Abstract
Hydroxyapatite (HAp, Ca10[PO4]6[OH]2) doped with numerous trace elements possesses sensational biochemical effects in natural bones. To study the biochemical function of Zn, Sr, and F elements, a series of neoteric HAp biomaterials with Zn, Sr, and F concentrations close to natural bones are firstly synthesized by one-pot hydrothermal method. These materials are characterized through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope (SEM). All the synthesized materials are HAp phase. The morphology of these materials is nanorods. The phenomenon that L929 cells can live even at 400 μg/mL powder concentration indicates that these materials are non-cytotoxic. The active effects of samples on proliferation and differentiation of osteoblast cells (MC3T3-E1) are certified by MTT and alkaline phosphatase (ALP) activity assays. The adhesion and proliferation of osteoblast measurement manifest that amounts of MC3T3-E1 advances about 1.86 times for ZnSrF/HAp compared with undoped HAp. This achievement may inspire us on the artificial design of new-style bionic bone grafts using trace bioactive elements and also suggest its latent applications in orthopedic surgery and bone osseointegration.
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References
Zhang R, Metoki N, Sharabani-Yosef O, Zhu H, Eliaz N (2016) Hydroxyapatite/mesoporous graphene/single-walled carbon nanotubes freestanding flexible hybrid membranes for regenerative medicine. Adv Funct Mate 26(44):7965–7974. https://doi.org/10.1002/adfm.201602088
Zhang T, Li N, Li KY, Gao RF, Gu W, CC W, RG S, Liu LW, Zhang Q, Liu J (2016) Enhanced proliferation and osteogenic differentiation of human mesenchymal stem cells on biomineralized three-dimensional graphene foams. Carbon 105:233–243. https://doi.org/10.1016/j.carbon.2016.04.027
Sadat-Shojai M, Khorasani MT, Dinpanah-Khoshdargi E, Jamshidi A (2013) Synthesis methods for nanosized hydroxyapatite with diverse structures. Acta Biomater 9(8):7591–7621. https://doi.org/10.1016/j.actbio.2013.04.012
Nakamura M, Hiratai R, Hentunen T, Salonen J, Yamashita K (2016) Hydroxyapatite with high carbonate substitutions promotes osteoclast resorption through osteocyte-like cells. Acs Biomater-Sci Eng 2(2):259–267. https://doi.org/10.1021/acsbiomaterials.5b00509
Hannig M, Hannig C (2010) Nanomaterials in preventive dentistry. Nat Nanotechnol 5(8):565–569. https://doi.org/10.1038/nnano.2010.83
Lee WH, Loo CY, Rohanizadeh R (2014) A review of chemical surface modification of bioceramics: effects on protein adsorption and cellular response. Colloid Surf B-Biointerfaces 122:823–834. https://doi.org/10.1016/j.colsurfb.2014.07.029
Lin K, Xia L, Gan J, Zhang Z, Chen H, Jiang X, Chang J (2013) Tailoring the nanostructured surfaces of hydroxyapatite bioceramics to promote protein adsorption, osteoblast growth, and osteogenic differentiation. ACS Appl Mater Interfaces 5(16):8008–8017. https://doi.org/10.1021/am402089w
Lin KL, Wang XH, Zhang N, Shen YH (2016) Strontium (Sr) strengthens the silicon (Si) upon osteoblast proliferation, osteogenic differentiation and angiogenic factor expression. J Mater Chem B 4(21):3632–3638. https://doi.org/10.1039/c6tb00735j
Boanini E, Gazzano M, Bigi A (2010) Ionic substitutions in calcium phosphates synthesized at low temperature. Acta Biomater 6(6):1882–1894. https://doi.org/10.1016/j.actbio.2009.12.041
Park SY, Kim KI, Park SP, Lee JH, Jung HS (2016) Aspartic acid-assisted synthesis of multifunctional strontium-substituted hydroxyapatite microspheres. Cryst Growth Des 16(8):4318–4326. https://doi.org/10.1021/acs.cgd.6b00420
Chen Z, Yi D, Zheng X, Chang J, Wu C, Xiao Y (2014) Nutrient element-based bioceramic coatings on titanium alloy stimulating osteogenesis by inducing beneficial osteoimmmunomodulation. J Mater Chem B 2(36):6030. https://doi.org/10.1039/c4tb00837e
Shi C, Gao JY, Wang M, Shao YR, Wang LP, Wang DL, Zhu YC (2016) Functional hydroxyapatite bioceramics with excellent osteoconductivity and stern-interface induced antibacterial ability. Biomater Sci 4(4):699–710. https://doi.org/10.1039/c6bm00009f
Huang Y, Zhang X, Mao H, Li T, Zhao R, Yan Y, Pang X (2015) Osteoblastic cell responses and antibacterial efficacy of Cu/Zn co-substituted hydroxyapatite coatings on pure titanium using electrodeposition method. RSC Adv 5(22):17076–17086. https://doi.org/10.1039/c4ra12118j
