Abstract
Calcium silicate cements have been considered as alternative bone substitutes owing to its extraordinary bioactivity and osteogenicity. Unfortunately, the major disadvantage of the cements was the slow degradation rate which may limit the efficiency of bone regeneration. In this study, we proposed a facile method to synthesize degradable calcium silicate cements by incorporating strontium into the cements through solid-state sintering. The effects of Sr incorporation on physicochemical and biological properties of the cements were evaluated. Although, our findings revealed that the incorporation of strontium retarded the hardening reaction of the cements, the setting time of different cements (11–19 min) were in the acceptable range for clinical use. The presence of Sr in the CS cements would hampered the precipitation of calcium phosphate products on the surface after immersion in SBF, however, a layer of precipitated calcium phosphate products can be formed on the surface of the Sr-CS cement within 1 day immersion in SBF. More importantly, the degradation rate of the cements increased with increasing content of strontium, consequentially raised the levels of released strontium and silicon ions. The elevated dissolving products may contribute to the enhancement of the cytocompatibility, alkaline phosphatase activity, osteocalcin secretion, and mineralization of human Wharton’s jelly mesenchymal stem cells. Together, it is concluded that the strontium-incorporated calcium silicate cement might be a promising bone substitute that could accelerate the regeneration of irregularly shaped bone defects.
Similar content being viewed by others
References
Shen X, Ma P, Hu Y, Xu G, Xu K, Chen W, et al. Alendronate-loaded hydroxyapatite-TiO2 nanotubes for improved bone formation in osteoporotic rabbits. J Mater Chem B. 2016;4:1423–36.
Huang MH, Kao CT, Chen YW, Hsu TT, Shieh DE, Huang TH, Shie MY. The synergistic effects of chinese herb and injectable calcium silicate/β-tricalcium phosphate composite on an osteogenic accelerator in vitro. J Mater Sci: Mater Med. 2015;26:161.
Jung GY, Park YJ, Han JS. Effects of HA released calcium ion on osteoblast differentiation. J Mater Sci: Mater Med. 2010;21:1649–54.
Bonnelye E, Chabadel A, Saltel F, Jurdic P. Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone. 2008;42:129–38.
Boanini E, Torricelli P, Gazzano M, Bella Della E, Fini M, Bigi A. Combined effect of strontium and zoledronate on hydroxyapatite structure and bone cell responses. Biomaterials. 2014;35:5619–26.
Zhang L, Huang X, Han Y. Formation mechanism and cytocompatibility of nano-shaped calcium silicate hydrate/calcium titanium silicate/TiO2 composite coatings on titanium. J Mater Chem B. 2016;4:6734–45.
Costa F, Sousa Gomes P, Fernandes MH. Osteogenic and angiogenic response to calcium silicate-based endodontic sealers. J Endod. 2016;42:113–9.
Chen YW, Hsu TT, Wang K, Shie MY. Preparation of the fast setting and degrading Ca-Si-Mg cement with both odontogenesis and angiogenesis differentiation of human periodontal ligament cells. Mater Sci Eng C Mater Biol Appl. 2016;60:374–83.
Chen YW, Ho CC, Huang TH, Hsu TT, Shie MY. The ionic products from mineral trioxide aggregate–induced odontogenic differentiation of dental pulp cells via activation of the Wnt/β-catenin signaling pathway. J Endod. 2016;42:1062–9.
Yoldaş SE, Bani M, Atabek D, Bodur H. Comparison of the potential discoloration effect of bioaggregate, biodentine, and white mineral trioxide aggregate on bovine teeth: in vitro research. J Endod. 2016;42:1815–8.
Chen YW, Yeh CH, Shie MY. Stimulatory effects of the fast setting and degradable Ca–Si–Mg cement on both cementogenesis and angiogenesis differentiation of human periodontal ligament cells. J Mater Chem B. 2015;3:7099–108.
Huang MH, Shen YF, Hsu TT, Huang TH, Shie MY. Physical characteristics, antimicrobial and odontogenesis potentials of calcium silicate cement containing hinokitiol. Mater Sci Eng C Mater Biol Appl. 2016;65:1–8.
Bellucci D, Sola A, Anesi A, Salvatori R, Chiarini L, Cannillo V. Bioactive glass/hydroxyapatite composites: mechanical properties and biological evaluation. Mater Sci Eng C Mater Biol Appl. 2015;51:196–205.
Kao CT, Huang TH, Chen YJ, Hung CJ, Lin CC, Shie MY. Using calcium silicate to regulate the physicochemical and biological properties when using β-tricalcium phosphate as bone cement. Mater Sci Eng C Mater Biol Appl. 2014;43:126–34.
Zhang W, Zhao F, Huang D, Fu X, Li X, Chen X. Strontium-substituted submicrometer bioactive glasses modulate macrophage responses for improved bone regeneration. ACS Appl Mater Interfaces. 2016;8:30747–58.
John Ł, Podgórska M, Nedelec JM, Cwynar-Zając Ł, Dzięgiel P. Strontium-doped organic-inorganic hybrids towards three-dimensional scaffolds for osteogenic cells. Mater Sci Eng C Mater Biol Appl. 2016;68:117–27.
Zhu H, Zhai D, Lin C, Zhang Y, Huan Z, Chang J, Wu C. 3D plotting of highly uniform Sr5(PO4)2SiO4 bioceramic scaffolds for bone tissue engineering. J Mater Chem B. 2016;4:6200–12.
Zhang Y, Wei L, Chang J, Miron RJ, Shi B, Yi S, Wu C. Strontium-incorporated mesoporous bioactive glass scaffolds stimulating in vitro proliferation and differentiation of bone marrow stromal cells and in vivo regeneration of osteoporotic bone defects. J Mater Chem B. 2013;1:5711–22.
