Abstract
Ideal coatings for orthopedic implants should be able to induce excellent osseointegration with host bone tissue, which requires good osteogenic responses and limited inflammatory reactions. Cerium oxide (CeO2) ceramics have anti-oxidative properties and can be used to decrease mediators of inflammation, making them attractive for biomedical application. In this study, two kinds of CeO2 incorporated calcium silicate coatings (CS-10Ce and CS-30Ce) were prepared via plasma spraying technique, and the effects of CeO2 addition on the responses of bone mesenchymal stem cells (BMSCs) and RAW264.7 macrophages were evaluated. The CS-10Ce and CS-30Ce coatings were characterized by X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy. An increase in CeO2 content in the coatings resulted in enhanced chemical stability and better BMSCs osteogenic behaviors in terms of cell adhesion, proliferation, ALP activity, and mineralized nodule formation. With respect to either ZrO2-added or unmodified CS coating, the CS-30Ce coating elicited higher effects on the macrophages, suppressing the gene expressions of pro-inflammatory (M1) markers (CCR7, IL-6, and TNF-α), while upregulating the expressions of anti-inflammatory (M2) markers (CD206, IL-1ra, and IL-10); moreover, it could also increase the expression of osteoinductive molecules (BMP2 and TGF-β1) by the macrophages. The results suggested that the regulation of BMSCs behaviors and macrophage-mediated responses at the coating’s surface was related to CeO2 incorporation. The incorporation of CeO2 in CS coatings can be a valuable strategy to promote osteogenic responses and mitigate inflammatory reactions.
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References
Xue WC, Liu XY, Zheng XB, Ding CX (2005) In vivo evaluation of plasma-sprayed wollastonite coating. Biomaterials 26(17):3455–3460
Ni SY, Chang J, Chou L, Zhai WY (2007) Comparison of osteoblast-like cell responses to calcium silicate and tricalcium phosphate ceramics in vitro. J Biomed Mater Res B 80B(1):174–183
Liu XY, Morra M, Carpi A, Li B (2008) Bioactive calcium silicate ceramics and coatings. Biomed Pharmacother 62(8):526–529
Li K, Xie YT, You MY, Huang LP, Zheng XB (2016) Cerium oxide-incorporated calcium silicate coating protects MC3T3-E1 osteoblastic cells from H2O2-induced oxidative stress. Biol Trace Elem Res. doi:10.1007/s12011-016-0680-9
Heng BC, Cao T, Haider HK, Wang DZM, Sim EKW, Ng SC (2004) An overview and synopsis of techniques for directing stem cell differentiation in vitro. Cell Tissue Res 315(3):291–303
Niemeyer P, Fechner K, Milz S, Richter W, Suedkamp NP, Mehlhorn AT, Pearce S, Kasten P (2010) Comparison of mesenchymal stem cells from bone marrow and adipose tissue for bone regeneration in a critical size defect of the sheep tibia and the influence of platelet-rich plasma. Biomaterials 31(13):3572–3579
Liu Y, Yan F, Yang WL, XF L, Wang WB (2013) Effects of zinc transporter on differentiation of bone marrow mesenchymal stem cells to osteoblasts. Biol Trace Elem Res 154(2):234–243
Karakoti AS, Tsigkou O, Yue S, Lee PD, Stevens MM, Jones JR, Seal S (2010) Rare earth oxides as nanoadditives in 3-D nanocomposite scaffolds for bone regeneration. J Mater Chem 20(40):8912–8919
Mandoli C, Pagliari F, Pagliari S, Forte G, Di Nardo P, Licoccia S, Traversa E (2010) Stem cell aligned growth induced by CeO2 nanoparticles in PLGA scaffolds with improved bioactivity for regenerative medicine. Adv Funct Mater 20(10):1617–1624
Naganuma T, Traversa E (2014) The effect of cerium valence states at cerium oxide nanoparticle surfaces on cell proliferation. Biomaterials 35(15):4441–4453
Kzhyshkowska J, Gudima A, Riabov V, Dollinger C, Lavalle P, Vrana NE (2015) Macrophage responses to implants: prospects for personalized medicine. J Leukoc Biol 98(6):953–962
Sridharan R, Cameron AR, Kelly DJ, Kearney CJ, O’Brien FJ (2015) Biomaterial based modulation of macrophage polarization: a review and suggested design principles. Mater Today 18(6):313–325
Brown BN, Ratner BD, Goodman SB, Amar S, Badylak SF (2012) Macrophage polarization: an opportunity for improved outcomes in and regenerative medicine. Biomaterials 33(15):3792–3802
Chen LJ, Zhang YL, Liu J, Wei LM, Song B, Shao LQ (2016) Exposure of the murine RAW 264.7 macrophage cell line to dicalcium silicate coating: assessment of cytotoxicity and pro-inflammatory effects. J Mater Sci-Mater M 27(3):59
Hirst SM, Karakoti AS, Tyler RD, Sriranganathan N, Seal S, Reilly CM (2009) Anti-inflammatory properties of cerium oxide nanoparticles. Small 5(24):2848–2856
