Biocompatibility property of 100% strontium-substituted SiO2 -Al2 O3 -P2 O5 -CaO-CaF2 glass ceramics over 26 weeks implantation in rabbit model: Histology and micro-Computed Tomography analysis.

One of the desired properties for any new biomaterial composition is its long-term stability in a suitable animal model and such property cannot be appropriately assessed by performing short-term implantation studies. While hydroxyapatite (HA) or bioglass coated metallic biomaterials are being investigated for in vivo biocompatibility properties, such study is not extensively being pursued for bulk glass ceramics. In view of their inherent brittle nature, the implant stability as well as impact of long-term release of metallic ions on bone regeneration have been a major concern. In this perspective, the present article reports the results of the in vivo implantation experiments carried out using 100% strontium (Sr)-substituted glass ceramics with the nominal composition of 4.5 SiO2 -3Al2 O3 -1.5P2 O5 -3SrO-2SrF2 for 26 weeks in cylindrical bone defects in rabbit model. The combination of histological and micro-computed tomography analysis provided a qualitative and quantitative understanding of the bone regeneration around the glass ceramic implants in comparison to the highly bioactive HA bioglass implants (control). The sequential polychrome labeling of bone during in vivo osseointegration using three fluorochromes followed by fluorescence microscopy observation confirmed homogeneous bone formation around the test implants. The results of the present study unequivocally confirm the long-term implant stability as well as osteoconductive property of 100% Sr-substituted glass ceramics, which is comparable to that of a known bioactive implant, that is, HA-based bioglass.

[1]  T. Kokubu,et al.  SEM-EPMA observation of three types of apatite-containing glass-ceramics implanted in bone: the variance of a Ca-P-rich layer. , 1987, Journal of biomedical materials research.

[2]  C. Christiansen,et al.  Incorporation and distribution of strontium in bone. , 2001, Bone.

[3]  L. Brentegani,et al.  Histological evaluation of the biocompatibility of a glass-ionomer cement in rat alveolus. , 1997, Biomaterials.

[4]  P Ducheyne,et al.  Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. , 1999, Biomaterials.

[5]  F. Kloss,et al.  Accelerated bone ingrowth by local delivery of strontium from surface functionalized titanium implants. , 2013, Biomaterials.

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

[7]  M. Baslé,et al.  Cellular response to calcium phosphate ceramics implanted in rabbit bone , 1993 .

[8]  P. Chappuis,et al.  Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis). , 2001, Bone.

[9]  B. Blenckè.  Compatibility and long-term stability of glass-ceramic implants. , 1978, Journal of biomedical materials research.

[10]  O. Fromigué,et al.  Calcium sensing receptor‐dependent and receptor‐independent activation of osteoblast replication and survival by strontium ranelate , 2009 .

[11]  Jun Yan,et al.  Porous Allograft Bone Scaffolds: Doping with Strontium , 2013, PloS one.

[12]  H. Varma,et al.  Can Iliac Crest Reconstruction Reduce Donor Site Morbidity?: A Study Using Degradable Hydroxyapatite-bioactive Glass Ceramic Composite , 2010, Journal of spinal disorders & techniques.

[13]  C. Grobbelaar,et al.  Biological evaluation of glass-ionomer cement (Ketac-0) as an interface material in total joint replacement. A screening test , 1989 .

[14]  C. Davidson.  Advances in glass-ionomer cements. , 2006, Journal of applied oral science : revista FOB.

[15]  D. Williams,et al.  Biocompatibility of glass ionomer cements. , 1993, Biomaterials.

[16]  C. Knabe,et al.  Development of multinuclear giant cells during the degradation of Bioglass particles in rabbits. , 2004, Journal of biomedical materials research. Part A.

[17]  S. Mcloughlin,et al.  Differential healing response of bone adjacent to porous implants coated with hydroxyapatite and 45S5 bioactive glass. , 2001, Journal of biomedical materials research.

