Bioactive glass ceramics: properties and applications

Heat treatment of an MgO-CaO-SiO2-P2O5 glass gave a glass ceramic containing crystalline apatite (Ca10(PO4)6O,F2] and beta-wollastonite (CaO,SiO2) in an MgO-CaO-SiO2 glassy matrix. It showed bioactivity and a fairly high mechanical strength which decreased only slowly, even under load-bearing conditions in the body. It is used clinically as artificial vertebrae, iliac bones, etc. The bioactivity of this glass ceramic was attributed to apatite formation on its surface in the body. Dissolution of calcium and silicate ions from the glass ceramic was considered to play an important role in forming the surface apatite layer. It was shown that some new kinds of bioactive materials can be developed from CaO,SiO2-based glasses. Ceramics, metals and organic polymers coated with bone-like apatite were obtained when such materials were placed in the vicinity of a CaO,SiO2-based glass in a simulated body fluid. A bioactive bone cement which was hardened within 4 min and bonded to living bone, forming an apatite, was obtained by mixing a CaO,SiO2-based glass powder with a neutral ammonium phosphate solution. Its compressive strength reached 80 MPa comparable to that of poly(methyl methacrylate) within 3 d. A bioactive and ferromagnetic glass ceramic containing crystalline magnetite (Fe3O4) in a matrix of CaO,SiO2-based glassy and crystalline phases was obtained by a heat treatment of a Fe2O3-CaO.SiO2-B2O3-P2O5 glass. This glass ceramic was shown to be useful as thermoseeds for hyperthermia treatment of cancer.     

Apatite formation on the surface of Ceravital-type glass-ceramic in the body.

Previous studies on surface structural changes in vitro as well as in vivo of bioactive A-W-type glass-ceramics and Bio-glass-type glasses showed that the essential condition for glasses and glass-ceramics to bond to living bone is formation of a bonelike apatite layer on their surfaces in the body. Gross et al., however, had explained the bone-bonding mechanism of Ceravital-type apatite-containing glass-ceramic without mentioning formation of the surface apatite layer. In the present study, apatite formation on the surface of one of Ceravital-type glass-ceramics was investigated in vitro as well as in vivo. An apatite-containing glass-ceramic of the composition Na2O 5, CaO 33, SiO2 46, Ca(PO3)2 16 wt%, which was named KGS by Gross et al., was soaked in an acellular simulated body fluid which had ion concentrations almost equal to those of the human blood plasma. The same kind of glass-ceramic was implanted into a rabbit tibia. Thin-film x-ray diffraction, Fourier transform infrared reflection spectroscopy, and scanning electron microscopic observation of the surfaces of the specimens soaked in the simulated body fluid showed that Ceravital-type glass-ceramic also forms a layer of carbonate-containing hydroxyapatite of small crystallites and/or a defective structure on its surface in the fluid. Electron probe x-ray microanalysis of the interface between the glass-ceramic and the surrounding bone showed that a thin layer rich in Ca and P is present at the interface. These findings indicated that Ceravital-type glass-ceramics also form the bonelike apatite layer on its surface in the body and bond to living bone through the apatite layer.     

Bone-bonding ability of P2O5-free CaO.SiO2 glasses

An apatite- and wollastonite-containing glass-ceramic (A.W-GC) has been reported to form a tight bond with living bone through an apatite layer formed on its surface. This layer is considered to be formed by dissolution of Ca2+ and HSiO3- ions from the glass-ceramic into the surrounding body fluids. In order to confirm this proposed mechanism for the surface reaction of A.W-GC, three kinds of glass in the systems CaO-SiO2, CaO-SiO2-CaF2, and CaO-SiO2-P2O5 were implanted into the tibiae of rabbits for 3 or 8 weeks. Contact microradiography and SEM-EPMA showed that all three kinds of glass formed a Ca,P-rich layer in combination with a Si-rich layer on their surfaces within 3 weeks and formed a direct bond with bone via these layers. The detaching test, performed 8 weeks after implantation, showed that the loads required to detach the implants from the bone were almost equal for the phosphorus-free and the phosphorus-containing glasses. It was concluded that even P2O5-free CaO.SiO2 glass formed a Ca,P-rich layer on its surface and bonded tightly with living bone. If glasses and glass-ceramics release at least Ca2+ and HSiO3- ions, this would be sufficient for them to form the Ca,P-rich layer on their surfaces in vivo, enabling them to bond directly with bone.     

