Preparation of CaO-SiO2-CuO bioactive glasses-embedded anodic alumina with improved biological activities

Siyu Ni 1 , 2 , Lin Mei 3 , Shirong Ni 4 , Ran Cui 2 , Xiaohong Li 3 , Feng Hong 3 , Thomas J. Webster 5  and Chengtie Wu 6
  • 1 Key Lab of Eco-Textile, Ministry of Education, Donghua University, North Renmin Road 2999, , Shanghai, China
  • 2 College of Chemistry, Chemical Engineering and Biotechnology; Donghua University, North Renmin Road 2999, , Shanghai, China
  • 3 College of Chemistry, Chemical Engineering and Biotechnology; Donghua University, North Renmin Road 2999, , Shanghai, China
  • 4 Department of Pathology, Zhejiang Chinese Medical University, , Hangzhou, China
  • 5 Department of Chemical Engineering, College of Engineering, Northeastern University, , Boston, United States of America
  • 6 State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, , Shanghai , China


To improve bone cell cytocompatibility properties of porous anodic alumina (PAA) and implement anti-bacterial properties, amorphous CaO-SiO2-CuO materials were loaded into PAA nano-pores (termed CaO-SiO2- CuO/PAA) by a facile ultrasonic-assisted sol-dipping strategy. The surface features and chemistry of the obtained CaO-SiO2-CuO/PAA were investigated by a field emission scanning microscope (FESEM), an energy-dispersive Xray spectrometer (EDS) and an X-ray photoelectron spectroscopy (XPS). The ability of the CaO-SiO2-CuO/PAA specimens to form apatite via a bio-mineralization processwas evaluated by soaking them in simulated body fluid (SBF) in vitro. The surface microstructure and chemical properties after soaking in SBFwere characterized. The release of ions into the SBF was also measured. In addition, rat osteoblasts and two types of bacterial were cultured on the samples to determine their cytocompatibility and antibacterial properties. The results showed that the amorphous CaO-SiO2-CuO materials were successfully decorated into PAA nano-pores and at the same time maintained their nano-featured surfaces. The CaO-SiO2-CuO/PAA samples induced apatite-mineralization in SBF. Meanwhile, the CaO-SiO2-CuO/PAA samples demonstrated great potential for promoting the proliferation of osteoblasts and inhibiting Escherichia coli (E. coli) as well as Staphylococcus. aureus (S. aureus) growth. Specifically, there was an 86.5±4.1% reduction in E. coli, an 88.0 ± 2.2% reduction in S. aureus for the CaO-SiO2-CuO/PAA surfaces compared to PAA controls. The capability to promote osteoblast proliferation and better antibacterial activity of CaO-SiO2- CuO/PAA may be attributed to the fact that Cu ions can be slowly and constantly released from the samples. Importantly, this was achieved without the use of antibiotics or any pharmaceutical agent. Ultimately, these results suggest that the CaO-SiO2-CuO/PAA substrates possessed improved bone cell cytocompatibility and high antibacterial properties leading to a promising bioactive coating candidate for enhanced orthopedic applications.

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  • [1] Brüggemann D., Nanoporous aluminium oxide membranes as cell interfaces, J. Nanomater., 2013, 2013, 1-18.

  • [2] Chen W., Wu J.S., Xia X.H., Porous anodic alumina with continuously manipulated pore/cell size, ACS Nano, 2008, 2, 959-965.

  • [3] Li X.H., Ni S.Y., Webster T.J., In vitro apatite formation on porous anodic alumina induced by a phosphorylation treatment, J. Biomater. Appl., 2014, 29, 321-328.

  • [4] Chung S.H., Son S.J., Min J., The nanostructure effect on the adhesion and growth rates of epithelial cells with well-defined nanoporous alumina substrates, Nanotechnology, 2010, 21, 125104.

  • [5] Wang H.J., Sun Y.Y., Cao Y., Wang K., Yang L., Zhang Y.D., Zheng Z., Is there an optimal topographical surface in nanoscale affecting protein adsorption and cell behaviors? Part II, J. Nanopart. Res., 2012, 14, 862-871.

  • [6] Thakure S., Massou S., Benoliel A.M., Bongrand P., Hanbucken M., Sengupta K., Depthmatters: cells grown on nano-porous anodic alumina respond to pore depth, Nanotechnology, 2012, 23, 255101.

  • [7] Pedimonte B.J., Moest T., Luxbacher T., von Wilmowsky C., Fey T., Schlegel K.A., Greil P., Morphological zeta-potential variation of nanoporous anodic alumina layers and cell adherence, Acta Biomater., 2014, 10, 968-974.

