Prosthetic joint replacements are used increasingly to alleviate pain and improve mobility of the progressively older and more obese population. Implant infection occurs in about 5% of patients and entails significant morbidity and high social costs. It is most often caused by staphylococci, which are introduced perioperatively. They are a source of prolonged seeding and difficult to treat due to antibiotic resistance; therefore, infection prevention by prosthesis coating with nonantibiotic-type anti-infective substances is indicated. A renewed interest in topically used silver has fostered development of silver nanoparticles, which, however, present a potential health hazard. Here we present new silver coordination polymer networks with tailored physical and chemical properties as nanostructured coatings on metallic implant substrates. These compounds exhibited strong biofilm sugar-independent bactericidal activity on in vitro-grown biofilms and prevented murine Staphylococcus epidermidis implant infection in vivo with slow release of silver ions and limited transient leukocyte cytotoxicity. Furthermore, we describe the biochemical and molecular mechanisms of silver ion action by gene screening and by targeting cell metabolism of S. epidermidis at different levels. We demonstrate that silver ions inactivate enzymes by binding sulfhydryl (thiol) groups in amino acids and promote the release of iron with subsequent hydroxyl radical formation by an indirect mechanism likely mediated by reactive oxygen species. This is the first report investigating the global metabolic effects of silver in the context of a therapeutic application. We anticipate that the compounds presented here open a new treatment field with a high medical impact.With ageing populations and rising obesity, the number of patients requiring joint replacement or internal fixation devices is steadily increasing. Occurring at a rate of 5%, orthopedic implant infections remain one of the most devastating complications (45). Low-virulence organisms, including Staphylococcus epidermidis, are mostly responsible for perioperative infections of implants (50), when bacteria proliferate and cluster in multilayers known as biofilms (15). This structure allows bacteria to resist antimicrobial agents and immune responses (24).Therefore, early prevention of infection is a major clinical concern. An attractive concept for protection against infection is the entrapment of pharmaceuticals in matrices on and around implant surfaces and their subsequent release by diffusion. With increasing bacterial resistance against antibiotics, silver and its compounds-historically well known for their antimicrobial effect-have come back into the focus of research (9). Silver ions are proposed to react with electron donor groups (N, O, or S atoms), which are present in bacteria as, e.g., amino, imidazole, phosphate, carboxyl, or thiol groups in proteins or in DNA (8). While the interaction with thiol groups seems to play an essential role in bacterial inactivation (27), it is uncl...

Silver coordination polymer chains were deposited on Au(111) as a model surface, as well as on gold alloy and titanium as dental implant and restorative materials. The topography of the surface was analysed on the model substrate and it was found to be a nano-structured crystalline material. In vitro investigations in a flow chamber imitating the oral environment prove the anti-bacterial properties of the silver compound.