Cheng K, Weng WJ, Wang HM, Zhang S (2005) In vitro behavior of osteoblast-like cells on fluoridated hydroxyapatite coatings. Biomaterials 26(32):6288–6295. https://doi.org/10.1016/j.biomaterials.2005.03.041
Huo K, Zhang X, Wang H, Zhao L, Liu X, Chu PK (2013) Osteogenic activity and antibacterial effects on titanium surfaces modified with Zn-incorporated nanotube arrays. Biomaterials 34(13):3467–3478. https://doi.org/10.1016/j.biomaterials.2013.01.071
Gopi D, Karthika A, Rajeswari D, Kavitha L, Pramod R, Dwivedi J (2014) Investigation on corrosion protection and mechanical performance of minerals substituted hydroxyapatite coating on HELCDEB-treated titanium using pulsed electrodeposition method. RSC Adv 4(66):34751–34759. https://doi.org/10.1039/c4ra04484c
Pemmer B, Roschger A, Wastl A, Hofstaetter JG, Wobrauschek P, Simon R, Thaler HW, Roschger P, Klaushofer K, Streli C (2013) Spatial distribution of the trace elements zinc, strontium and lead in human bone tissue. Bone 57(1):184–193. https://doi.org/10.1016/j.bone.2013.07.038
Grandjean-Laquerrier A, Laquerriere P, Jallot E, Nedelec JM, Guenounou M, Laurent-Maquin D, Phillips TM (2006) Influence of the zinc concentration of sol-gel derived zinc substituted hydroxyapatite on cytokine production by human monocytes in vitro. Biomaterials 27(17):3195–3200. https://doi.org/10.1016/j.biomaterial.2006.01.024
Day RM, Boccaccini AR (2005) Effect of particulate bioactive glasses on human macrophages and monocytes in vitro. J Biomed Mater Res A 73A(1):73–79. https://doi.org/10.1002/jbm.a.30262
Haase H, Rink L (2007) Signal transduction in monocytes: the role of zinc ions. Biometals 20(3–4):579–585. https://doi.org/10.1007/s10534-006-9029-8
Velard F, Braux J, Amedee J, Laquerriere P (2013) Inflammatory cell response to calcium phosphate biomaterial particles: an overview. Acta Biomater 9(2):4956–4963. https://doi.org/10.1016/j.actbio.2012.09.035
Huang M, Hill RG, Rawlinson SCF (2017) Zinc bioglasses regulate mineralization in human dental pulp stem cells. Dent Mater 33(5):543–552. https://doi.org/10.1016/j.dental.2017.03.011
Querido W, Rossi AL, Farina M (2016) The effects of strontium on bone mineral: a review on current knowledge and microanalytical approaches. Micron 80:122–134. https://doi.org/10.1016/j.micron.2015.10.006
Schumacher M, Gelinsky M (2015) Strontium modified calcium phosphate cements - approaches towards targeted stimulation of bone turnover. J Mater Chem B 3(23):4626–4640. https://doi.org/10.1039/c5tb00654f
Marie PJ (2005) Strontium ranelate: a novel mode of action optimizing bone formation and resorption. Osteoporosis Int 16(S01):S7–S10. https://doi.org/10.1007/s00198-004-1753.8
Marie PJ, Ammann P, Boivin G, Rey C (2001) Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 69(3):121–129. https://doi.org/10.1007/s002230010055
Chattopadhyay N, Quinn SJ, Kifor O, Ye CP, Brown EM (2007) The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation. Biochem Pharmacol 74(3):438–447. https://doi.org/10.1016/j.bcp.2007.04.020
Skoryna SC (1981) Effects of oral supplementation with stable strontium. Can Med Assoc J 125(7):703–712
Wang YS, Zhang S, Zeng XT, Ma LL, Weng WJ, Yan WQ, Qian M (2007) Osteoblastic cell response on fluoridated hydroxyapatite coatings. Acta Biomater 3(2):191–197. https://doi.org/10.1016/j.actbio.2006.10.002
Cheng K, Weng WJ, Qu HB, Du PY, Shen G, Han GR, Yang J, Ferreira JMF (2004) Sol-gel preparation and in vitro test of fluorapatite/hydroxyapatite films. J Biomed Mater Res B 69B(1):33–37. https://doi.org/10.1002/jbm.b.20027
Kim HW, Kim HE, Knowles JC (2004) Fluor-hydroxyapatite sol-gel coating on titanium substrate for hard tissue implants. Biomaterials 25(17):3351–3358. https://doi.org/10.1016/j.biomaterials.2003.09.104
Wang M, Gao JY, Shi C, Zhu YC, Zeng Y, Wang DL (2014) Facile one-pot synthesis of oriented pure hydroxyapatite with hierarchical architecture by topotactic conversion. Cryst Growth Des 14(12):6459–6466. https://doi.org/10.1021/cg5013044
Sakai N, Fujishima A, Watanabe T, Hashimoto K (2003) Quantitative evaluation of the photoinduced hydrophilic conversion properties of TiO2 thin film surfaces by the reciprocal of contact angle. J Phys Chem B 107(4):1028–1035. https://doi.org/10.1021/jp022105p
