According to folklore, silver bullets kill werewolves, but in reality, researchers have been looking to harness this metal against bacteria. Scientists at the University of British Columbia have now developed a long-acting silver-ion releasing coating for implanted medical devices that, when tested in experiments in rats, both prevented bacteria from adhering to the implant, and also killed the microorganisms.
Dirk Lange, PhD, Jayachandran Kizhakkedathu, PhD, and colleagues described the development of the new silver-based film-forming antibacterial engineered (SAFE) coating, in the journal ACS Sciences. They reported that the coating, which could be applied via single-step dipping, spraying, or solution-skinning processes, was nontoxic, and enabled sustained, long-term silver release from different types of surfaces and medical devices, which stopped bacteria from adhering to these materials over 30 days. In their paper titled, “Durable Surfaces from Film-Forming Silver Assemblies for Long-Term Zero Bacterial Adhesion without Toxicity,” they concluded, “The coating showed broad-spectrum antibiofilm activity, was able to prevent infection in a rat infection model, and was found to be highly biocompatible in vitro and in vivo without silver toxicity. The current coating is anticipated to have broad application for diverse medical devices and implants to prevent implant-/device-associated infections.”
Implanted medical devices, such as tubes used to drain wounds or the bladder, or to deliver medication directly into the blood, can quickly become colonized by bacteria, creating a risk for dangerous infections. “Given that the surface of commercially available indwelling medical devices is highly prone to bacterial colonization and biofilm formation, their implantation into the body is disposed to a high risk of infection,” the authors wrote.
Researchers have been working to develop bacteria-repelling coatings, including those containing silver, which is known to kill microbes. “One of the extensively used antimicrobial agents to generate release-killing coatings is silver, which possesses a strong bactericidal potency, has improved protection against microbial resistance, and can be prepared from economical precursors,” the team explained. However, efforts to date using a variety of potential approaches, have faced numerous challenges. “The long-term prevention of biofilm formation on the surface of indwelling medical devices remains a challenge,” Lange and colleagues pointed out. “Current antibiofilm coating technologies, including antifouling coatings, contact-killing surfaces, and antibiotic/bactericide releasing coatings, have failed to endow long-term prevention of bacterial attachment and biofilm formation (>7 days).”
Silver can also be toxic to human cells, and it’s difficult to make a coating that continually releases small amounts of the metal over long periods, for example. “Silver has been reutilized in recent years for combating biofilm formation due to its indisputable bactericidal potency,” the team continued, “however, the toxicity, low stability, and short-term activity of the current silver coatings have limited their use.”
Lange, Kizhakkedathu, and colleageus wanted to identify a silver-containing formula that could overcome these and other difficulties. To develop a simple-to-use coating, the team screened many sets of ingredients that they could apply to a surface in a single step. The formula that worked the best included silver nitrate, dopamine, and two hydrophilic polymers. This SAFE coating formed stable, silver-containing assemblies, which gradually released silver ions in lab tests. “The coating composition was identified through a library screening approach with four different components providing surface binding, stability, antiadhesion, and antimicrobial properties,” they explained. “Detailed surface analyses provide mechanistic information regarding the formation of nanostructures, the self-assembly process, film formation, and the coating stabilization.
When exposed over 28 days to eight of the most common species of bacteria that cause serious infections, the new coating recipe effectively kept the microbes at bay. It did so in a unique way: by both repelling the bacteria from the surface and then killing them with silver ions. “… the SAFE coating was found to completely inhibit bacterial biomass deposition by both Gram-negative (E. coli) and Gram-positive (S. saprophyticus) species in comparison to control samples, demonstrating its excellent long-term activity,” the investigators reported.
For in vivo tests, the team applied the SAFE coating to the surface of titanium implants, which were then placed under the skin of rats. After a week, the researchers found that implants with the coating had dramatically fewer bacteria than those without it, and compared with those to which had been applied a “control-Ag” coating. In addition, there were no signs of toxicity to the rats’ tissues. “We demonstrated that the sustained release of silver ions at therapeutic doses in combination with the excellent antiadhesion property of the coating resulted in zero bacterial adhesion and colonization for several weeks … The SAFE coating significantly reduced the number of bacteria on the implant in comparison to the uncoated and “control Ag”-coated samples. Except for one implant, all of the SAFE-coated implants showed zero bacterial counts on the surface.”
The SAFE coating also appeared tough, showing little wear and tear after being rubbed and sterilized using harsh conditions. This combination of attributes is likely to make the coating useful in many types of medical devices and implants to prevent bacterial infection over the long term, the researchers suggest. The coating could also be applied using different, one-stage dipping, spraying, and solution-skinning processes. “Collectively, the data showed that diverse materials or medical devices can be effectively coated with the SAFE composition via different coating methods, demonstrating the versatility of the SAFE-coating process,” the scientists stated. The different methods of application did result in different thicknesses of coating, which the scientists acknowledged will need further evaluation to see if this impacts long-term activity.
Nevertheless, the researchers concluded, “In this work, we developed SAFE assemblies that form silver coatings with long-term null bacterial adhesion (>30 days) without silver toxicity, demonstrated both in vitro and in vivo. SAFE assemblies resulted in a lubricious surface coating with sustained long-term silver release, excellent surface coverage, and high mechanical durability on diverse surfaces and medical devices via a highly adaptable one-step dipping, spraying, or ‘solution-skinning’ coating process.”