 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.
A new study by MIT researchers demonstrates that bacteria adhere poorly to soft surfaces and stick to firm ones. The findings challenge conventional wisdom and could hold the key to creating better antibacterial coatings. The researchers have also created soft polymer films that might serve as antibacterial coatings for medical devices and other objects on which harmful bacteria congregate. Preventing bacteria from adhering to medical devices is critical to combating biofilms, a major cause of hospital-acquired infections. Biofilms are sticky, antibiotic-resistant bacterial colonies that commonly form on catheters, the hulls of ships, water-treatment pipes, and even inside the lungs and inner ear. There is no foolproof method for preventing biofilm formation. Once they are established, biofilms are difficult to eradicate because traditional antibiotics cannot get through the films’ sticky secretions to kill the individual bacteria. Biofilms are an area of intense research in microbiology, but until the recent MIT study, no one had tested whether changing the mechanical stiffness of a surface would affect their formation. Krystyn Van Vliet and Michael Rubner, both professors of materials science and engineering at MIT, investigated the behavior of E. coli and a strain of Staphylococcus responsible for many hospital infections. The bacteria were incubated on polymer films whose stiffness was controlled with great precision. Van Vliet and Rubner found that these two very different bacteria shared a sensitivity to surface mechanics. The number of bacteria that will adhere to a stiff surface is orders of magnitude greater than that of the bacteria that will stick to a soft one. And the soft films, created by dipping an object into water-based solutions of biocompatible polymers, “can coat anything,” says Van Vliet.