Bacterial colonization of implant surfaces is a feared complication in surgery and orthopedics. Due to the increasing number of periprosthetic infections caused by multidrug-resistant microorganisms, new antibacterial coatings for biomaterials must be developed. The excellent antibacterial properties of silver nanoparticles (AgNPs) against multidrug-resistant bacteria, for example, have been repeatedly described. For this reason, we tested a nanosilver-doped polymethylmethacrylate (PMMA) bone cement and a nanosilver-coated titanium alloy regarding their influence on osteoclastogenesis of primary human peripheral blood mononuclear cells. Both implant variants did not inhibit osteoclast differentiation. Excellent cell attachment and unaltered podosomal structures were confirmed. Additionally, no induction of oxidative or endoplasmic reticulum stress could be observed. However, PMMA loaded with gentamicin and nanosilver inhibited preosteoclast fusion and further osteoclastogenesis. The material also led to decreased clathrin-dependent endocytosis as well as decreased levels of endoplasmic reticulum stress. Therefore, biomaterial functionalization with AgNPs did not disturb osteoclastogenesis, while addition of gentamicin reduced the cytocompatibility of nanosilver-doped materials towards human osteoclasts.

1.
Albers, C.E., W. Hofstetter, K.A. Siebenrock, R. Landmann, F.M. Klenke (2013) In vitro cytotoxicity of silver nanoparticles on osteoblasts and osteoclasts at antibacterial concentrations. Nanotoxicology 7: 30-36.
2.
Alt, V., T. Bechert, P. Steinrücke, M. Wagener, P. Seidel, E. Dingeldein, E. Domann, R. Schnettler (2004) An in vitro assessment of the antibacterial properties and cytotoxicity of nanoparticulate silver bone cement. Biomaterials 25: 4383-4391.
3.
Arora, M., E.K.S. Chan, S. Gupta, A.D. Diwan (2013) Polymethylmethacrylate bone cements and additives: a review of the literature. World J Orthop 4: 67-74.
4.
Berbari, E.F., A.D. Hanssen, M.C. Duffy, J.M. Steckelberg, D.M. Ilstrup, W.S. Harmsen, D.R. Osmon (1998) Risk factors for prosthetic joint infection: case-control study. Clin Infect Dis 27: 1247-1254.
5.
Campoccia, D., L. Montanaro, C.R. Arciola (2006) The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials 27: 2331-2339.
6.
Carlson, C., S.M. Hussain, A.M. Schrand, L.K. Braydich-Stolle, K.L. Hess, R.L. Jones, J.J. Schlager (2008) Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J Phys Chem B 112: 13608-13619.
7.
Chang, Y., C.L. Tai, P.H. Hsieh, S.W.N. Ueng (2013) Gentamicin in bone cement: a potentially more effective prophylactic measure of infection in joint arthroplasty. Bone Joint Res 2: 220-226.
8.
Choi, O., K.K. Deng, N.J. Kim, L. Ross, R.Y. Surampalli, Z. Hu (2008) The inhibitory effects of silver nanoparticles, silver ions, and silver chloride colloids on microbial growth. Water Res 42: 3066-3074.
9.
Corisdeo, S., M. Gyda, M. Zaidi, B.S. Moonga, B.R. Troen (2001) New insights into the regulation of cathepsin K gene expression by osteoprotegerin ligand. Biochem Biophys Res Commun 285: 335-339.
10.
Galvez-Lopez, R., A. Pena-Monje, R. Antelo-Lorenzo, J. Guardia-Olmedo, J. Moliz, J. Hernández-Quero, J. Parra-Ruiz (2014) Elution kinetics, antimicrobial activity, and mechanical properties of 11 different antibiotic loaded acrylic bone cement. Diagn Microbiol Infect Dis 78: 70-74.
11.
Gasquères, C., G. Schneider, R. Nusko, G. Maier, E. Dingeldein, A. Eliezer (2012) Innovative antibacterial coating by anodic spark deposition. Surf Coat Technol 206: 3410-3414.
12.
Haase, A., S. Rott, A. Mantion, P. Graf, J. Plendl, A.F. Thunemann, W.P. Meier, A. Taubert, A. Luch, G. Reiser (2012) Effects of silver nanoparticles on primary mixed neural cell cultures: uptake, oxidative stress and acute calcium responses. Toxicol Sci 126: 457-468.