Eslami H, Solati-Hashjin M, Tahriri M (2009) The comparison of powder characteristics and physicochemical, mechanical and biological properties between nanostructure ceramics of hydroxyapatite and fluoridated hydroxyapatite. Mater Sci Eng C 29(4):1387–1398. https://doi.org/10.1016/j.msec.2008.10.033
Chenu C, Colucci S, Grano M, Zigrino P, Barattolo R, Zambonin G, Baldini N, Vergnaud P, Delmas PD, Zallone AZ (1994) Osteocalcin induces chemotaxis, secretion of matrix proteins, and calcium-mediated intracellular signaling in human osteoclast-like cells. J Cell Biol 127(4):1149–1158. https://doi.org/10.1083/jcb.127.4.1149
Chen YM, Miao XG (2005) Thermal and chemical stability of fluorohydroxyapatite ceramics with different fluorine contents. Biomaterials 26(11):1205–1210. https://doi.org/10.1016/j.biomaterials.2004.04.027
Shi C, Gao JY, Wang M, Fu JK, Wang DL, Zhu YC (2015) Ultra-trace silver-doped hydroxyapatite with non-cytotoxicity and effective antibacterial activity. Mater Sci Eng C-Mater Biol Appl 55:497–505. https://doi.org/10.1016/j.msec.2015.05.078
Anselme K (2000) Osteoblast adhesion on biomaterials. Biomaterials 21(7):667–681. https://doi.org/10.1016/s0142-9612(99)00242-2
Wang Z, Telci D, Griffin M (2011) Importance of syndecan-4 and syndecan-2 in osteoblast cell adhesion and survival mediated by a tissue transglutaminase-fibronectin complex. Exp Cell Res 317(3):367–381. https://doi.org/10.1016/j.yexcr.2010.10.015
Tao Z-S, Zhou W-S, He X-W, Liu W, Bai B-L, Zhou Q, Huang Z-L, K-k T, Li H, Sun T, Lv Y-X, Cui W, Yang L (2016) A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C-Mater Biol Appl 62:226–232. https://doi.org/10.1016/j.msec.2016.01.034
Huang Y, Hao M, Nian XF, Qiao HX, Zhang XJ, Zhang XY, Song GQ, Guo JC, Pang XF, Zhang HL (2016) Strontium and copper co-substituted hydroxyapatite-based coatings with improved antibacterial activity and cytocompatibility fabricated by electrodeposition. Ceram Int 42(10):11876–11888. https://doi.org/10.1016/j.ceraminL2016.04.110
Sogo Y, Ito A, Fukasawa K, Sakurai T, Ichinose N (2004) Zinc containing hydroxyapatite ceramics to promote osteoblastic cell activity. Mater Sci Tech-Lond 20(9):1079–1083. https://doi.org/10.1179/026708304225019704
Capuccini C, Torricelli P, Boanini E, Gazzano M, Giardino R, Bigi A (2009) Interaction of Sr-doped hydroxyapatite nanocrystals with osteoclast and osteoblast-like cells. J Biomed Mater Res A 89A(3):594–600. https://doi.org/10.1002/jbm.a.31975
Hall SL, Dimai HP, Farley JR (1999) Effects of zinc on human skeletal alkaline phosphatase activity in vitro. Calcif Tissue Int 64(2):163–172. https://doi.org/10.1007/s002239900597
Huang M, Hill RG, Rawlinson SCF (2016) Strontium (Sr) elicits odontogenic differentiation of human dental pulp stem cells (hDPSCs): a therapeutic role for Sr in dentine repair? Acta Biomater 38:201–211. https://doi.org/10.1016/j.actbio.2016.04.037
Saidak Z, Marie PJ (2012) Strontium signaling: molecular mechanisms and therapeutic implications in osteoporosis. Pharmacol Ther 136(2):216–226. https://doi.org/10.1016/j.pharmthera.2012.07.009
Yang F, Yang DZ, Tu J, Zheng QX, Cai LT, Wang LP (2011) Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling. Stem Cells 29(6):981–991. https://doi.org/10.1002/stem.646
Bai Y, Bai Y, Gao J, Ma W, Su J, Jia R (2016) Preparation and characterization of reduced graphene oxide/fluorhydroxyapatite composites for medical implants. J Alloy Compd 688:657–667. https://doi.org/10.1016/j.jallcom.2016.07.006
Zhou J, Zhao L (2016) Multifunction Sr, Co and F co-doped microporous coating on titanium of antibacterial, angiogenic and osteogenic activities. Sci Rep 6(1):29069. https://doi.org/10.1038/srep29069
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We gratefully acknowledge the financial support by the National Natural Science Foundation of China (No. 51232007, 51072217, 51572283) and the Science and Technology Commission of Shanghai Municipality: (No. 08JC1420700 and No. 11XD1405600).
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Xiao, S., Wang, M., Wang, L. et al. Environment-Friendly Synthesis of Trace Element Zn, Sr, and F Codoping Hydroxyapatite with Non-cytotoxicity and Improved Osteoblast Proliferation and Differentiation. Biol Trace Elem Res 185, 148–161 (2018). https://doi.org/10.1007/s12011-017-1226-5
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DOI: https://doi.org/10.1007/s12011-017-1226-5