Zhang Y, Cui X, Zhao S, Wang HC, Rahaman MN, Liu Z, et al. Evaluation of injectable strontium-containing borate bioactive glass cement with enhanced osteogenic capacity in a critical-sized rabbit femoral condyle defect model. ACS Appl Mater Interfaces. 2015;7:2393–403.
Huang CY, Huang TH, Kao CT, Wu YH, Chen WC, Shie MY. Mesoporous calcium silicate nanoparticles with drug delivery and odontogenesis properties. J Endod. 2017;43:69–76.
Cheng YL, Chen YW, Wang K, Shie MY. Enhanced adhesion and differentiation of human mesenchymal stem cell inside apatite-mineralized/poly(dopamine)-coated poly(ε-caprolactone) scaffolds by stereolithography. J Mater Chem B. 2016;4:6307–15.
Lin K, Xia L, Li H, Jiang X, Pan H, Xu Y, et al. Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics. Biomaterials. 2013;34:10028–42.
Gou Z, Chang J, Zhai W, Wang J. Study on the self-setting property and the in vitro bioactivity of beta-Ca2SiO4. J Biomed Mater Res B Appl Biomater. 2005;73:244–51.
Gupta SK, Nigam S, Yadav AK, Mohapatra M, Jha SN, Majumder C, et al. An insight into local environment of lanthanide ions in Sr2SiO4:Ln (Ln = Sm, Eu and Dy). New J Chem. 2015;39:6531–9.
Zhang J, Qiu Y, Huang M, Zheng H, Yanagisawa K. Accelerated formation of strontium silicate by solid-state reaction in NaCl–H2O(v) system at lower temperature. Appl Surf Sci. 2015;347:57–63.
Zhang Z, Scherer GW, Bauer A. Morphology of cementitious material during early hydration. Cem Concr Res. 2018;107:85–100.
Reginster JY, Lecart MP, Deroisy R, Lousberg C. Strontium ranelate: a new paradigm in the treatment of osteoporosis. Expert Opin Investig Drugs. 2004;13:857–64.
Reid IR. Short-term and long-term effects of osteoporosis therapies. Nat Rev Endocrinol. 2015;11:418–28.
Fernández E, Gil FJ, Ginebra MP, Driessens FC, Planell JA, Best SM. Production and characterization of new calcium phosphate bone cements in the CaHPO4-alpha-Ca3(PO4)2 system: pH, workability and setting times. J Mater Sci Mater Med. 1999;10:223–30.
Garrault S, Nonat A. Hydrated layer formation on tricalcium and dicalcium silicate surfaces: Experimental study and numerical simulations. Langmuir. 2001;17:8131–8.
Tits J, Wieland E, Müller CJ, Landesman C, Bradbury MH. Strontium binding by calcium silicate hydrates. J Colloid Interface Sci. 2006;300:78–87.
Liu X, Ding C, Chu PK. Mechanism of apatite formation on wollastonite coatings in simulated body fluids. Biomaterials. 2004;25:1755–61.
Wu C, Ramaswamy Y, Kwik D, Zreiqat H. The effect of strontium incorporation into CaSiO3 ceramics on their physical and biological properties. Biomaterials. 2007;28:3171–81.
Fujikura K, Karpukhina N, Kasuga T, Brauer DS, Hill RG, Law RV. Influence of strontium substitution on structure and crystallisation of Bioglass® 45S5. J Mater Chem. 2012;22:7395–402.
Lao J, Nedelec JM, Jallot E. New strontium-based bioactive glasses: physicochemical reactivity and delivering capability of biologically active dissolution products. J Mater Chem. 2009;19:2940–9.
Gómez-Leduc T, Desancé M, Hervieu M, Legendre F, Ollitrault D, de Vienne C, et al. Hypoxia is a critical parameter for chondrogenic differentiation of human umbilical cord blood mesenchymal stem cells in type I/III collagen sponges. Int J Mol Sci. 2017;18:1933.
Choe G, Park J, Park H, Lee JY. Hydrogel biomaterials for stem cell microencapsulation. Polymers. 2018;10:997.
Fong CY, Chak LL, Biswas A, Tan JH, Gauthaman K, Chan WK, Bongso A. Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev. 2011;7:1–16.
No YJ, Li JJ, Zreiqat H. Doped calcium silicate ceramics: a new class of candidates for synthetic bone substitutes. Materials. 2017;10:53.
Han P, Wu C, Xiao Y. The effect of silicate ions on proliferation, osteogenic differentiation and cell signalling pathways (WNT and SHH) of bone marrow stromal cells. Biomater Sci. 2013;1:379–92.
Shie MY, Ding SJ, Chang HC. The role of silicon in osteoblast-like cell proliferation and apoptosis. Acta Biomater. 2011;7:2604–14.
Kao CT, Chen YJ, Ng HY, Lee AK, Huang TH, Lin TF, Hsu TT. Surface modification of calcium silicate via mussel-inspired polydopamine and effective adsorption of extracellular matrix to promote osteogenesis differentiation for bone tissue engineering. Materials. 2018;11:1664.
Acknowledgements
The authors acknowledge receipt grants from the Ministry of Science and Technology (MOST 106-2314-B-040-003-MY3), China Medical University Hospital grants (DMR-107-150), and Chung Shan Medical University Hospital grants (CSH-2019-039).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
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
Huang, TH., Kao, CT., Shen, YF. et al. Substitutions of strontium in bioactive calcium silicate bone cements stimulate osteogenic differentiation in human mesenchymal stem cells. J Mater Sci: Mater Med 30, 68 (2019). https://doi.org/10.1007/s10856-019-6274-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10856-019-6274-2