Photo by Will Owens

Ross and Charlotte Johnson Family Dissertation Fellow Brian Nablo utilized his microbiology background in his chemistry research to fight bacterial infections on medical implants.

Brian Nablo works toward making safer medical implants

From artificial joints to IV catheters, medical implants play a huge role in modern medical practices. Nevertheless, the potential for bacterial infection presents a challenge for doctors and often makes these devices harmful to patients. Armed with a background in microbiology, Brian Nablo came to Carolina in the fall of 1999 for a doctoral degree in chemistry and the chance to tackle this problem. Working with Professor Mark H. Schoenfisch in the Department of Chemistry, Nablo and his research team have harnessed the power of nitric oxide to fight the development of biofilms on medical implants and reduce the potential for infection. Now in his final year, Nablo is focusing on completing his dissertation thanks to the Ross and Charlotte Johnson Family Dissertation Fellowship, part of the Royster Society of Fellows. In a conversation with The Fountain’s Alexandra Obregon, he offers insight into his research and its prospective benefits in the field of implant medicine.

The Fountain: You’re working with medical implants to make them less prone to bacterial infection. How often are these implants used on patients?

Brian Nablo (BN): Statistics change almost every year. More than half a million to a million people worldwide receive orthopedic implants. Nearly every person who is hospitalized these days, about 75 to 90 percent, receives a catheter. If you go into a hospital, more than likely you’re going to receive some sort of implant, especially if you’re seriously injured. On top of that, if you receive an infection from
a hospital situation, about 50 percent of the time it’s due to the implant. So it’s very important these days to address this problem.

Fountain: Are any of these infections serious or fatal?

BN: In most cases they can be detected right away. You can get an infection around a catheter, but doctors can just remove that implant. If we’re talking about orthopedic implants, like joint, knee or hip replacements, about 5 percent of those are infected after the surgical procedure. Usually, there’s chronic pain associated with that so you can detect it. Not many are fatal, but they cause a lot of other
problems such as systemic infections that can cause fevers when the infection spreads to other parts of the body. In the worst case scenario with these permanent implants, the implant becomes the source of the infection. The only method of treatment is to remove the implant and possibly go through another
implantation, which is a horrible ordeal for the patient and the doctor.

Fountain: How did you get started on the project? Did the different kinds of implants dictate the way you approached the research?

BN: My adviser (Professor Mark H. Schoenfisch) got here the same year I did, and he was working with nitric oxide. He was looking at the biocompatibility of the implant with the human body. With my background in microbiology, I knew nitric oxide is also used in the immune system, where
macrophages, your white blood cells, use nitric oxide to kill bacteria. It’s just a normal immune process, so I thought, “Why don’t we just try this with bacteria, too?” Our group then developed an excellent system in which we use sol-gel, which is basically liquid glass. The liquid precursors are laid down on the surface to make a glass coating. Donor molecules inside the coating can release nitric oxide over time. We knew that approaching the issue from an implant pathology perspective would be a problem. But stepping back, we figured this liquid glass design potentially could modify almost anything and address all implants. The science behind it really sparked the interest.

Fountain: What types of bacteria are you working with?

BN: We really tried to target the species that were the most important. We wanted to work with the main three strains. The first two are Staphylococcus aureus, which everyone hears about since staph infections are so common, and Staphylococcus epidermidis. Those two are the most important because they dwell on your skin. If you get an implant infection, most likely it’s staph, because we carry them
around everywhere. Our main workhorse is Pseudomonas aeruginosa. Although less medically
important to implants, we push Pseudomonas because of the issue of biofilms, which can be analogous to that grimy film that builds up in your sink over time if you don’t clean it very often. Imagine those same films on implants in your body. Microorganisms can make these protective layers so they can
stick to surfaces and be protected from the environment. This is what makes biofilms so dangerous
for medical implants, because they are protected from the immune system and antibiotics. Pseudomonas aeruginosa is one of the most characterized biofilm-forming species.

Fountain: Is there a period during which an infection is more likely to occur?

BN: That depends on the type of implant, and we’re approaching the issue from both ends. If the implant is completely inside the body and closed off from the environment, usually only about the first few weeks are important. On the other hand, in orthopedics you have some implants that come out of the body and use external fixators. An example would be neck braces, which have screws coming out of the skin. External fixation is far better than an internal bone screw because the outside brace hold stabilizes the screw to quicken healing. Doctors want to use these external fixators for bone bracing, but a problem arises at the skin site. The screw breaches the skin and causes a continuous wound. So, all those bacteria resident on your skin start to creep into that hole slowly over time, causing a continuous problem for the life of the implant. Anything with a skin breach has a potential for infection. With that type of window, we’re looking at possible bacterial infection throughout the lifetime of the implant, which for most transdermal implants is probably two to four weeks, maybe even two to three months. We’re trying to target that area with a very long-term nitric oxide. With the internal implant we’re looking at a short dose for a couple of weeks. Regardless of lifetime, we envision the nitric oxide released from these implant coatings repelling the invasive bacteria. This would allow for the immune system of the host to take care of microbes more effectively.

Fountain: How have you been testing it so far?

BN: We look for adhesion within the first hour. We’re just going from the assumption that if there aren’t as many bacteria adhering to the surface, you’re less likely to get a biofilm. We throw this coated surface in a solution of bacteria, let it stir for about a half-hour and then pull it out and see if the adhesion occurred or not. There’s a dramatic difference. With the orthopedic project we have just bare steel, bare steel with our sol-gel (the glassy coating), and steel with the sol-gel that releases nitric oxide. The bare steel and the sol gel surface look pretty much the same. But, when the nitric oxide release is added, a dramatic drop in the adhesion of these bacteria is seen.

Fountain: With bacteria, there is always a concern that treatments doctors use to fight infections lead to bacterial strains that are more resistant to the medicine. Is there a risk of that happening with nitric oxide?

BN: The nice thing about nitric oxide is that it’s a chemical, a gas molecule. There is no way to inactivate it in the way antibiotics are inactivated. I envision nitric oxide as an indicator of unwelcoming conditions. This is like going to a place with a lot of trash. You think, “This is a dirty and stinky place. I don’t want to be here.” If there’s a huge amount of nitric oxide around, bacteria think, “There’s a lot of waste products and some harmful stuff around. I don’t want to be on this surface.” If that’s the premise, building resistance to nitric oxide would be kind of difficult from what we understand now. Of course, that can always turn around. Bacteria are great at evolving.

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