Abstract: To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical applications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.

LO2细胞3-D模型用于四种纳米银包裹的牙科合金材料毒性的检测

[1]Al-Hiyasat AS, Bashabsheh OM, Darmani H, 2002. Elements released from dental casting alloys and their cytotoxic effects. Int J Prosthodont, 15(5):473-478.

[2]Aksakal B, Yildirim OS, Gul H, 2004. Metallurgical failure analysis of various implant materials used in orthopedic applications. J Fail Anal Prev, 4(3):17-23.

[3]Allaker RP, 2010. The use of nanoparticles to control oral biofilm formation. J Dent Res, 89(11):1175-1186.

[4]AshaRani PV, Mun GLK, Hande MP, et al., 2009. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano, 3(2):279-290.

[5]Burcham PC, 2014. Target-organ toxicity: liver and kidney. In: An Introduction to Toxicology. Springer London, p.151-187.

[6]Chu Q, Zhao Y, Shi X, et al., 2017. In vivo-like 3-D model for sodium nitrite- and acrylamide-induced hepatotoxicity tests utilizing HepG2 cells entrapped in micro-hollow fibers. Sci Rep, 7(1):14837.

[7]Dambach DM, Andrews BA, Moulin F, 2005. New technologies and screening strategies for hepatotoxicity: use of in vitro models. Toxicol Pathol, 33(1):17-26.

[8]de Bartolo L, Salerno S, Morelli S, et al., 2006. Long-term maintenance of human hepatocytes in oxygen-permeable membrane bioreactor. Biomaterials, 27(27):4794-4803.

[9]Fadeel B, Garcia-Bennett AE, 2010. Better safe than sorry: understanding the toxicological properties of inorganic nanoparticles manufactured for biomedical applications. Adv Drug Deliv Rev, 62(3):362-374.

[10]García-Contreras R, Argueta-Figueroa L, Mejía-Rubalcava C, et al., 2011. Perspectives for the use of silver nanoparticles in dental practice. Int Dent J, 61(6):297-301.

[11]Gómez-Lechón MJ, Castell JV, Donato MT, 2007. Hepatocytes—the choice to investigate drug metabolism and toxicity in man: in vitro variability as a reflection of in vivo. Chem Biol Interact, 168(1):30-50.

[12]Hamouda IM, 2012. Current perspectives of nanoparticles in medical and dental biomaterials. J Biomed Res, 26(3): 143-151.

[13]Hanawa T, 2002. Evaluation techniques of metallic biomaterials in vitro. Sci Technol Adv Mater, 3(4):289-295.

[14]Hiromoto S, Noda K, Hanawa T, 2002. Development of electrolytic cell with cell-culture for metallic biomaterials. Corros Sci, 44(5):955-965.

[15]Hussain SM, Hess KL, Gearhart JM, et al., 2005. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol in Vitro, 19(7):975-983.

[16]Kino Y, Sawa M, Kasai S, et al., 1998. Multiporous cellulose microcarrier for the development of a hybrid artificial liver using isolated hepatocytes. J Surg Res, 79(1):71-76.

[17]Kittler S, Greulich C, Diendorf J, et al., 2010. Toxicity of silver nanoparticles increases during storage because of slow dissolution under release of silver ions. Chem Mater, 22(16):4548-4554.

[18]Kmieć Z, 2001. Cooperation of liver cells in the synthesis and degradation of eicosanoids. In: Cooperation of Liver Cells in Health and Disease. Springer Berlin Heidelberg, p.51-59.

[19]Li Y, Lv XL, 2001. Research progress of modification of poly (vinylidene fluoride) porous membrane. J Tianjin Polytech Univ, 5:74-78.

[20]Manivasagam G, Dhinasekaran D, Rajamanickam A, 2010. Biomedical implants: corrosion and its prevention— a review. Recent Pat Corros Sci, 2(1):40-54.

[21]Mizumoto H, Ishihara K, Nakazawa K, et al., 2008. A new culture technique for hepatocyte organoid formation and long-term maintenance of liver-specific functions. Tissue Eng Part C Methods, 14(2):167-175.

[22]Morones JR, Elechiguerra JL, Camacho A, et al., 2005. The bactericidal effect of silver nanoparticles. Nanotechnology, 16(10):2346-2353.

[23]Niinomi M, Hattori T, Morikawa K, et al., 2002. Development of low rigidity β-type titanium alloy for biomedical applications. Mater Trans, 43(12):2970-2977.

[24]Ren YB, Yang C, Liang Y, 2002. Research and development of new biomedical metallic material. Mater Rev, 16(2): 12-15.

[25]Schmalz G, Langer H, Schweikl H, 1998. Cytotoxicity of dental alloy extracts and corresponding metal salt solutions. J Dent Res, 77(10):1772-1778.

[26]Silva T, Pokhrel LR, Dubey B, et al., 2014. Particle size, surface charge and concentration dependent ecotoxicity of three organo-coated silver nanoparticles: comparison between general linear model-predicted and observed toxicity. Sci Total Environ, 468-469:968-976.

[27]Sung JH, Ji JH, Yoon JU, et al., 2008. Lung function changes in Sprague-Dawley rats after prolonged inhalation exposure to silver nanoparticles. Inhal Toxicol, 20(6):567-574.

[28]Wataha JC, 2000. Biocompatibility of dental casting alloys: a review. J Prosth Dent, 83(2):223-234.

[29]Wong KKY, Cheung SOF, Huang L, et al., 2009. Further evidence of the anti-inflammatory effects of silver nanoparticles. Chem Med Chem, 4(7):1129-1135.

[30]Yamamoto A, Honma R, Sumita M, 1998. Cytotoxicity evaluation of 43 metal salts using murine fibroblasts and osteoblastic cells. J Biomed Mater Res, 39(2):331-340.

[31]Zreiqat H, Howlett CR, Zannettino A, et al., 2002. Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants. J Biomed Mater Res, 62(2):175-184.