The osteogenic response of mesenchymal stromal cells to strontium‐substituted bioactive glasses

Bioactive glasses are known to stimulate bone healing, and the incorporation of strontium has the potential to increase their potency. In this study, calcium oxide in the 45S5 bioactive glass composition was partially (50%, Sr50) or fully (100%, Sr100) substituted with strontium oxide on a molar basis. The effects of the substitution on bioactive glass properties were studied, including density, solubility, and in vitro cytotoxicity. Stimulation of osteogenic differentiation was investigated using mesenchymal stromal cells obtained from rat bone marrow. Strontium substitution resulted in altered physical properties including increased solubility. Statistically significant reductions in cell viability were observed with the addition of bioactive glass powders to culture medium. Specifically, addition of ≥ 13.3 mg/ml of 45S5 bioactive glass or Sr50, or ≥ 6.7 mg/ml of Sr100, resulted in significant inhibition. Real‐time PCR analyses detected the upregulation of genes associated with osteoblastic differentiation in the presence of all bioactive glass compositions. Some genes, including Alpl and Bglap, were further stimulated in the presence of Sr50 and Sr100. It was concluded that strontium‐substituted bioactive glasses promoted osteogenesis in a differentiating bone cell culture model and, therefore, have considerable potential for use as improved bioactive glasses for bone tissue regeneration. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.

[1]  Chengtie Wu,et al.  Periodontal Regeneration Using Strontium-Loaded Mesoporous Bioactive Glass Scaffolds in Osteoporotic Rats , 2014, PloS one.

[2]  P. Marie Strontium as therapy for osteoporosis. , 2005, Current opinion in pharmacology.

[3]  Gavin Jell,et al.  The effects of strontium-substituted bioactive glasses on osteoblasts and osteoclasts in vitro. , 2010, Biomaterials.

[4]  J. Polak,et al.  Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. , 2000, Biochemical and biophysical research communications.

[5]  A. Boccaccini,et al.  Adipose‐ and bone marrow‐derived mesenchymal stem cells display different osteogenic differentiation patterns in 3D bioactive glass‐based scaffolds , 2016, Journal of tissue engineering and regenerative medicine.

[6]  Aldo R Boccaccini,et al.  A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. , 2011, Biomaterials.

[7]  C. Maniatopoulos,et al.  Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats , 1988, Cell and Tissue Research.

[8]  L L Hench,et al.  Gene-expression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. , 2001, Journal of biomedical materials research.

[9]  Larry L. Hench,et al.  The story of Bioglass® , 2006, Journal of materials science. Materials in medicine.

[10]  G. Reilly,et al.  Differential alkaline phosphatase responses of rat and human bone marrow derived mesenchymal stem cells to 45S5 bioactive glass. , 2007, Biomaterials.

[11]  M. Bosetti,et al.  The effect of bioactive glasses on bone marrow stromal cells differentiation. , 2005, Biomaterials.

[12]  Larry L. Hench,et al.  Crystallization kinetics of tape cast bioactive glass 45S5 , 2003 .

[13]  Jun-Ying Sun,et al.  The effect of the ionic products of Bioglass® dissolution on human osteoblasts growth cycle in vitro , 2007, Journal of tissue engineering and regenerative medicine.

[14]  J. Nedelec,et al.  Strontium-Delivering Glasses with Enhanced Bioactivity: A New Biomaterial for Antiosteoporotic Applications? , 2008 .

[15]  P. Marie,et al.  Transcription factors controlling osteoblastogenesis. , 2008, Archives of biochemistry and biophysics.

[16]  W. Stark,et al.  Novel strontium-doped bioactive glass nanoparticles enhance proliferation and osteogenic differentiation of human bone marrow stromal cells , 2013, Journal of Nanoparticle Research.

[17]  E. Brown,et al.  The Calcium-sensing Receptor Is Involved in Strontium Ranelate-induced Osteoclast Apoptosis , 2009, Journal of Biological Chemistry.