  • [8] Ma S.H., Scaraggi M., Wang D.A., Wang X.L., Liang Y.M., Liu W.M., Dini D., Zhou F., Nanoporous Substrate-infiltrated hydrogels: a bioinspired regenerable surface for high load bearing andtunable friction, Adv. Funct. Mater., 2015, 25, 7366-7374.

  • [9] Ni S.Y., Li C.Y., Ni S.R., Chen T., Webster T.J., Understanding improved osteoblast behavior on select nanoporous anodic alumina, Int. J. Nanomed., 2014, 9, 3325-3334.

  • [10] Chen Z.T, Ni S.Y., Han S.W., Crawford R., Lu S., Wei F., Chang J., Wu C.T., Xiao Y., Nanoporous microstructures mediate osteogenesis by modulating the osteo-immune response of macrophages, Nanoscale, 2017, 9, 706-718.

  • [11] Walpole A.R., Xia Z.D., Wilson C.W., Trifltt J.T., Wilshaw P. R., A novel nano-porous alumina biomaterial with potential for loading with bioactive materials, J. Biomed. Mater. Res. A, 2009, 90A, 46-54.

  • [12] Briggs E.P., Walpole A.R., Wilshaw P.R., Formation of highly adherent nano-porous alumina on Ti-based substrates: a novel bone implant coating, J. Maer. Sci. - Mater. M., 2004, 15, 1021-1029.

  • [13] Norman J.J., Desai T.A., Methods for fabrication of nanoscale topography for tissue engineering scaffolds, Ann. Biomed. Eng., 2006, 34, 89-101.

  • [14] Offermanns V., Andersen O. Z., Riede G., Andersen I. H., Almtoft K.P., Sørensen S., Sillassen M., Jeppesen C.S., Rasse M., Foss M., Kloss F., Bone regenerating effect of surface-functionalized titanium implants with sustained-release characteristics of strontium in ovariectomized rats, Int. J. Nanomed., 2016, 11, 2431-2442.

  • [15] Hu H., Zhang W., Oiao Y., Jiang X., Liu X., Ding C., Antibacterial activity and increased bone marrow stem cell functions of Znincorporated TiO2coatings on titanium, Acta Biomater., 2012, 8, 904-915.

  • [16] Ni S.Y., Chang J., In vitro degradation, bioactivity, and cytocompatibility of calcium silicate, dimagnesium silicate, and tricalcium phosphate bioceramics, J. Biomater. Appl., 2009, 24, 139-158.

  • [17] Wu C.T., Chang J., A review of bioactive silicate ceramics, Biomed. Mater. 2013, 8, 032001.

  • [18] Hench L.L., The story of bioglass, J.Mater. Sci. -Mater. M., 2006, 17, 967-978.

  • [19] Dermience M., Lognay G.,Mathieu F., Goyens P., Effects of thirty elements on bone metabolism, J. Trace Elem. Med. Biol., 2015, 6, 86-106.

  • [20] Wu C., Zhou Y., Xu M., Han P., Chen L., Chang J., Xiao Y., Coppercontaining mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity, Biomaterials, 2013, 34, 422-433.

  • [21] Shi M., Chen Z., Farnaghi S., Friis T., Mao X., Xiao Y., Wu C., Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis, Acta Biomater., 2016, 30, 334-344.

  • [22] Stähli C., James-Bhasin M., Hoppe A., Boccaccini A.R., Nazhat S.N., Effect of ion release from Cu-doped 45S5 Bioglassr on 3D endothelial cell morphogenesis, Acta Biomater., 2015,19, 15-22.

  • [23] Hoppe A., Meszaros R., Stähli C., Romeis S., Schmidt J., Peukert W., Marelli B., Nazhat S.N., Wondraczek L., Lao J., Jallot E., Boccaccini A.R., In vitro reactivity of Cu doped 45S5 Bioglassr Derived scaffolds for bone tissue engineering, J. Mater. Chem. B, 2013, 1, 5659-5674.

  • [24] Ren L., Wong H.M., Yan C.H., Yeung K.W.K., Yang K., Osteogenic ability of Cu-bearing stainless steel, J. Biomed., Mater., Res., Part B: Appl. Biomater., 2015, 103B, 1433-1444.

  • [25] Tian T., Wu C., Chang J., Preparation and in vitro osteogenic, angiogenic and antibacterial properties of cuprorivaite (CaCuSi4O10, Cup) bioceramics, RSC Adv., 2016, 6, 45840-45849.

  • [26] Kong N., Lin K., Li H., Chang J., Synergy effects of copper and silicon ions on stimulation of vascularization by copper-doped calcium silicate, J. Mater. Chem. B, 2014, 2, 1100-1110.

  • [27] Li X.H., Ni S.Y., Zhou X.P., Highly ordered porous anodic alumina with large diameter pores fabricated by an improved two-step anodization approach., J. Nanosci. Nanotechno., 2015, 15, 1725-1731.