Novel bioactive and biodegradable glass ceramics with high mechanical strength in the CaO--SiO2--B2O3 system

Novel bioactive and biodegradable glass ceramics with high mechanical strength in the (50-x/2)CaO. SiO(2)--xB(2)O(3) (4.2 < or = x < or = 17.2) system were investigated. The systems consisted of three phases: monoclinic wollastonite, calcium metaborate, and amorphous borosilicate matrix. The glass ceramics containing 4.2 mol% and 8.4 mol% B(2)O(3) showed high bulk density and a dense microstructure. Mechanical strengths of the glass ceramics were higher than those of other bioactive ceramics: high compressive strength (2813 MPa), bending strength of 212 MPa, and fracture toughness of 3.12 MPa. m(1/2). The glass-ceramic formed apatite layer on their surface in the simulated body fluid and showed significant biodegradation. The degree of apatite formation in the glass ceramics depended on the calcium metaborate content and borosilicate glassy matrix. Additional calcium metaborate and borosilicate glassy matrix increased the apatite formation rate on the surface. It might be likely that calcium metaborate causes supersaturation of Ca ions, for its high solubility in SBF and the water-reactive borosilicate glassy matrix formed Sibond;OH groups on the surface to provide nucleation sites for apatite formation. Also, through in vitro test for the biocompatibility of the CaO--SiO(2)--B(2)O(3) glass ceramics, no cytotoxicity of the glass ceramics were found. The results on bioactivity and noncytotoxicity indicated that glass ceramics in the (50-x/2)CaO. SiO(2)--xB(2)O(3) (4.2 < or = x < or = 17.2) system could be useful as a biodegradable bone replacement material.     

Calcium phosphate formation at the surface of bioactive glass in vitro

The calcium phosphate formation at the surface of bioactive glass was studied in vitro. Glass rods and grains were immersed in different aqueous solutions and studied by means of scanning electron microscopy and energy dispersive x-ray analysis. Surface morphological changes and weight loss of corroded grains were monitored. In-depth compositional profiles were determined for rods immersed in the different solutions. The solutions used were tris-buffer (tris-hydroxymethylaminomethane + HCl), tris-buffer prepared using citric acid (tris-hydroxymethylaminomethane + C6H8O7.H2O), and a simulated body fluid, SBF, containing inorganic ions close in concentration to those in human blood plasma. It was found that the calcium phosphate formation at the surface of bioactive glass in vitro proceeds in two stages. When immersing the glass in tris or in SBF a Ca,P-rich surface layer forms. This accumulation takes place within the silica structure. Later, apatite crystals forming spherulites appear on the surface. The Ca/P-ratio of initially formed calcium phosphate was found to be about unity. It is proposed that this is due to bonding of phosphate to a silica gel. The surface is stabilized, i.e., leaching is retarded, by the rapid Ca,P-accumulation within the silica structure before apatite crystals are observed on the surface. It is proposed that the initially formed calcium phosphate is initiated within the silica gel. The crystallizing surface provides nucleation sites for extensive apatite formation on the glass surface. In the presence of citrate no Ca,P-accumulation occur at the glass surface, but soluble Ca-citrate complexes form. By comparing the weight loss during corrosion in tris with that in the calcium and phosphate containing SBF, it is possible to establish whether the glass can induce apatite formation at its surface or not.     

Role of acid attack in the in vitro bioactivity of a glass-ceramic of the 3CaO.P2O5-CaO.SiO2-CaO.MgO.2SiO2 system.

A non-bioactive glass-ceramic (GC13) that contains hydroxyapatite (Ca5(PO4)3OH), diopside (CaMg(SiO3)2) and althausite (Mg2 PO4OH) as crystalline phases has been obtained by thermal treatment of a parent bioactive glass (G13) of nominal composition (wt%) 40.0 CaO-34.5 SiO2-16.5 P2O5-8.5 MgO-0.5CaF2. To induce bioactivity, GC13 was chemically treated with 1 M HCl for different periods of time. After chemical etching the in vitro studies showed formation of an apatite-like surface layer. In this article the influence of etching time both on the surface composition of the glass-ceramic and on the growth rate of the apatite layer is studied. It is concluded that the presence of hydroxyapatite in the glass-ceramic, associated to microstructural fluctuations, can favour apatite deposition in vitro.     