[18]  Julian R Jones,et al.  Review of bioactive glass: from Hench to hybrids. , 2013, Acta biomaterialia.

[19]  A. Berdal,et al.  Effects of strontium-doped bioactive glass on the differentiation of cultured osteogenic cells. , 2011, European cells & materials.

[20]  A. Feki,et al.  The potential restorative effects of strontium-doped bioactive glass on bone microarchitecture after estrogen-deficieny induced osteoporosis: Physicochemical and histomorphometric analyses , 2013, Journal of the Korean Society for Applied Biological Chemistry.

[21]  G. Cuniberti,et al.  Bioactive SrO-SiO2 glass with well-ordered mesopores: characterization, physiochemistry and biological properties. , 2011, Acta biomaterialia.

[22]  H. Doweidar The density of alkali silicate glasses in relation to the microstructure , 1996 .

[23]  P. Hatton,et al.  Influence of sodium oxide content on bioactive glass properties , 1999, Journal of materials science. Materials in medicine.

[24]  H. Doweidar Density-structure correlations in silicate glasses , 1999 .

[25]  C. Rey,et al.  Mechanisms of Action and Therapeutic Potential of Strontium in Bone , 2001, Calcified Tissue International.

[26]  P. Marie,et al.  Strontium signaling: molecular mechanisms and therapeutic implications in osteoporosis. , 2012, Pharmacology & therapeutics.

[27]  R. Cabrini,et al.  Osteoconductivity of strontium-doped bioactive glass particles: a histomorphometric study in rats. , 2010, Journal of biomedical materials research. Part A.

[28]  Lintao Cai,et al.  Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling , 2011, Stem cells.

[29]  P. Marie Strontium ranelate: New insights into its dual mode of action , 2007 .

[30]  M. Barbe,et al.  Bone Structure, Development and Bone Biology , 2009 .

[31]  I. Prasadam,et al.  A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects , 2014, Osteoporosis International.

[32]  J. Nedelec,et al.  New strontium-based bioactive glasses: physicochemical reactivity and delivering capability of biologically active dissolution products , 2009 .

[33]  F. Saltel,et al.  Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. , 2008, Bone.

[34]  Robert V. Law,et al.  Strontium containing bioactive glasses: Glass structure and physical properties , 2010 .

[35]  K. Luk,et al.  Strontium Promotes Osteogenic Differentiation of Mesenchymal Stem Cells Through the Ras/MAPK Signaling Pathway , 2009, Cellular Physiology and Biochemistry.

[36]  G. Reilly,et al.  Osteogenic effects of bioactive glass on bone marrow stromal cells. , 2005, Journal of biomedical materials research. Part A.

[37]  J. Schrooten,et al.  A calcium-induced signaling cascade leading to osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells. , 2012, Biomaterials.

[38]  Larry L. Hench,et al.  Bioglass ®45S5 Stimulates Osteoblast Turnover and Enhances Bone Formation In Vitro: Implications and Applications for Bone Tissue Engineering , 2000, Calcified Tissue International.

[39]  Julian R. Jones,et al.  Differentiation of fetal osteoblasts and formation of mineralized bone nodules by 45S5 Bioglass conditioned medium in the absence of osteogenic supplements. , 2009, Biomaterials.

[40]  Julian R. Jones,et al.  Monodispersed Bioactive Glass Submicron Particles and Their Effect on Bone Marrow and Adipose Tissue‐Derived Stem Cells , 2014, Advanced healthcare materials.

[41]  G. Cuniberti,et al.  Bioactive SrO-SiO 2 glass with well-ordered mesopores: characterization, physiochemistry and biological properties , 2011 .

[42]  Changqing Zhang,et al.  Evaluation of the proliferation and differentiation behaviors of mesenchymal stem cells with partially converted borate glass containing different amounts of strontium in vitro. , 2013, Molecular medicine reports.

[43]  Carl Miller,et al.  Materials characterisation and cytotoxic assessment of strontium-substituted bioactive glasses for bone regeneration , 2010 .