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      Novel bioglasses for bone tissue repair and regeneration: Effect of glass design on sintering ability, ion release and biocompatibility

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          Abstract

          Eight novel silicate, phosphate and borate glass compositions (coded as NCLx, where x = 1 to 8), containing different oxides ( i.e. MgO, MnO 2, Al 2O 3, CaF 2, Fe 2O 3, ZnO, CuO, Cr 2O 3) were designed and evaluated alongside apatite-wollastonite (used as comparison material), as potential biomaterials for bone tissue repair and regeneration. Glass frits of all the formulations were processed to have particle sizes under 53 μm, with their morphology and dimensions subsequently investigated by scanning electron microscopy (SEM). In order to establish the nature of the raw glass powders, X-ray diffraction (XRD) analysis was also performed. The sintering ability of the novel materials was determined by using hot stage microscopy (HSM). Ionic release potential was assessed by inductively coupled plasma optical emission spectroscopy (ICP-OES). Finally, the cytotoxic effect of the novel glass powders was evaluated for different glass concentrations via a colorimetric assay, on which basis three formulations are considered promising biomaterials.

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          Highlights

          • Eight novel bioglass compositions based on silicate, phosphate and borate network formers have been investigated;

          • The glass forming ability of the formulations was composition dependent;

          • HSM proved an effective method to obtain accurate information about the thermal behaviour of the novel formulations;

          • Three formulations are considered to show promise for future application as musculoskeletal biomaterials.

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          Most cited references71

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          A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics.

          Several inorganic materials such as special compositions of silicate glasses, glass-ceramics and calcium phosphates have been shown to be bioactive and resorbable and to exhibit appropriate mechanical properties which make them suitable for bone tissue engineering applications. However, the exact mechanism of interaction between the ionic dissolution products of such inorganic materials and human cells are not fully understood, which has prompted considerable research work in the biomaterials community during the last decade. This review comprehensively covers literature reports which have investigated specifically the effect of dissolution products of silicate bioactive glasses and glass-ceramics in relation to osteogenesis and angiogenesis. Particularly, recent advances made in fabricating dense biomaterials and scaffolds doped with trace elements (e.g. Zn, Sr, Mg, and Cu) and investigations on the effect of these elements on the scaffold biological performance are summarized and discussed in detail. Clearly, the biological response to artificial materials depends on many parameters such as chemical composition, topography, porosity and grain size. This review, however, focuses only on the ion release kinetics of the materials and the specific effect of the released ionic dissolution products on human cell behaviour, providing also a scope for future investigations and identifying specific research needs to advance the field. The biological performance of pure and doped silicate glasses, phosphate based glasses with novel specific compositions as well as several other silicate based compounds are discussed in detail. Cells investigated in the reviewed articles include human osteoblastic and osteoclastic cells as well as endothelial cells and stem cells. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Novel bioactive materials with different mechanical properties.

            Some ceramics, such as Bioglass, sintered hydroxyapatite, and glass-ceramic A-W, spontaneously bond to living bone. They are called bioactive materials and are already clinically used as important bone substitutes. However, compared with human cortical bone, they have lower fracture toughness and higher elastic moduli. Therefore, it is desirable to develop bioactive materials with improved mechanical properties. All the bioactive materials mentioned above form a bone-like apatite layer on their surfaces in the living body, and bond to bone through this apatite layer. The formation of bone-like apatite on artificial material is induced by functional groups, such as Si-OH, Ti-OH, Zr-OH, Nb-OH, Ta-OH, -COOH, and PO(4)H(2). These groups have specific structures revealing negatively charge, and induce apatite formation via formations of an amorphous calcium compound, e.g., calcium silicate, calcium titanate, and amorphous calcium phosphate. These fundamental findings provide methods for preparing new bioactive materials with different mechanical properties. Tough bioactive materials can be prepared by the chemical treatment of metals and ceramics that have high fracture toughness, e.g., by the NaOH and heat treatments of titanium metal, titanium alloys, and tantalum metal, and by H(3)PO(4) treatment of tetragonal zirconia. Soft bioactive materials can be synthesized by the sol-gel process, in which the bioactive silica or titania is polymerized with a flexible polymer, such as polydimethylsiloxane or polytetramethyloxide, at the molecular level to form an inorganic-organic nano-hybrid. The biomimetic process has been used to deposit nano-sized bone-like apatite on fine polymer fibers, which were textured into a three-dimensional knit framework. This strategy is expected to ultimately lead to bioactive composites that have a bone-like structure and, hence, bone-like mechanical properties.
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              Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity.

              It is of great importance to develop multifunctional bioactive scaffolds, which combine angiogenesis capacity, osteostimulation, and antibacterial properties for regenerating lost bone tissues. In order to achieve this aim, we prepared copper (Cu)-containing mesoporous bioactive glass (Cu-MBG) scaffolds with interconnective large pores (several hundred micrometer) and well-ordered mesopore channels (around 5 nm). Both Cu-MBG scaffolds and their ionic extracts could stimulate hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression in human bone marrow stromal cells (hBMSCs). In addition, both Cu-MBG scaffolds and their ionic extracts significantly promoted the osteogenic differentiation of hBMSCs by improving their bone-related gene expression (alkaline phosphatase (ALP), osteopontin (OPN) and osteocalcin (OCN)). Furthermore, Cu-MBG scaffolds could maintain a sustained release of ibuprofen and significantly inhibited the viability of bacteria. This study indicates that the incorporation of Cu(2+) ions into MBG scaffolds significantly enhances hypoxia-like tissue reaction leading to the coupling of angiogenesis and osteogenesis. Cu(2+) ions play an important role to offer the multifunctional properties of MBG scaffold system. This study has demonstrated that it is possible to develop multifunctional scaffolds by combining enhanced angiogenesis potential, osteostimulation, and antibacterial properties for the treatment of large bone defects. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Mater Des
                Mater Des
                Materials & Design
                Scientific and Technical Press
                0264-1275
                05 September 2017
                05 September 2017
                : 129
                : 239-248
                Affiliations
                [a ]School of Mechanical and Systems Engineering, Newcastle University, UK
                [b ]School of Mechanical Engineering, University of Leeds, UK
                [c ]Glass Technology Services Ltd, Sheffield, UK
                [d ]Division of Trauma and Orthopaedic Surgery, University of Cambridge, UK
                Author notes
                [* ]Corresponding author at: School of Mechanical Engineering, University of Leeds, Woodhouse Lane, LS2 9JT Leeds, UK.School of Mechanical EngineeringUniversity of LeedsWoodhouse LaneLeedsLS2 9JTUK e.mancuso@ 123456leeds.ac.uk
                Article
                S0264-1275(17)30518-X
                10.1016/j.matdes.2017.05.037
                5521854
                28883669
                1e29b97e-e1f1-4c50-8a29-521daa31a39b
                © 2017 The Authors. Published by Elsevier Ltd.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 January 2017
                : 11 May 2017
                : 11 May 2017
                Categories
                Article

                glass design,sintering ability,ion release,biocompatibility,bone substitutes

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