TRIS buffer in simulated body fluid distorts the assessment of glass-ceramic scaffold bioactivity

The paper deals with the characterisation of the bioactive phenomena of glass-ceramic scaffold derived from Bioglass? (containing 77 wt.% of crystalline phases Na(2)O·2CaO·3SiO(2) and CaO·SiO(2) and 23 wt.% of residual glass phase) using simulated body fluid (SBF) buffered with tris-(hydroxymethyl) aminomethane (TRIS). A significant effect of the TRIS buffer on glass-ceramic scaffold dissolution in SBF was detected. To better understand the influence of the buffer, the glass-ceramic scaffold was exposed to a series of in vitro tests using different media as follows: (i) a fresh liquid flow of SBF containing tris (hydroxymethyl) aminomethane; (ii) SBF solution without TRIS buffer; (iii) TRIS buffer alone; and (iv) demineralised water. The in vitro tests were provided under static and dynamic arrangements. SBF buffered with TRIS dissolved both the crystalline and residual glass phases of the scaffold and a crystalline form of hydroxyapatite (HAp) developed on the scaffold surface. In contrast, when TRIS buffer was not present in the solutions only the residual glassy phase dissolved and an amorphous calcium phosphate (Ca-P) phase formed on the scaffold surface. It was confirmed that the TRIS buffer primarily dissolved the crystalline phase of the glass-ceramic, doubled the dissolving rate of the scaffold and moreover supported the formation of crystalline HAp. This significant effect of the buffer TRIS on bioactive glass-ceramic scaffold degradation in SBF has not been demonstrated previously and should be considered when analysing the results of SBF immersion bioactivity tests of such systems.     

Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W

High-strength bioactive glass-ceramic A-W was soaked in various acellular aqueous solutions different in ion concentrations and pH. After soaking for 7 and 30 days, surface structural changes of the glass-ceramic were investigated by means of Fourier transform infrared reflection spectroscopy, thin-film x-ray diffraction, and scanning electronmicroscopic observations, in comparison with in vivo surface structural changes. So-called Tris buffer solution, pure water buffered with trishydroxymethyl-aminomethane, which had been used by various workers as a "simulated body fluid," did not reproduce the in vivo surface structural changes, i.e., apatite formation on the surface. A solution, ion concentrations and pH of which are almost equal to those of the human blood plasma--i.e., Na+ 142.0, K+ 5.0, Mg2+ 1.5, Ca2+ 2.5, Cl- 148.8, HCO3- 4.2 and PO4(2-) 1.0 mM and buffered at pH 7.25 with the trishydroxymethyl-aminomethane--most precisely reproduced in vivo surface structure change. This shows that careful selection of simulated body fluid is required for in vitro experiments. The results also support the concept that the apatite phase on the surface of glass-ceramic A-W is formed by a chemical reaction of the glass-ceramic with the Ca2+, HPO4(2-), and OH- ions in the body fluid.     

Bioactivity of tape cast and sintered bioactive glass-ceramic in simulated body fluid

A common ceramic processing technique, tape casting, was used to produce thin, flexible sheets of bioactive glass (Bioglass 45S5) particulate in an organic matrix. Tape casting offers the possibility of producing three-dimensional shapes, as the final material is built up layer by layer. Bioactive glass tapes were sintered together to form small discs for in vitro bioactivity testing in simulated body fluid (SBF). Four different sintering schedules were investigated: 800, 900, and 1000 degrees C for 3 h; and 1000 degrees C for 6 h. Each schedule produced a crystalline material of major phase Na2Ca2Si3O9. Tape cast and sintered bioactive glass-ceramic processed at 1000 degrees C formed crystalline hydroxyapatite layers after 20-24 h in SBF as indicated by Fourier transform infrared spectroscopy, Scanning electron microscopy, and EDS data. FTIR revealed that the greatest amount of hydroxyapatite formation after 2 h was observed for samples sintered at 900 degrees C. The differences in bioactive response were likely caused by the variation in the extent of sintering and, consequently, the amount of surface area available for reaction with SBF.     