[18]  W. Vogel,et al.  Interface reactions between machinable bioactive glass-ceramics and bone. , 1985, Journal of biomedical materials research.

[19]  M. Buggy,et al.  Bone cements and fillers: A review , 2003, Journal of materials science. Materials in medicine.

[20]  H. Varma,et al.  Treatment of goat femur segmental defects with silica-coated hydroxyapatite--one-year follow-up. , 2010, Tissue engineering. Part A.

[21]  S. Friedman,et al.  Evaluation of success and failure after endodontic therapy using a glass ionomer cement sealer. , 1995, Journal of endodontics.

[22]  D. Boyd,et al.  An investigation into the structure and reactivity of calcium-zinc-silicate ionomer glasses using MAS-NMR spectroscopy , 2006, Journal of materials science. Materials in medicine.

[23]  H. Varma,et al.  A triphasic ceramic-coated porous hydroxyapatite for tissue engineering application. , 2008, Acta biomaterialia.

[24]  W. Lu,et al.  Interfacial behaviour of strontium-containing hydroxyapatite cement with cancellous and cortical bone. , 2006, Biomaterials.

[25]  P. Hatton,et al.  Glass-ionomers: bioactive implant materials. , 1998, Biomaterials.

[26]  D. Wood,et al.  Influence of Fluorine Content in Apatite–Mullite Glass‐Ceramics , 2004 .

[27]  Stefan Milz,et al.  Polychrome labeling of bone with seven different fluorochromes: enhancing fluorochrome discrimination by spectral image analysis. , 2005, Bone.

[28]  P. Lehenkari,et al.  Bone modeling and cell-material interface responses induced by nickel-titanium shape memory alloy after periosteal implantation. , 1999, Biomaterials.

[29]  B. Basu,et al.  Early osseointegration of a strontium containing glass ceramic in a rabbit model. , 2013, Biomaterials.

[30]  Sumio Sakka,et al.  Formation of a high-strength bioactive glass-ceramic in the system MgO-CaO-SiO2-P2O5 , 1986 .

[31]  I. Brook,et al.  Bone cell interactions with a granular glass-ionomer bone substitute material: in vivo and in vitro culture models. , 1992, Biomaterials.

[32]  M. Towler,et al.  The influence of strontium substitution in fluorapatite glasses and glass-ceramics , 2004 .

[33]  P. Marie,et al.  The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro. , 1996, Bone.

[34]  T. Kumar,et al.  Strontium‐Substituted Calcium Deficient Hydroxyapatite Nanoparticles: Synthesis, Characterization, and Antibacterial Properties , 2012 .

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

[36]  Yann C. Fredholm,et al.  Structural analysis of a series of strontium-substituted apatites. , 2008, Acta biomaterialia.

[37]  R. Hill,et al.  Real‐Time Nucleation and Crystallization Studies of a Fluorapatite Glass–Ceramics Using Small‐Angle Neutron Scattering and Neutron Diffraction , 2007 .

[38]  Raghu Raman Rajagopal,et al.  Influence of strontium on structure, sintering and biodegradation behaviour of CaO-MgO-SrO-SiO(2)-P(2)O(5)-CaF(2) glasses. , 2011, Acta biomaterialia.

[39]  R van Noort,et al.  In vivo bone tissue response to a canasite glass-ceramic. , 2002, Biomaterials.

[40]  M. Rybchyn,et al.  Osteoblasts play key roles in the mechanisms of action of strontium ranelate , 2009, British journal of pharmacology.

[41]  I. Brook,et al.  Bone response to a titanium aluminium nitride coating on metallic implants , 2006, Journal of materials science. Materials in medicine.

[42]  David J Mooney,et al.  Quantitative assessment of scaffold and growth factor‐mediated repair of critically sized bone defects , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[43]  A. Guida,et al.  Preliminary work on the antibacterial effect of strontium in glass ionomer cements , 2003 .