Skip to main content

Advertisement

Log in

Environment-Friendly Synthesis of Trace Element Zn, Sr, and F Codoping Hydroxyapatite with Non-cytotoxicity and Improved Osteoblast Proliferation and Differentiation

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. 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

    Article  CAS  Google Scholar 

  2. 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

    Article  CAS  Google Scholar 

  3. 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

    Article  CAS  PubMed  Google Scholar 

  4. 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

    Article  CAS  PubMed  Google Scholar 

  5. Hannig M, Hannig C (2010) Nanomaterials in preventive dentistry. Nat Nanotechnol 5(8):565–569. https://doi.org/10.1038/nnano.2010.83

    Article  CAS  PubMed  Google Scholar 

  6. 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

    Article  CAS  Google Scholar 

  7. 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

    Article  CAS  PubMed  Google Scholar 

  8. 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

    Article  CAS  PubMed  Google Scholar 

  9. 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

    Article  CAS  PubMed  Google Scholar 

  10. 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

    Article  CAS  Google Scholar 

  11. 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

    Article  CAS  PubMed  Google Scholar 

  12. 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

    Article  CAS  PubMed  Google Scholar 

  13. 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

    Article  CAS  Google Scholar 

  14. 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

    Article  CAS  PubMed  Google Scholar 

  15. 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

    Article  CAS  PubMed  Google Scholar 

  16. 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

    Article  CAS  Google Scholar 

  17. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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

    Article  Google Scholar 

  19. 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

    Article  CAS  Google Scholar 

  20. 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

    Article  CAS  PubMed  Google Scholar 

  21. 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

    Article  CAS  PubMed  Google Scholar 

  22. 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

    Article  CAS  PubMed  Google Scholar 

  23. 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

    Article  CAS  PubMed  Google Scholar 

  24. 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

    Article  CAS  PubMed  Google Scholar 

  25. 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

    Article  CAS  Google Scholar 

  26. 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

    Article  CAS  PubMed  Google Scholar 

  27. 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

    Article  CAS  PubMed  Google Scholar 

  28. Skoryna SC (1981) Effects of oral supplementation with stable strontium. Can Med Assoc J 125(7):703–712

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 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

    Article  CAS  PubMed  Google Scholar 

  30. 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

    Article  CAS  Google Scholar 

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. 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

    Article  CAS  Google Scholar 

  33. 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

    Article  CAS  Google Scholar 

  34. 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

    Article  CAS  Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

  36. 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

    Article  CAS  PubMed  Google Scholar 

  37. 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

    Article  CAS  PubMed  Google Scholar 

  38. Anselme K (2000) Osteoblast adhesion on biomaterials. Biomaterials 21(7):667–681. https://doi.org/10.1016/s0142-9612(99)00242-2

    Article  CAS  PubMed  Google Scholar 

  39. 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

    Article  CAS  PubMed  Google Scholar 

  40. 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

    Article  CAS  PubMed  Google Scholar 

  41. 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

    Article  CAS  Google Scholar 

  42. 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

    Article  CAS  Google Scholar 

  43. 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

    Article  CAS  Google Scholar 

  44. 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

    Article  CAS  PubMed  Google Scholar 

  45. 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

    Article  CAS  PubMed  Google Scholar 

  46. 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

    Article  CAS  PubMed  Google Scholar 

  47. 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

    Article  CAS  PubMed  Google Scholar 

  48. 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

    Article  CAS  Google Scholar 

  49. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

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).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yingchun Zhu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-017-1226-5

Keywords

Navigation