In vitro bioactivity of glass and glass-ceramics of the 3CaO x P2O5-CaO x SiO2-CaO x MgO x 2SiO2 system

A glass of nominal composition (wt%) 40.0 CaO-34.5 SiO2-16.5 P2O5-8.5 MgO-0.5 CaF2 has been obtained (G13). The glass showed in vitro bioactivity evidenced by the formation on its surface of a calcium phosphate-rich layer when soaked in a solution with ionic composition analogous to human plasma. By thermal treatments of G13, a glass-ceramic (GC13) containing apatite, diopside, althausite and akermanite as crystalline phases was developed. GC13 as-made did not show in vitro bioactivity. However, after chemical treatment of GC13 with 1 M HCl (GC13-HCl), the in vitro studies showed the formation of an apatite-like layer covering certain areas of the material surface. The influence of both chemical and morphological factors on the in vitro bioactivity has been studied.     

Bioactive ceramics prepared by sintering and crystallization of calcium phosphate invert glasses.

Novel glass-ceramics were synthesized via sintering and crystallization by heating powder compacts of SiO2-free calcium phosphate invert glasses of 60CaO x 30P2O5 x 7Na2O x 3TiO2 or 60CaO x 30P2O5 x 7Na2O x 3MgO at 800-850 degrees C in air. The glass-ceramics were relatively dense materials consisting of crystalline phases such as beta-Ca3(PO4)2 and beta-Ca2P2O7 with glassy phases. The compacts were densified by the viscous flow of the glassy phases while heating. By soaking in simulated body fluid at 37 degrees C, a calcium phosphate phase was formed newly on the surface of the glass-ceramic derived from 60CaO x 30P2O5 x 7Na2O x 3TiO2 glass, while the phase was not formed on that derived from 60CaO x 30P2O5 x 7Na2O x 3MgO glass: the former was implied to show bioactivity. Composition of the glassy phase as the matrix varies with the additives such as TiO2 and MgO, and the chemical properties of the phase influence the bioactivity of the glass-ceramics. The glass-ceramic derived from 60CaO x 30P2O5 x 7Na2O x 3TiO2 glass has relatively high fracture toughness of K(IC) approximately 2 MPa m(0.5) and bending strength of 100-120 MPa.     

Porous bioactive glass and glass-ceramics made by reaction sintering under pressure

A glass and a rhenanite-wollastonite glass-ceramic were synthesized with the qualitative composition Na2O-CaO-SiO2-P2O5. Both materials were prepared by reaction sintering under isostatic pressure (RSIP) using powder mixtures. Solid state reactions were complete within a few hours at 950 degrees C under modest pressure. Formation of the glass and crystalline phases was driven by an intermediate, reactive, low viscosity Na2O-SiO2 phase. A reaction mechanism is suggested. Porous materials were obtained with two ranges of pore sizes: 100-200 microm and < or =5 microm in diameter. The glass and the glass-ceramic were corroded in simulated body fluid at 37 degrees C. The evolution of surface features was studied. Gel layers formed on both materials. Corrosion was fastest inside the pores. Microcrystals of apatite were identified by crystal structure analysis and by chemical analysis. During corrosion of the glass-ceramic, rhenanite most likely was converted into apatite. Comparison of these results with published information suggests that the glass and glass-ceramic are bioactive. We suggest that RSIP can be used (a) to control the surface porosity and pore size of bioactive implants, thereby increasing the stability of tissue/implant interfaces; (b) to make glasses and glass-ceramics with new properties; and (c) to make near net-shape materials.     

Bioactivity of plasma sprayed dicalcium silicate coatings.

Dicalcium silicate coatings on titanium alloys substrates were prepared by plasma spraying and immersed in simulated body fluids for a period of time to investigate the nucleation and growth of apatite on the surface of the coatings. Surface structural changes of the specimens were analyzed by XRD and IR technologies. SEM and EDS were used to observe surface morphologies and determine the composition of dicalcium silicate coatings before and after immersion in simulated body fluid. The plasma sprayed dicalcium silicate coating was bonding tightly to the substrate. The coating was mainly composed of beta-Ca2SiO4 and glassy phase. A dense carbonate-containing hydroxyapatite (CHA) layer was formed on the surface of the plasma sprayed dicalcium silicate coating soaked in SBF solution for 2 days. In addition, a silica-rich layer was also observed between CHA layer and coatings. With an increase in the immersion time, the CHA layer gradually became thicker. The results obtained indicated that the plasma sprayed dicalcium silicate coating possesses excellent bioactivity.     

