A bioceramic with enhanced osteogenic properties to regulate the function of osteoblastic and osteocalastic cells for bone tissue regeneration

Bioceramics for regenerative medicine applications should have the ability to promote adhesion, proliferation and differentiation of osteoblast and osteoclast cells. Osteogenic properties of the material are essential for rapid bone regeneration and new bone formation. The aim of this study was to develop a silicate-based ceramic, gehlenite (GLN, Ca2Al2SiO7), and characterise its physiochemical, biocompatibility and osteogenic properties. A pure GLN powder was synthesised by a facile reactive sintering method and compacted to disc-shaped specimens. The sintering behaviour and degradation of the GLN discs in various buffer solutions were fully characterised. The cytotoxicity of GLN was evaluated by direct and indirect methods. In the indirect method, primary human osteoblast cells (HOBs) were exposed to diluted extracts (100, 50, 25, 12.5 and 6.25 mg ml−1) of fine GLN particles in culture medium. The results showed that the extracts did not cause any cytotoxic effect on the HOBs with the number of cells increasing significantly from day 1 to day 7. GLN-supported HOB attachment and proliferation, and significantly enhanced osteogenic gene expression levels (Runx2, osteocalcin, osteopontin and bone sialoprotein) were compared with biphasic calcium phosphate groups (BCP, a mixture of hydroxyapatite (60wt.%) and β-tricalcium phosphate(40wt.%)). We also demonstrated that in addition to supporting HOB attachment and proliferation, GLN promoted the formation of tartrate-acid resistance phosphatase (TRAP) positive multinucleated osteoclastic cells (OCs) derived from mouse bone marrow cells. Results also demonstrated the ability of GLN to support the polarisation of OCs, a prerequisite for their functional resorptive activity which is mainly influenced by the composition and degradability of biomaterials. Overall, the developed GLN is a prospective candidate to be used in bone regeneration applications due its effective osteogenic properties and biocompatibility.

[1]  Daniel A. Grande,et al.  The current state of scaffolds for musculoskeletal regenerative applications , 2015, Nature Reviews Rheumatology.

[2]  W. Walsh,et al.  The Masquelet Technique for Membrane Induction and the Healing of Ovine Critical Sized Segmental Defects , 2014, PloS one.

[3]  G. Calori,et al.  Incidence of donor site morbidity following harvesting from iliac crest or RIA graft. , 2014, Injury.

[4]  G. Pei,et al.  Efficacy of prevascularization for segmental bone defect repair using β-tricalcium phosphate scaffold in rhesus monkey. , 2014, Biomaterials.

[5]  G. Logroscino,et al.  Bone substitutes in orthopaedic surgery: from basic science to clinical practice , 2014, Journal of Materials Science: Materials in Medicine.

[6]  J. Planell,et al.  Angiogenesis in bone regeneration: tailored calcium release in hybrid fibrous scaffolds. , 2014, ACS applied materials & interfaces.

[7]  S. Hampshire,et al.  Bioactivity potential of calcium alumino-silicate glasses and glass–ceramics containing nitrogen and fluorine , 2014, Journal of Materials Science.

[8]  H. Zreiqat,et al.  Fabrication of a novel triphasic and bioactive ceramic and evaluation of its in vitro and in vivo cytocompatibility and osteogenesis. , 2014, Journal of materials chemistry. B.

[9]  A. Teti Mechanisms of osteoclast-dependent bone formation. , 2013, BoneKEy reports.

[10]  J. Havlica,et al.  Kinetics and mechanism of formation of gehlenite, Al–Si spinel and anorthite from the mixture of kaolinite and calcite , 2013 .

[11]  Guoping Chen,et al.  Stimulatory effects of the ionic products from Ca-Mg-Si bioceramics on both osteogenesis and angiogenesis in vitro. , 2013, Acta biomaterialia.

[12]  Teja Guda,et al.  Development of Composite Scaffolds for Load-Bearing Segmental Bone Defects , 2013, BioMed research international.

[13]  Larry L. Hench,et al.  An Introduction to Bioceramics , 2013 .

[14]  H. Kim,et al.  Bone formation controlled by biologically relevant inorganic ions: role and controlled delivery from phosphate-based glasses. , 2013, Advanced drug delivery reviews.

[15]  Haiyan Li,et al.  Bioactive silicate materials stimulate angiogenesis in fibroblast and endothelial cell co-culture system through paracrine effect. , 2013, Acta biomaterialia.

[16]  Shengmin Zhang,et al.  Osteogenic differentiation of bone marrow mesenchymal stem cells on the collagen/silk fibroin bi-template-induced biomimetic bone substitutes. , 2012, Journal of biomedical materials research. Part A.