Linares J, Fernandez AB, Feito MJ, Matesanz MC, Sanchez-Salcedo S, Arcos D, Vallet-Regi M, Rojo JM, Portoles MT (2016) Effects of nanocrystalline hydroxyapatites on macrophage polarization. J Mater Chem B 4(11):1951–1959
Singh V, Karakoti A, Kumar A, Saha A, Basu S, Seal S (2010) Precursor dependent microstructure evolution and nonstoichiometry in nanostructured cerium oxide coatings using the solution precursor plasma spray technique. J Am Ceram Soc 93(11):3700–3708
Xie YT, Zheng XB, Ding CX, Zhai WY, Chang J, Ji H (2009) Preparation and characterization of CaO-ZrO2-SiO2 coating for potential application in biomedicine. J Therm Spray Techn 18(4):678–685
Liang Y, Xie YT, Ji H, Huang LP, Zheng XB (2010) Chemical stability and biological properties of plasma-sprayed CaO-SiO2-ZrO2 coatings. J Therm Spray Technol 19(6):1171–1178
Ramaswamy Y, Wu C, Van Hummel A, Combes V, Grau G, Zreiqat H (2008) The responses of osteoblasts, osteoclasts and endothelial cells to zirconium modified calcium-silicate-based ceramic. Biomaterials 29(33):4392–4402
Yi DL, CT W, Ma XB, Ji H, Zheng XB, Chang J (2012) Preparation and in vitro evaluation of plasma-sprayed bioactive akermanite coatings. Biomed Mater 7(6):065004
Li K, Yu JM, Xie YT, Huang LP, Ye XJ, Zheng XB (2011) Chemical stability and antimicrobial activity of plasma sprayed bioactive Ca2ZnSi2O7 coating. J Mater Sci-Mater M 22(12):2781–2789
Hu DD, Li K, Xie YT, Pan HH, Zhao J, Huang LP, Zheng XB (2016) Different response of osteoblastic cells to Mg2+, Zn2+ and Sr2+ doped calcium silicate coatings. J Mater Sci-Mater M 27(3):56
Liang Y, Xie YT, Ji H, Huang LP, Zheng XB (2010) Excellent stability of plasma-sprayed bioactive Ca3ZrSi2O9 ceramic coating on Ti-6Al-4V. Appl Surf Sci 256(14):4677–4681
Mohammadi H, Hafezi M, Nezafati N, Heasarki S, Nadernezhad A, Ghazanfari SMH, Sepantafar M (2014) Bioinorganics in bioactive calcium silicate ceramics for bone tissue repair: bioactivity and biological properties. J Ceram Sci Technol 5(1):1–12
Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (2007) Trends in oxidative aging theories. Free Radic Biol Med 43(4):477–503
Li K, Xie YT, You MY, Huang LP, Zheng XB (2016) Plasma sprayed cerium oxide coating inhibits H2O2-induced oxidative stress and supports cell viability. J Mater Sci-Mater M 27(6):100
Tarnuzzer RW, Colon J, Patil S, Seal S (2005) Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage. Nano Lett 5(12):2573–2577
Liu DD, Zhang JC, Li YP, Wang SX, Yang MS (2012) The effects of Ce on the proliferation, osteogenic differentiation and mineralization function of MC3T3-E1 cells in vitro. Biol Trace Elem Res 149(2):291–297
Xiang JY, Li JM, He J, Tang XY, Dou C, Cao Z, Yu B, Zhao CR, Kang F, Yang L, Dong SW, Yang XC (2016) Cerium oxide nanoparticle modified scaffold interface enhances vascularization of bone grafts by activating calcium channel of mesenchymal stem cells. ACS Appl Mater Interfaces 8(7):4489–4499
Chen ZT, Yuen J, Crawford R, Chang J, CT W, Xiao Y (2015) The effect of osteoimmunomodulation on the osteogenic effects of cobalt incorporated beta-tricalcium phosphate. Biomaterials 61:126–138
CT W, Chen ZT, QJ W, Yi DL, Friis T, Zheng XB, Chang J, Jiang XQ, Xiao Y (2015) Clinoenstatite coatings have high bonding strength, bioactive ion release, and osteoimmunomodulatory effects that enhance in vivo osseointegration. Biomaterials 71:35–47
Loi F, Cordova LA, Pajarinen J, Lin TH, Yao ZY, Goodman SB (2016) Inflammation, fracture and bone repair. Bone 86:119–130
Fei LS, Wang C, Xue Y, Lin KL, Chang J, Sun J (2012) Osteogenic differentiation of osteoblasts induced by calcium silicate and calcium silicate/beta-tricalcium phosphate composite bioceramics. J Biomed Mater Res B 100B(5):1237–1244
Heckert EG, Karakoti AS, Seal S, Self WT (2008) The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials 29(18):2705–2709
Korsvik C, Patil S, Seal S, Self WT (2007) Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem Commun 14(10):1056–1058
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This work was supported by the Natural Science Foundation of China (Grant Nos. 51502328, 81301537, 81300917) and the Opening Project of the Shanghai Key Laboratory of Orthopedic Implant (Grant No. KFKT2016003).
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Li, K., Yu, J., Xie, Y. et al. The Effects of Cerium Oxide Incorporation in Calcium Silicate Coating on Bone Mesenchymal Stem Cell and Macrophage Responses. Biol Trace Elem Res 177, 148–158 (2017). https://doi.org/10.1007/s12011-016-0859-0
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DOI: https://doi.org/10.1007/s12011-016-0859-0