CaO-P2O5 glass hydroxyapatite double-layer plasma-sprayed coating: in vitro bioactivity evaluation.

Double-layer composite coatings composed of a P2O5-based glass/Ca10(PO4)6(OH)2 (HA) mixture top layer and a simple HA underlayer, on Ti-6Al-4V substrates, were prepared using a plasma-spraying technique. The in vitro bioactivity of these coatings was assessed by immersion testing in simulated body fluid. Both scanning electron microscopy (SEM) analysis and the ionic solution changes followed by atomic absorption spectroscopy and the molybdenum blue method demonstrated that these composite coatings induce a faster surface Ca-P layer formation than the simple HA coatings used as a control. X-ray photoelectron spectroscopy (XPS) analysis demonstrated that the Ca-P layer formed was apatite. The combination of SEM and XPS analyses showed that the apatite layer was a calcium-deficient hydroxyapatite with a Ca/P ranging from 1.3 to 1.4 with CO3(2-) groups contained in the structure.     

新型多孔磷灰石/硅灰石生物活性玻璃陶瓷材料的研究

通过溶胶 -凝胶工艺制备了一种新型玻璃陶瓷材料 ,X衍射图谱及傅立叶转换红外图谱表明该材料主晶相为含羟基基团的氟氧磷灰石 [Ca10 (PO4) 6(OH ,F) ]和 β 硅灰石 [β CaSiO3 ];扫描电镜分析显示材料显微结构含有大量微孔 ,孔径为 2～ 3μm。经造孔后 ,材料大孔孔径为 30 0～ 4 0 0 μm ,且孔道相互贯通 ;采用体外模拟体液浸泡实验表征了材料的生物活性 ,扫描电镜观测发现 ,材料表面 7天内已生成大量羟基磷灰石晶粒。结果表明 :采用新型溶胶 -凝胶工艺制备的磷灰石 / β 硅灰石玻璃陶瓷材料具有良好的生物活性 ,其多孔材料具有适宜的孔隙结构 ,微观孔与宏观孔相结合 ,是一类十分具有发展潜力的骨组织修复材料及骨组织工程支架材料。     

Effect of ZnO addition on bioactive CaO-SiO2-P2O5-CaF2 glass-ceramics containing apatite and wollastonite

Some ceramics show bone-bonding ability, i.e. bioactivity. Apatite formation on ceramics is an essential condition to bring about direct bonding to living bone when implanted into bony defects. A controlled surface reaction of the ceramic is an important factor governing the bioactivity and biodegradation of the implanted ceramic. Among bioactive ceramics, glass-ceramic A-W containing apatite and wollastonite shows high bioactivity, as well as high mechanical strength. In this study, glass-ceramics containing zinc oxide were prepared by modification of the composition of the glass-ceramic A-W. Zinc oxide was selected to control the reactivity of the glass-ceramics since zinc is a trace element that shows stimulatory effects on bone formation. Glass-ceramics were prepared by heat treatment of glasses with the general composition: xZnOx(57.0-x)CaOx35.4SiO(2)x7.2P(2)O(5)x0.4CaF(2) (where x=0-14.2mol.%). Addition of ZnO increased the chemical durability of the glass-ceramics, resulting in a decrease in the rate of apatite formation in a simulated body fluid. On the other hand, the release of zinc from the glass-ceramics increased with increasing ZnO content. Addition of ZnO may provide bioactive CaO-SiO(2)-P(2)O(5)-CaF(2) glass-ceramics with the capacity for appropriate biodegradation, as well as enhancement of bone formation.     

