Abstract
Infection in bone transplantation process is attracting considerable attention. The current study synthesizes silver/strontium co-substituted hydroxyapatite (Ag/Sr-HA) nanoparticles with combined osteogenic and antibacterial activities. Different concentrations of silver-substituted hydroxyapatite (Ag-HA) nanoparticles were synthesized by hydrothermal method, and then their physicochemical properties were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscope (TEM), and energy-dispersive X-ray spectroscopy (EDS). Then, Sr was added as secondary element into Ag-HA to improve the biocompatibility of substrate. The antibacterial experiments indicated that Ag-HA had excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The effects of prepared samples on cell proliferation and differentiation were evaluated using MC3T3-E1 cells in vitro. The results showed that Sr substitution enhanced cell proliferation and differentiation, upregulated expression of osteogenic genes, and induced mineralization of cells. The substitution of Sr in Ag/Sr-HA nanoparticles can effectively alleviate the negative effects of Ag and enhance the biological activity of HA. Thus, the synthesized Ag/Sr-HA nanoparticles will serve as a potential candidate for application of biomedical implants with excellent osteogenic and antibacterial ability.
Similar content being viewed by others
References
Habraken W, Habibovic P, Epple M, Bohner M (2016) Calcium phosphates in biomedical applications: materials for the future. Mater Today 19:69–87. https://doi.org/10.1016/j.mattod.2015.10.008
Guha AK, Singh S, Kumaresan R, Nayar S, Sinha A (2009) Mesenchymal cell response to nanosized biphasic calcium phosphate composites. Colloids Surf B Biointerfaces 73:146–151. https://doi.org/10.1016/j.colsurfb.2009.05.009
Ruchholtz S, Täger G, Nastkolb D (2004) The infected hip prosthesis. Unfallchirurg 107:307–317. https://doi.org/10.1007/s00113-004-0751-9
Huang Y, Ding Q, Han S, Yan Y, Pang X (2013) Characterisation, corrosion resistance and in vitro bioactivity of manganese-doped hydroxyapatite films electrodeposited on titanium. J Mater Sci Mater Med 24:1853–1864. https://doi.org/10.1007/s10856-013-4955-9
Campoccia D, Montanaro L, Arciola CR (2006) The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials 27:2331–2339. https://doi.org/10.1016/j.biomaterials.2005.11.044
Anghelina FV, Ungureanu DN, Bratu V, Popescu IN, Rusanescu CO (2013) Fine structure analysis of biocompatible ceramic materials based hydroxyapatite and metallic biomaterials 316 L. Appl Surf Sci 285:65–71. https://doi.org/10.1016/j.apsusc.2013.06.102
Riaz M, Zia R, Saleemi F, Ikram H, Bashir F (2015) In vitro antimicrobial activity of ZnO based glass-ceramics against pathogenic bacteria. J Mater Sci Mater Med 26:268–279. https://doi.org/10.1007/s10856-015-5603-3
Qin Q, Li J, Wang J (2016) Antibacterial activity comparison of three metal oxide nanoparticles and their dissolved metal ions. Water Environ Res 89:378–383. https://doi.org/10.2175/106143017X14839994523262
Gabriel JS, Gonzaga VAM, Poli AL, Schmitt CC (2017) Photochemical synthesis of silver nanoparticles on chitosans/montmorillonite nanocomposite films and antibacterial activity. Carbohyd Polym 171:202–210. https://doi.org/10.1016/j.carbpol.2017.05.021
Karbowniczek J, Cordero-Arias L, Virtanen S, Misra SK, Valsami-Jones E, Tuchscherr L, Rutkowski B, Górecki K, Bała P, Czyrska-Filemonowicz A (2017) Electrophoretic deposition of organic/inorganic composite coatings containing ZnO nanoparticles exhibiting antibacterial properties. Mater Sci Eng C 77:780–789. https://doi.org/10.1016/j.msec.2017.03.180
Azeena S, Subhapradha N, Selvamurugan N, Narayan S, Srinivasan N, Murugesan R, Chung TW, Moorthi A (2016) Antibacterial activity of agricultural waste derived wollastonite doped with copper for bone tissue engineering. Mater Sci Eng C 71:1156–1165. https://doi.org/10.1016/j.msec.2016.11.1180
Kunkalekar RK, Prabhu MS, Naik MM, Salker AV (2014) Silver-doped manganese dioxide and trioxide nanoparticles inhibit both gram positive and gram negative pathogenic bacteria. Colloids Surf B Biointerfaces 113:429–434. https://doi.org/10.1016/j.colsurfb.2013.09.036
Peetsch A, Greulich C, Braun D, Stroetges C, Rehage H, Siebers B, Koller M, Epple M (2013) Silver-doped calcium phosphate nanoparticles: synthesis, characterization, and toxic effects toward mammalian and prokaryotic cells. Colloids Surf B Biointerfaces 102:724–729. https://doi.org/10.1016/j.colsurfb.2012.09.040
Jamuna-Thevi K, Bakar SA, Ibrahim S, Shahab N, Toff MRM (2011) Quantification of silver ion release, in vitro cytotoxicity and antibacterial properties of nanostuctured Ag doped TiO2 coatings on stainless steel deposited by RF magnetron sputtering. Vacuum 86:235–241. https://doi.org/10.1016/j.vacuum.2011.06.011
Gopi D, Shinyjoy E, Kavitha L (2014) Synthesis and spectral characterization of silver/magnesium co-substituted hydroxyapatite for biomedical applications. Spectrochim Acta A 127:286–291. https://doi.org/10.1016/j.saa.2014.02.057