[17]  Yanfei Han,et al.  Aluminum Induces Osteoblast Apoptosis Through the Oxidative Stress-Mediated JNK Signaling Pathway , 2012, Biological Trace Element Research.

[18]  D. Hutmacher,et al.  A Tissue Engineering Solution for Segmental Defect Regeneration in Load-Bearing Long Bones , 2012, Science Translational Medicine.

[19]  Changsheng Liu,et al.  Segmental bone regeneration using rhBMP-2-loaded collagen/chitosan microspheres composite scaffold in a rabbit model , 2012, Biomedical materials.

[20]  Serena M Best,et al.  Substituted hydroxyapatites for bone repair , 2012, Journal of Materials Science: Materials in Medicine.

[21]  María Vallet-Regí,et al.  Bioceramics: From Bone Regeneration to Cancer Nanomedicine , 2011, Advanced materials.

[22]  Y. Sogo,et al.  Synthesis and characterization of hierarchically macroporous and mesoporous CaO-MO-SiO(2)-P(2)O(5) (M=Mg, Zn, Sr) bioactive glass scaffolds. , 2011, Acta biomaterialia.

[23]  J. Barralet,et al.  Bioinorganics and biomaterials: bone repair. , 2011, Acta biomaterialia.

[24]  Jochen Eulert,et al.  Custom-made composite scaffolds for segmental defect repair in long bones , 2011, International Orthopaedics.

[25]  Rozalia Dimitriou,et al.  Bone regeneration: current concepts and future directions , 2011, BMC medicine.

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

[27]  Erica L. Corral,et al.  Toughening in graphene ceramic composites. , 2011, ACS nano.

[28]  D. Boyd,et al.  The effect of ionic dissolution products of Ca–Sr–Na–Zn–Si bioactive glass on in vitro cytocompatibility , 2010, Journal of materials science. Materials in medicine.

[29]  B. Basu,et al.  In vitro dissolution of calcium phosphate-mullite composite in simulated body fluid , 2010, Journal of materials science. Materials in medicine.

[30]  Hala Zreiqat,et al.  The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering. , 2010, Biomaterials.

[31]  M. Bohner Silicon-substituted calcium phosphates - a critical view. , 2009, Biomaterials.

[32]  B. Basu,et al.  In vivo response of novel calcium phosphate-mullite composites: results up to 12 weeks of implantation. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[33]  A. Mukhopadhyay,et al.  Nanoindentation response of novel hydroxyapatite–mullite composites , 2009 .

[34]  Marco Wieland,et al.  Mechanisms regulating increased production of osteoprotegerin by osteoblasts cultured on microstructured titanium surfaces. , 2009, Biomaterials.

[35]  Chengtie Wu,et al.  The responses of osteoblasts, osteoclasts and endothelial cells to zirconium modified calcium-silicate-based ceramic. , 2008, Biomaterials.

[36]  D. Jia,et al.  Sintering Behavior of Gehlenite, Part II. Microstructure and Mechanical Properties , 2007 .

[37]  D W Hutmacher,et al.  A comparative analysis of scaffold material modifications for load-bearing applications in bone tissue engineering. , 2006, International journal of oral and maxillofacial surgery.

[38]  V. Barranco,et al.  Concentration-dependent effects of titanium and aluminium ions released from thermally oxidized Ti6Al4V alloy on human osteoblasts. , 2006, Journal of biomedical materials research. Part A.

[39]  H. Zreiqat,et al.  Bioceramics composition modulate resorption of human osteoclasts , 2005, Journal of materials science. Materials in medicine.

[40]  S Wenisch,et al.  In vivo mechanisms of hydroxyapatite ceramic degradation by osteoclasts: fine structural microscopy. , 2003, Journal of biomedical materials research. Part A.

[41]  Masakazu Kawashita,et al.  Novel bioactive materials with different mechanical properties. , 2003, Biomaterials.

[42]  L. Canham,et al.  Silicon: the evolution of its use in biomaterials. , 2015, Acta biomaterialia.

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

[44]  Guoping Chen,et al.  Silicate bioceramics induce angiogenesis during bone regeneration. , 2012, Acta biomaterialia.

[45]  Amy J Wagoner Johnson,et al.  A review of the mechanical behavior of CaP and CaP/polymer composites for applications in bone replacement and repair. , 2011, Acta biomaterialia.

[46]  Si-yu Ni,et al.  In vitro studies of novel CaO–SiO2–MgO system composite bioceramics , 2008, Journal of materials science. Materials in medicine.

[47]  J. Déjou,et al.  The biodegradation mechanism of calcium phosphate biomaterials in bone. , 2002, Journal of biomedical materials research.

[48]  Theo Fett,et al.  Ceramics: Mechanical Properties, Failure Behaviour, Materials Selection , 1999 .