Antimicrobial Coating for Implants Shown to Prevent Infections
Although still only applicable in animal studies, an antibiotic coating that can be applied to orthopaedic implants minutes before surgery to potentially eliminate the chance of infection developing around the implant could have game-changing implications for joint replacement patients.
In early trials in mice, the coating was shown to prevent infections even when the mice that did not receive antibiotic infusions. After 20 days, the coating did not reduce the bone’s ability to fuse with the implant and was completely absorbed by the body.
The study findings, from a team of biomedical engineers and surgeons at Duke University and UCLA, were published online in the journal Nature Communications.
Challenges to Preventing Infections
Infections occur in 1% of primary total joint arthroplasty (TJA) patients and up to 7% of revision TJA patients, and they can be challenging to treat. Often, the only recourse is removal of the original implant, which is usually the best of what are only bad options.
To reduce the risk of infection, surgeons may use an antibiotic powder when closing the surgical wound or add antibiotics to bone cement. However, neither tactic has been proven to be clinically effective in preventing all initial or repeat infections.
Manufacturers could add antibiotic properties to their implants, but this would greatly reduce the shelf life of the implant. It would also require a long and complicated process of review and approval by regulatory authorities – for example, the Food and Drug Administration in the US – given that antibiotic-impregnated implants would be in a new device classification.
A Solution that Just “Clicks”
The antibiotic coating sidesteps these challenges.
“We’ve shown that a point-of-care, antibiotic-releasing coating protects implants from bacterial challenge, and can be quickly and safely applied in the operating room without the need to modify existing implants,” said Christopher Hart, MD, a research resident in the UCLA Orthopaedic Surgery residency program, who helped conduct the experiments.
The new antimicrobial coating consists of 2 polymers, 1 that repels water and 1 that mixes well with water. Both are combined in a solution with an antibiotic of the physician’s choosing and then applied directly to the implant by dipping, painting, or spraying (Figure 1). When exposed to a bright ultraviolet light, the 2 polymers couple together and self-assemble into a grid-like structure that traps the antibiotics.
Figure 1. The antibiotic rifampin mixed with a self-assembling solution of polymers is coated onto human intramedullary hip implants. Photo courtesy of Segura Laboratory and Bernthal Laboratory.
The reaction is an example of “click chemistry,” which is a general way of describing reactions that happen quickly at room temperature, produce only a single reaction product, have an extremely high yield, and occur within a single container.
“This study is a great example of the power of click chemistry in biomedical applications,” said Weixian Xi, PhD, now a senior scientist at Illumina, who was a postdoctoral researcher at UCLA during the study.
“This ‘smart’ and ‘clickable’ polymeric coating enables protections of implants from bacterial infection and makes a personalized approach possible.”
Almost Any Antibiotic Can Be Used
The antibiotic coating was developed in the lab of Tatiana Segura, PhD, professor of biomedical engineering at Duke.
“Our coating can be personalizable because it can use almost any antibiotic,” Dr. Segura said. “The antibiotic can be chosen by the physician based on where in the body the device is being implanted and [which] pathogens are common in whatever part of the world the surgery is taking place.”
The click chemistry polymer grid also has an affinity for metal. Tests involving various types of implants showed that the coating was very difficult to rub off during surgical procedures. Once inside the body, however, the conditions cause the polymer to degrade, slowly releasing the antibiotics over the course of 2 to 3 weeks.
Continuing Research with Animal Models
For the study, researchers rigorously tested the coating with 2 mouse models: a post-knee replacement infection model and a post-spinal surgery infection model. After 20 days, the researchers found that none of the implants treated with the antibiotic coating grew infectious organisms. Nor did the antibiotic coating in inhibit the bone’s growth into the implant. This time period, the researchers say, is long enough to prevent the vast majority of infections from occurring.
The researchers have not yet tested their coating on larger animals. Since larger animals—such as humans—have larger bones and need larger implants, there is much more surface area to protect against bacterial infections. But the researchers are confident that their invention is up to the task and plan to pursue the steps needed to commercialize the product.
“We believe this transdisciplinary work represents the future of surgical implants, providing a point of application coating that transforms the implant from a hotspot for infection into a ‘smart’ antimicrobial therapeutic,” said Nicholas M. Bernthal, MD, the Interim Chair and Executive Medical director at the David Geffen School of Medicine at UCLA.
“You only need to treat a single patient with an infected implant to realize how transformational this could be for patient care – saving both life and limbs for many.”
Xi W, Hegde V, Zoller SD, et al. Point-of-care antimicrobial coating protects orthopaedic implants from bacterial challenge. Nat Commun. 2021 Sep 16;12(1):5473. doi: 10.1038/s41467-021-25383-z.