13.
Jafari, S.M., C. Coyle, S.M. Mortazavi, P.F. Sharkey, J. Parvizi (2010) Revision hip arthroplasty: infection is the most common cause of failure. Clin Orthop Relat Res 468: 2046-2051.
14.
Jurdic, P., F. Saltel, A. Chabadel, O. Destaing (2006) Podosome and sealing zone: specificity of the osteoclast model. Eur J Cell Biol 85: 195-202.
15.
Kalishwaralal, K., S. BarathManiKanth, S.R. Pandian, V. Deepak, S. Gurunathan (2010) Silver nanoparticles impede the biofilm formation by Pseudomonas aeruginosa and Staphylococcus epidermidis. Colloids Surf B Biointerfaces 79: 340-344.
16.
Kim, J.S., E. Kuk, K.N. Yu, J.H. Kim, S.J. Park, H.J. Lee, S.H. Kim, Y.K. Park, Y.H. Park, C.Y. Hwang, Y.K. Kim, Y.S. Lee, D.H. Jeong, M.H. Cho (2007) Antimicrobial effects of silver nanoparticles. Nanomedicine 3: 95-101.
17.
Kim, K.J., W.S. Sung, B.K. Suh, S.K. Moon, J.S. Choi, J.G. Kim, D.G. Lee (2009a) Antifungal activity and mode of action of silver nano-particles on Candida albicans. BioMetals 22: 235-242.
18.
Kim, S., J.E. Choi, J. Choi, K.H. Chung, K. Park, J. Yi, D.Y. Ryu (2009b) Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicol In Vitro 23: 1076-1084.
19.
Kim, T.H., M. Kim, H.S. Park, U.S. Shin, M.S. Gong, H.W. Kim (2012) Size-dependent cellular toxicity of silver nanoparticles. J Biomed Mater Res A 100: 1033-1043.
20.
Klein, C.L., S. Comero, B. Stahlmecke, J. Romazanov, T.A.J. Kuhlbusch, E. Van Doren, P.J. De Temmerman, J. Mast, P. Wick, H. Krug, G. Locoro, K. Hund-Rinke, W. Kördel, S. Friedrichs, G. Maier, J. Werner, T. Linsinger, B.M. Gawlik (2011) NM-Series of Representative Manufactured Nanomaterials. NM-300 Silver. Characterisation, Stability, Homogeneity. JRC Scientific and Technical Reports, http://publications.jrc.ec.europa.eu/repository/bitstream/111111111/16076/1/60709%20final_report_nm-300_08-09-2010%20final%202011%2001%20isbn.pdf (accessed March 2014).
21.
Lara, H.H., N.V. Ayala-Nuñez, L. Ixtepan-Turrent, C. Rodriguez-Padilla (2010a) Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotechnology 8: 1.
22.
Lara, H.H., N.V. Ayala-Núñez, L. Ixtepan-Turrent, C. Rodríguez-Padilla (2010b) Bactericidal effect of silver nanoparticles against multidrug-resistant bacteria. World J Microbiol Biotechnol 26: 615-621.
23.
Lentino, R. (2003) Prosthetic joint infections: bane of orthopedists, challenge for infectious disease specialists. Clin Infect Dis 36: 1157-1161.
24.
Lentino, J.R. (2004) Infections associated with prosthetic knee and prosthetic hip. Curr Infect Dis Rep 6: 388-392.
25.
Lu, L., R.W. Sun, R. Chen, C.K. Hui, C.M. Ho, J.M. Luk, G.K. Lau, C.M. Che (2008) Silver nanoparticles inhibit hepatitis B virus replication. Antivir Ther 13: 253-262.
26.
Matar, W.Y., S.M. Jafari, C. Restrepo, M. Austin, J.J. Purtill, J. Parvizi (2010) Preventing infection in total joint arthroplasty. J Bone Joint Surg Am 92: 36-46.
27.
Mohanty, S., S. Mishra, P. Jena, B. Jacob, B. Sarkar, A. Sonawane (2012) An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles. Nanomedicine 8: 916-924.
28.