Interfaces in graded coatings on titanium-based implants

Graded bilayered glass-ceramic composite coatings on Ti6Al4V substrates were fabricated using an enameling technique. The layers consisted of a mixture of glasses in the CaO-MgO-Na(2)O-K(2)O-P(2)O(5) system with different amounts of calcium phosphates (CPs). Optimum firing conditions have been determined for the fabrication of coatings having good adhesion to the metal, while avoiding deleterious reactions between the glass and the ceramic particles. The final coatings do not crack or delaminate. The use of high-silica layers (>60 wt % SiO(2)) in contact with the alloy promotes long-term stability of the coating; glass-metal adhesion is achieved through the formation of a nanostructured Ti(5)Si(3) layer. A surface layer containing a mixture of a low-silica glass ( approximately 53 wt % SiO(2)) and synthetic hydroxyapatite particles promotes the precipitation of new apatite during tests in vitro. The in vitro behavior of the coatings in simulated body fluid depends both on the composition of the glass matrix and the CP particles, and is strongly affected by the coating design and the firing conditions.     

XRD, SEM-EDS, and FTIR studies of in vitro growth of an apatite-like layer on sol-gel glasses.

A glass with a composition (in mole %) of: SiO2 (70), CaO (26), and P2O5 (4) was obtained using a sol-gel method. The in vitro bioactivity of the glass was assessed by determining the changes in surface morphology and composition after soaking in simulated body fluid (SBF) for periods of up to 14 days at 37 degrees C. X-ray diffraction, scanning electron microscopy, X-ray energy dispersive spectroscopy, and FTIR analyses of the glass surface after different soaking periods in SBF demonstrated the growth of an apatite-like layer on the glass surface. In the first stage, an amorphous calcium phosphate layer was formed; after 7 days this surface consisted of spheres, with diameters ranging between 2 and 15 microm, composed of needle-like apatite crystallites (250 x 100 nm) with a crystallinity similar to that of a biological apatite.     

A comparative study of ultrastructures of the interfaces between four kinds of surface-active ceramic and bone.

The interfaces between four kinds of surface-active ceramic and bone were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) using undecalcified specimens. The materials were Bioglass-type glass (Bioglass), Ceravital-type glass-ceramic (KGS), apatite- and wollastonite-containing glass-ceramic (A-W.GC) and hydroxyapatite (HA). Particles of these materials, ranging between about 100 and 300 microns in diameter, were implanted into rat tibiae, and specimens were prepared for observation at 8 weeks after implantation. All materials were observed to bond to bone through a collagen-free layer consisting of fine apatite crystals distinct from those in bone. The crystals of this apatite layer and those of bone were intermingled at their interface, suggesting chemical bonding. In Bioglass, which had only a glassy phase, several tens of microns of the material surface had changed to such an apatite layer. In KGS and A-W.GC, which had macrocrystals in the glassy phase, an intervening apatite layer about 0.5 micron thick was observed between the materials and bone. Furthermore, fine apatite crystals were also observed among the macrocrystals near the surface of the materials. In HA, which had no glassy phase, an intervening apatite layer was much less distinct and sometimes absent. These differences were considered to be attributable to the differences in chemical composition, crystallization, and solubility of the materials.     

Effect of silane treatment and different resin compositions on biological properties of bioactive bone cement containing apatite-wollastonite glass ceramic powder.

In methylmethacrylate (MMA)-based cements containing bioactive particles, polymethylmetacrylate (PMMA) is known to suppress the bioactivity of Bioglass(R) and apatite-wollastonite glass ceramic (AW-GC). Little is known about the effect of different silane treatment methods on the bioactivity of AW-GC. MMA-based cement plates containing dry silanated AW-GC particles and PMMA particles of different molecular weights (12,000-900,000) were immersed in simulated body fluid (SBF). Cements containing PMMA particles of high molecular weight formed an apatite layer on the surface after 24 h. Using PMMA particles with a molecular weight of 60,000 and AW-GC particles silanated with different methods (dry method vs. slurry method), cement plates were made and immersed in SBF. Only cement plates containing dry silanated AW-GC particles showed apatite formation in SBF after 3 days. In vivo implantation in rat tibias of MMA-based cement containing dry silanated AW-GC particles and PMMA particles (molecular weight 900,000) demonstrated an affinity index of 32.1 +/- 15.8% after 8 weeks of implantation compared to 89.4 +/- 10.7% achieved by bisphenol-A-glycidyl methacrylate based cement containing the same bioactive powder. By using a dry method of silane treatment and high molecular weight PMMA particles, the bioactivity of cement based on MMA monomer was achieved; but further effort is needed to improve the mechanical properties of the composite.