Jin GD, Qin H, Cao HL, Qian S, Zhao YC, Peng XC, Zhang XL, Liu XY, Chu PK (2014) Synergistic effects of dual Zn/Ag ion implantation in osteogenic activity and antibacterial ability of titanium. Biomaterials 35:7699–7713. https://doi.org/10.1016/j.biomaterials.2014.05.074
Bari A, Bloise N, Fiorilli S, Novajra G, Vallet-Regí M, Bruni G, Torres-Pardo A, González-Calbet JM, Visai L, Vitale-Brovarone C (2017) Copper-containing mesoporous bioactive glass nanoparticles as multifunctional agent for bone regeneration. Acta Biomater 55:493–504. https://doi.org/10.1016/j.actbio.2017.04.012
Liu J, Rawlinson SC, Hill RG, Fortune F (2016) Strontium-substituted bioactive glasses in vitro osteogenic and antibacterial effects. Dent Mater 32:412–422. https://doi.org/10.1016/j.dental.2015.12.013
Gentleman E, Fredholm YC, Jell G, Lotfibakhshaiesh N, O'Donnell MD, Hill RG, Stevens MM (2010) The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro. Biomaterials 31:3949–3956. https://doi.org/10.1016/j.biomaterials.2010.01.121
Yang F, Tu J, Yang D, Li G, Cai L, Wang L (2010) Osteogenic differentiation of mesenchymal stem cells could be enhanced by strontium. Eng Med Biol Soc 2010:823–826. https://doi.org/10.1109/IEMBS.2010.5626774
Atkins GJ, Welldon KJ, Halbout P, Findlay DM (2009) Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteopor Int 20:653–664. https://doi.org/10.1007/s00198-008-0728-6
Lei Y, Xu Z, Ke Q, Yin W, Chen Y, Zhang C, Guo Y (2017) Strontium hydroxyapatite/chitosan nanohybrid scaffolds with enhanced osteoinductivity for bone tissue engineering. Mater Sci Eng C 72:134–142. https://doi.org/10.1016/j.msec.2016.11.063
Kheradmandfard M, Fathi MH (2013) Fabrication and characterization of nanocrystalline Mg-substituted fluorapatite by high energy ball milling. Ceram Int 39:1651–1658. https://doi.org/10.1016/j.ceramint.2012.08.007
Bigi A, Falini G, Foresti E, Gazzano M, Ripmonti A, Roveri N (1996) Rietveld structure refinements of calcium hydroxylapatite containing magnesium. Acta Crystallogr B 52:87–92. https://doi.org/10.1107/S0108768195008615
Ren F, Xin R, Ge X, Leng Y (2009) Characterization and structural analysis of zinc-substituted hydroxyapatites. Acta Biomater 5:3141–3149. https://doi.org/10.1016/j.actbio.2009.04.014
Xiu ZL, Lü MK, Liu SW, Zhou GJ, Su BY, Zhang HP (2005) Barium hydroxyapatite nanoparticles synthesized by citric acid sol–gel combustion method. Mater Res Bull 40:1617–1622. https://doi.org/10.1016/j.materresbull.2005.04.033
Wang LP, Pathak JL, Liang DL, Zhong NY, Guan HB, Wan MJ, Miao GH, Li ZM, Ge LH (2020) Fabrication and characterization of strontium- hydroxyapatite/silk fibroin biocomposite nanospheres for bone-tissue engineering applications. Int J Biol Sci 142:366–375. https://doi.org/10.1016/j.ijbiomac.2019.09.107
Roy M, Fielding GA, Beyenal H, Bandyopadhyay A, Bose S (2012) Mechanical, in vitro antimicrobial and biological properties of plasma sprayed silver-doped hydroxyapatite coating. ACS Appl Mater Interfaces 4:1341–1349. https://doi.org/10.1021/am201610q
Takaoka S, Yamaguchi T, Yano S, Yamauchi M, Sugimoto T (2010) The Calcium-sensing Receptor (CaR) is involved in strontium ranelate-induced osteoblast differentiation and mineralization. Horm Metab Res 42:627–631. https://doi.org/10.1055/s-0030-1255091
Gaharwar AK, Mihaila SM, Swami A, Patel A, Sant S, Reis RL, Marques AP, Gomes ME, Khademhosseini A (2013) Bioactive silicate nanoplatelets for osteogenic differentiation of human mesenchymal stem cells. Adv Mater 25:3329–3336. https://doi.org/10.1002/adma.201300584
Zhao LZ, Wang HR, Huo KF, Zhang XM, Wang W, Zhang YMWZF, Chu PK (2013) The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates. Biomaterials 34:19–29. https://doi.org/10.1016/j.biomaterials.2012.09.041
Xu K, Chen W, Mu C, Yu Y, Cai K (2017) Strontium folic acid derivative functionalized titanium surfaces for enhanced osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo. J Mater Chem B 5:6811–6826. https://doi.org/10.1039/C7TB01529A
Xing M, Wang X, Wang E, Gao L, Chang J (2018) Bone tissue engineering strategy based on the synergistic effects of silicon and strontium ions. Acta Biomater 72:381–395. https://doi.org/10.1016/j.actbio.2018.03.051
Funding
This work was supported by the National Natural Science Foundation of China (21471044), the Natural Science Foundation of Hebei Province (B2020201020), the Science and Technology Projects of Hebei Education Department (ZD2020150), the Third Batch of Top Youth Talent Support Program of Hebei Province, the Priority Strategy Project of Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education (ts2019006), Medical Science Foundation of Hebei University (2020A03), and the Post-graduate,s Innovation Fund Project of Hebei University (hbu2020ss012).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Li, Y., Wang, W., Han, J. et al. Synthesis of Silver- and Strontium-Substituted Hydroxyapatite with Combined Osteogenic and Antibacterial Activities. Biol Trace Elem Res 200, 931–942 (2022). https://doi.org/10.1007/s12011-021-02697-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-021-02697-z