Moreira, D.M., J. Oei, H.R. Rawls, J. Wagner, L. Chu, Y. Li, W. Zhang, K. Whang (2014) A novel antimicrobial orthodontic band cement with in situ-generated silver nanoparticles. Angle Orthod DOI: 10.2319/022314-127.1.
29.
Nagafusa, T., H. Hoshino, T. Sakurai, S. Terakawa, A. Nagano (2007) Mechanical fragmentation and transportation of calcium phosphate substrate by filopodia and lamellipodia in a mature osteoclast. Cell Biol Int 31: 1150-1159.
30.
Narducci, P., R. Bortul, R. Bareggi, V. Nicolin (2010) Clathrin-dependent endocytosis of membrane-bound RANKL in differentiated osteoclasts. Eur J Histochem 54: e6.
31.
Oei, J.D., W.W. Zhao, L. Chu, M.N. DeSilva, A. Ghimire, H.R. Rawls, K. Whang (2011) Antimicrobial acrylic materials with in situ generated silver nanoparticles. J Biomed Mater Res B Appl Biomater 100: 409-415.
32.
Pauksch, L., S. Hartmann, M. Rohnke, G. Szalay, V. Alt, R. Schnettler, K.S. Lips (2014) Biocompatibility of silver nanoparticles and silver ions in primary human mesenchymal stem cells and osteoblasts. Acta Biomater 10: 439-449.
33.
Peyrou, M., P.E. Hanna, A.E. Cribb (2007) Cisplatin, gentamicin, and p-aminophenol induce markers of endoplasmic reticulum stress in the rat kidneys. Toxicol Sci 99: 346-353.
34.
Prokopovich, P., M. Köbrick, E. Brousseau, S. Perni (2014) Potent antimicrobial activity of bone cement encapsulating silver nanoparticles capped with oleic acid. J Biomed Mater Res B Appl Biomater DOI: 10.1002/jbm.b.33196.
35.
Quiros, Y., L. Vicente-Vicente, A.I. Morales, J.M. López-Novoa, F.J. López-Hernández (2011) An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin. Toxicol Sci 119: 245-256.
36.
Renaud, A., M. Lavigne, P.A. Vendittoli (2012) Periprosthetic joint infections at a teaching hospital in 1990-2007. Can J Surg 55: 394-400.
37.
Saltel, F., O. Destaing, F. Bard, D. Eichert, P. Jurdic (2004) Apatite-mediated actin dynamics in resorbing osteoclasts. Mol Biol Cell 15: 5231-5241.
38.
Takito, J., M. Nakamura, M. Yoda, T. Tohmonda, S. Uchikawa, K. Horiuchi, Y. Toyama, K. Chiba (2012) The transient appearance of zipper-like actin superstructures during the fusion of osteoclasts. J Cell Sci 125: 662-672.
39.
Wang, Z., Y. Sun, D. Wang, H. Liu, R.I. Boughton (2013) In situ fabrication of silver nanoparticle-filled hydrogen titanate nanotube layer on metallic titanium surface for bacteriostatic and biocompatible implantation. Int J Nanomedicine 8: 2903-2916.
40.
Wei, Q., L.Z. Ma (2013) Biofilm matrix and its regulation in Pseudomonas aeruginosa. Int J Mol Sci 14: 20983-21005.
41.
Wright, J.B., K. Lam, R.E. Burrell (1998) Wound management in an era of increasing bacterial antibiotic resistance: a role for topical silver treatment. Am J Infect Control 26: 572-577.
42.
Zhang, B.G., D.E. Myers, G.G. Wallace, M. Brandt, P.F. Choong (2014) Bioactive coatings for orthopaedic implants - recent trends in development of implant coatings. Int J Mol Sci 15: 11878-11921.
43.
Zhang, R., M.J. Piao, K.C. Kim, A.D. Kim, J.Y. Choi, J. Choi, J.W. Hyun (2012) Endoplasmic reticulum stress signaling is involved in silver nanoparticles-induced apoptosis. Int J Biochem Cell Biol 44: 224-232.
44.
Zheng, Y., J. Li, X. Liu, J. Sun (2012) Antimicrobial and osteogenic effect of Ag-implanted titanium with a nanostructured surface. Int J Nanomedicine 7: 875-884.
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