Preventing bacterial infections in implants

A silver nanoparticle container with a cerium shell and titanium dioxide coating (K. Fromm/UniFR)Nanocontainers developed by NCCR Bio-Inspired Materials researchers could provide a controlled solution using silver compounds to fight infections related to biomedical implants.

As life expectancy grows, the use of biomedical implants has become more common to fix or replace those parts of the body suffering from wear and tear. Surgeons regularly replace hips or knees that no function properly due to overuse or age.

While this usually results in an improvement of quality of life for the patient, successful implantation is often hindered by bacterial infections. For example, when a biofilm containing bacteria becomes embedded on the surface of an implant, the solution is normally to completely remove the implant and replace it with a new one.

The result is unnecessary pain for the patient, additional medical costs and no guarantee it will not happen again. Heightened bacterial resistance to antibiotics means that new approaches are required to deal with these infections.

Researchers have looked to silver to deal with the problem. It has been used for thousands of years to treat wounds, breaking down the chemical bonds that bacteria require to multiply. Too much though can be toxic for tissues surrounding the area where it is applied, but it has many advantages too.

“Silver has been long tested on humans - think of silver cutlery for example,” says NCCR principal investigator Katharina Fromm. “Silver does also not have a role in the human body, so it will not interact with specific body functions.”

Silver-based drugs are efficient against a wide variety of bacteria. Many of them are commercially available, such as silver nitrate solutions to prevent and cure eye infections, and silver sulfadiazine in wound dressings to increase repair and prevent infections, especially in the case of burns.

However, some the more recent silver-based drugs work extremely fast, increasing the risk of damage to surrounding tissue and only having a short-term impact. Prolonged exposure to high silver concentrations can also lead to argyria, a non-fatal condition leading to a grayish-blue discoloration of the skin.

For implants that remain within the human body for many years, the release of silver therefore has to be controlled to avoid any undesired effects. To overcome these issues, NCCR researchers have looked at using nanocontainers to transport and slowly release silver anti-bacterial compounds.

“You use less of the drug, it is protected from degradation and delivered on demand,” adds Fromm, a professor of chemistry at the University of Fribourg. “It avoids flooding the whole body with drugs, targeting the site where it is needed the most at the appropriate time.”  

The scientists developed silver-containing nanocapsules made of ceria – an oxidated form of the rare earth element cerium – with an additional coating of titanium dioxide, a compound used notably in the food industry and in sunscreen.  Metal-based implants, such as hip implants, are normally made of titanium or titanium alloys whose surface oxidizes in contact with aqueous environments, making them a potential candidate for the development of antimicrobial implant surfaces.

Testing showed that the nanocontainers would release almost none of their payload in a pH-neutral environment over a three-month period, but are activated when that environment becomes acid, similar to what happens when bacteria are present. The containers were found to be particularly effective against E. coli, common bacteria found in the environment, as well as in foods and the intestines of people and animals.

These results suggest these nanocontainers could be used for the prevention of implant-associated infections. However it should not be considered a ‘silver’ bullet yet.

“I believe that combinations of several antimicrobial compounds will have to be used,” says Fromm. “You will have to hit the bacteria at several places at the same time.”

More research is now required to ensure the method is less harmful towards human cells, with the long-term goal of developing a commercially viable product.    

Contact:

Prof. Katharina Fromm

Department of Chemistry

University of Fribourg

Chemin du Musée 9

1700 Fribourg

Switzerland

+41 26 300 8732

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Journal article:
Gagnon, J.; Clift, M. J. D.; Vanhecke, D.; Widnersson, I. E.; Abram, S.-L.; Petri-Fink, A.; Caruso, R. A.; Rothen-Rutishauser, B.; Fromm, K. M. Synthesis, Characterization, Antibacterial Activity and Cytotoxicity of Hollow TiO 2 -Coated CeO 2 Nanocontainers Encapsulating Silver Nanoparticles for Controlled Silver Release. J. Mater. Chem. B 2016, 4 (6), 1166–1174.

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