  • [28] Kokubo T., Takadama H., How useful is SBF in predicting in vivo bone bioactivity?, Biomaterials, 2006, 27, 2907-2915.

  • [29] Ni S.Y., Chang J., Chou L., A novel bioactive porous CaSiO3 scaffold for bone tissue engineering, J. Biomed.Mater. Res. A, 2006, 76A, 196-205.

  • [30] Ni S.Y., Chang J., Chou L., Comparison of osteoblast-like cell responses to calcium silicate and tricalcium phosphate ceramics in vitro, J. Biomed. Mater. Res. Part B: Appl. Biomater., 2007, 80B, 174-183.

  • [31] Zhang W., Du K., Yan C., Wang F., Preparation and characterization of a novel Si-incorporated ceramic film on pure titanium by plasma electrolytic oxidation, Appl. Surf. Sci., 2008, 254, 5216-5223.

  • [32] Liu P., Hensen E.J.M., Highly Eflcient and robust Au/MgCuCr2O4 catalyst for gas-phase oxidation of ethanol to acetaldehyde, J. Am. Chem. Soc., 2013, 135, 14032-14035.

  • [33] Ni S.Y., Li X. H., Yang P.A., Ni S.R., Hong F., Webster T.J., Enhanced apatite-forming ability and antibacterial activity of porous anodic alumina embedded with CaO-SiO2-Ag2O bioactive materials, Mat. Sci. Eng C - Mater., 2016, 58, 700-708.

  • [34] Asharani P.V., Wu Y.L., Gong Z.Y., Valiyaveettil S., Toxicity of silver nanoparticles in zebrafish models, Nanotechnology, 2008, 19, 255102.

  • [35] Park E.J., Yi J., Kim Y., Choi K., Park K., Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism, Toxicol. in vitro, 2010, 24, 872-878.

  • [36] Zhao L., Wang H., Huo K., Cui L., Zhang W., Ni H., Zhang Y., Wu Z., Chu P.K., Antibacterial nano-structured titania coating incorporated with silver nanoparticles, Biomaterials, 2011, 32, 5706-5716.

  • [37] Wu C., Chang J., Fan W., Bioactive mesoporous calcium-silicate nanoparticles with excellent mineralization ability, osteostimulation, drug-delivery and antibacterial properties for filling apex roots of teeth, J. Mater. Chem., 2012, 22, 16801-16809.

  • [38] Abiaka C., Olusi S., Al-Awadhi A., Reference ranges of copper and zinc and the prevalence of their deficiencies in an Arab population aged 15-80 years, Biol. Trace Elem. Res., 2003, 91, 33-43.

  • [39] Sanchez C., Lopez-Jurado M., Aranda P., Llopis J., Plasma levels of copper, manganese and selenium in an adult population in southern Spain: Influence of age, obesity and lifestyle factors, Sci. Total Environ., 2010, 408, 1014-1020.

  • [40] Baranowska M., Slota A.J., Eravuchira P.J., Macias G., Xifré- Pérez E., Pallares J., Ferré-Borrull J., Marsal L.F., Protein attachment to nanoporous anodic alumina for biotechnological applications: Influence of pore size, protein size and functionalization path, Colloid. Surface. B, 2014, 122, 375-383.

  • [41] Roach P., Farrar D., Perry C.C., Surface tailoring for controlled protein adsorption: effect of topography at the nanometer scale and chemistry, J. Am. Chem. Soc., 2006, 128, 3939-3945.

  • [42] Wu S., Weng Z., Liu X., Yeung K.W.K., Chu P.K., Functionalized TiO2 based nanomaterials for biomedical applications, Adv. Funct. Mater., 2014, 24, 5464-5481.

  • [43] Xu Z., Li M., Li X., Liu X., Ma F., Wu S., Yeung K.W.K., Han Y., Chu P.K., Antibacterial activity of silver doped titanate nanowires on Ti implants, ACS Appl. Mater. Interfaces, 2016, 8, 16584-16594.

  • [44] Goh Y.F., Alshemary A.Z., Akram M., Bioactive Glass: An In-vitro comparative study of doping with nanoscale copper and silver particles, Int. J. Appl. Glass Sci., 2014, 5, 255-266.

  • [45] Goudouri O.M., Kontonasaki E., Lohbauer U., Boccaccini A.R., Antibacterial properties of metal and metalloid ions in chronic periodontitis and peri-implantitis therapy, Acta Biomater., 2014, 10, 3795-3810.


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Biomedical Glasses is an international open access journal covering the field of glasses for biomedical applications. The aim of the journal is to provide a peer-reviewed forum for the publication of original research reports and authoritative review articles related to the development of biomedical glasses and their use in clinical applications.