Antimicrobial silver-filled silica nanorattles with low immunotoxicity in dendritic cells.

The progression in the use of orthopedic implants has led to an increase in the absolute number of implant infections, triggering a search for more effective antibacterial coatings. Nanorattles have recently gained interest in biomedical applications such as drug delivery, as encapsulation of the cargo inside the hollow structure provides a physical protection from the surrounding environment. Here, silver-containing silica nanorattles (Ag@SiO2) were evaluated for their antimicrobial potential and for their impact on cells of the immune system. We show that Ag@SiO2 nanorattles exhibited a clear antibacterial effect against Escherichia coli as well as Staphylococcus aureus found in post-operative infections. Immunotoxicological analyses showed that the particles were taken up through an active phagocytic process by dendritic cells of the immune system and did not affect their viability nor induce unwanted immunological effects. Silver-containing silica nanorattles thus fulfill several prerequisites for an antibacterial coating on surgical implants.

Preventing Implant-Associated Infections by Silver Coating.

Implant-associated infections (IAIs) are a dreaded complication mainly caused by biofilm-forming staphylococci. Implant surfaces preventing microbial colonization would be desirable. We examined the preventive effect of a silver-coated titanium-aluminum-niobium (TiAlNb) alloy. The surface elicited a strong, inoculum-dependent activity againstStaphylococcus epidermidisandStaphylococcus aureusin an agar inhibition assay. Gamma sterilization and alcohol disinfection did not alter the effect. In a tissue cage mouse model, silver coating of TiAlNb cages prevented perioperative infections in an inoculum-dependent manner and led to a 100% prevention rate after challenge with 2 × 10(6)CFU ofS. epidermidisper cage. InS. aureusinfections, silver coating had only limited effect. Similarly, daptomycin or vancomycin prophylaxis alone did not preventS. aureusinfections. However, silver coating combined with daptomycin or vancomycin prophylaxis thwarted methicillin-resistantS. aureusinfections at a prevention rate of 100% or 33%, respectively. Moreover, silver release from the surface was independent of infection and occurred rapidly after implantation. On day 2, a peak of 82 µg Ag/ml was reached in the cage fluid, corresponding to almost 6× the MIC of the staphylococci. Cytotoxicity toward leukocytes in the cage was low and temporary. Surrounding tissue did not reveal histological signs of silver toxicity.In vitro, no emergence of silver resistance was observed in several clinical strains of staphylococci upon serial subinhibitory silver exposures. In conclusion, our data demonstrate that silver-coated TiAlNb is potent for prevention of IAIs and thus can be considered for clinical application.

Silver coordination polymers for prevention of implant infection: thiol interaction, impact on respiratory chain enzymes, and hydroxyl radical induction.

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.

Trithiocarbonate-Functionalized PNiPAAm-Based Nanocomposites for Antimicrobial Properties.

In this study, four trithiocarbonate-functionalized PNiPAAms with different molecular weights were synthesized and used as a matrix to form composites with silver nanoparticles. Nanocomposites with several polymer-to-silver ratios P:Ag⁺ were prepared in order to evaluate the influence of silver loading. UV studies showed a thermoresponsive behavior of the nanocomposites with a thermo-reversibility according to cooling-heating cycles. Release kinetics demonstrated that the release of silver ions is mainly influenced by the size of the silver nanoparticles (AgNPs), which themselves depend on the polymer length. Antimicrobial tests against E. coli and S. aureus showed that some of the nanocomposites are antimicrobial and even full killing could be induced.

Synthesis of New Polyether Ether Ketone Derivatives with Silver Binding Site and Coordination Compounds of Their Monomers with Different Silver Salts.

Polyether ether ketone (PEEK) is a well-known polymer used for implants and devices, especially spinal ones. To overcome the biomaterial related infection risks, 4-4'-difluorobenzophenone, the famous PEEK monomer, was modified in order to introduce binding sites for silver ions, which are well known for their antimicrobial activity. The complexation of these new monomers with different silver salts was studied. Crystal structures of different intermediates were obtained with a linear coordination between two pyridine groups and the silver ions in all cases. The mechanical and thermal properties of different new polymers were characterized. The synthesized PEEKN5 polymers showed similar properties than the PEEK ones whereas the PEEKN7 polymers showed similar thermal properties but the mechanical properties are not as good as the ones of PEEK. To improve these properties, these polymers were complexed with silver nitrate in order to "cross-link" with silver ions. The presence of ionic silver in the polymer was then confirmed by thermogravimetric analysis (TGA) and X-ray powder diffraction (XRPD). Finally, a silver-based antimicrobial compound was successfully coated on the surface of PEEKN5.

New antimicrobial and biocompatible implant coating with synergic silver-vancomycin conjugate action.

Materials foreign to the body are used ever more frequently, as increasing numbers of patients require implants. As a consequence, the numbers of implant-related infections have grown as well, and with increasing resistance. Treatments often fail; thus, new antibacterial coating strategies are being developed by scientists to avoid, or at least strongly reduce, bacterial adhesion to implant surfaces. In this study, we focused on producing a self-protective coating combining silver(I) ions and a vancomycin-derived molecule, intelligent pyridinate vancomycin (IPV), with a synergetic and effective action against bacteria. These Ag(I) -IPV conjugate-coated surfaces are well characterized and exhibit strong bactericidal activity in vitro against Staphylococci strains. Furthermore, the released quantities of both drugs from the coated surfaces do not affect their biocompatibility and soft tissue integration. These newly developed Ag(I) -IPV conjugate coatings thus represent a possible and efficient protection method against bacterial adhesion and biofilm formation during and after implant surgery.

Rings, chains and helices: new antimicrobial silver coordination compounds with (iso-)nicotinic acid derivatives.

Complexes with silver ions have great potential for applications in medicine. Appropriate bidentate ligands, binding to silver ions, are able to generate coordination polymers as well as molecular entities as a function of ligand flexibility, conformation and length. Here we present the continuation of our previous studies in this field with ligands based on oligomers of polyethylene glycol, functionalized at both ends with either nicotinic or isonicotinic acid. The structures of three ligands and nine new coordination compounds are presented. A large variety of structures are obtained as a function of counterion, solvent and ligand-to-metal ratio, such as isolated rings, offset stacked rings, parallel chains and entangled chains, and their antimicrobial properties as well as biocompatibility are assessed.

In vitro Biocompatibility of New Silver(I) Coordination Compound Coated-Surfaces for Dental Implant Applications.

Biofilm formation on implant materials causes a common problem: resistance to aggressive pharmacological agents as well as host defenses. Therefore, to reduce bacterial adhesion to implant surfaces we propose to use silver(I) coordination networks as it is known that silver is the most powerful antimicrobial inorganic agent. As a model surface, self-assembled monolayers (SAMs) on gold Au(111) was used to permit permanent attachment of our silver(I) coordination networks. The surface coatings showed typical nano-structured surfaces with a good biocompatibility for soft-tissue integration with fibroblast cells.