Characterization,in vitro bioactivity and biological studies of sol-gel synthesized SrO substituted 58S bioactive glass

Bioactive glasses (BGs) are considered as a high potential candidate in bone repair and replacement. In the present study, sol–gel derived BGs based on 60% SiO₂-(36%-x) CaO-4%P₂O₅-x SrO (where x = 0, 5 and 10 mol%) quaternary system were synthesized and characterized. The effect of Sr substitutions on bioactivity, proliferation, alkaline phosphatase activity of osteoblast cell line MC3T3-E1 and antibacterial activity were investigated. Dried gels were stabilized at 700 °C to eliminate the nitrates and prevent the crystallization of bioactive glasses. X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy results confirmed the formation of hydroxycarbonate apatite on the BG surfaces. The 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and alkaline phosphate activity results showed that 5% SrO increased both differentiation and proliferation of MC3T3-E1 cells, while 10% SrO resulted in a decrease in bioactivity. Live/Dead and DAPI/Actin staining exhibited viable cell and the morphology of actin fibers and nuclei of MC3T3 cells treated with BG-0 and BG-5. The result of antibacterial test showed that strontium substituted 58S BG exhibited antibacterial effect against methicillin-resistant Staphylococcus aureus bacteria. Taken together, results suggest that 58S BG with 5 mol% SrO is a good candidate for bone tissue engineering with maximum cell proliferation and ALP activity, good bioactivity and high antibacterial efficiency.     

Characterization,in vitro bioactivity and biological studies of sol-gel-derived TiO2 substituted 58S bioactive glass

Bioactive glasses (BGs) have been used for bone formation and bone repair processes in recent years. This study investigated the titanium substitution effect on 58S BGs (Ti-BGs) 60SiO₂-(36 − X)CaO-4P₂O₅-XTiO₂ (X = 0, 3, and 5 mol.%) prepared by the sol-gel technique, and the main goal was to find the optimum amount of titanium in Ti-BGs. Synthesized BGs, which were investigated after immersion in simulated body fluid (SBF), were tested by X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy. Moreover alkaline phosphate (ALP) activity, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and antibacterial studies were employed to investigate the biological properties of Ti-BGs. According to the FTIR and XRD test results, hydroxyapatite (HA) formation on Ti-BGs surfaces was confirmed. Meanwhile, the presence of 5 mol.% compared to 3 mol.% increased the HA grain distribution and their size on the Ti-BGs surface. Additionally, MTT and ALP results confirmed that the optimal amount of titanium substitution in BG was 5 mol.%. Since 5 mol.% Ti incorporated BG (BG-5) had the highest biocompatibility level, antibacterial properties, maximum cell proliferation, and ALP activity among the synthesized Ti-BGs, it is presented as the best candidate for further in vivo investigations.     

Fabrication and characterization of bioactive glass/hydroxyapatite nanocomposite foam by gelcasting method

Bioceramic foams have been applied for drug releasing agents, cell loading, and widely for hard tissue scaffold. The aim of this study was fabrication and characterization of nanostructure bioceramic composite foam (BCF) consisting of hydroxyapatite (HA) and bioactive glass (BG) via gelcasting method for applications in tissue engineering. X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis techniques were utilized in order to evaluate respectively, phase composition, dimension, morphology, and interconnectivity of pores, and particle size of synthesized HA, BG, and BCF. The results showed that fabrication of the BCF with a particle size in the range 20-42 nm and pore size in the range 100-250 μm was successfully performed. The maximum values of compressive strength and elastic modulus of the BCF were found to be about 1.95 MPa and 204 MPa, respectively, related to a sample sintered at 900 °C for 4 h. The mean values of the true (total) and apparent (interconnected) porosity were calculated in the range 86-91% and 60-71%, respectively. It seems that the measured properties make the BCF a good candidate for tissue engineering applications, preferentially in drug delivery, cell loading, and other nonloading applications.     

Synthesis and characterization of spray pyrolyzed mesoporous bioactive glass

Mesoporous bioactive glasses (MBGs) have recently been applied as important bone implant materials due to their high reactive surface areas and superior bioactivities. Various processes have been developed to fabricate MBGs. Among them, the sol–gel process is one of most popular. However, sol–gel has the drawbacks of discontinuous processing and long processing time, making it unsuitable for mass production. This study demonstrates a successful synthesis of MBGs using a spray pyrolysis (SP) method to overcome these problems. The bioactivities of the SP synthesized MBGs are correlated with the main SP processing parameter of calcination temperatures and their structures. Comparisons of the surface areas and bioactivities for the MBG particles prepared from the sol–gel and the SP process are included. Finally, the MBG formation mechanism using SP is proposed.     

WS2/bioactive glass composites: Fabrication,structural, mechanical and radiation attenuation properties

Ionizing radiation interaction might occur during diagnostic imaging and radiotherapy procedures. It has been reported that gamma-ray radiation can damage the living cells through the energy transfer. Therefore, investigation the ionization radiation attenuation properties of biomaterials have a crucial importance. In the current study, tungsten disulphide (WS₂) nanopowder-containing borate-based bioactive glass composites were prepared. Their physical, structural, mechanical and ionization radiation attenuation properties were investigated in detail. Monte Carlo simulations and radiation attenuation properties were studied through MCNPX and Phy-X/PSD. Results showed that sintering performed at 575 °C for 1 h in air atmosphere caused formation of some tungsten trioxide in the structure. Addition of WS₂ nanopowders increased the bulk density and improved the mechanical properties of the prepared bioactive glass composites. Simulation studies revealed the influence of WS₂ content on reduction the build-up factors and enhancement of the photon attenuation ability for all the considered photon energies.     

Synthesis and characterization of bioactive forsterite nanopowder

Forsterite ceramic is a new bioceramic with good biocompatibility. However, the degradation rate of forsterite ceramic is extremely low, and the apatite-formation ability is also poor. On the other hand, nanostructured bioceramics are expected to have better bioactivity than coarser crystals. The aim of this work was preparation, characterization and bioactivity evaluation of forsterite nanopowder. Forsterite nanopowder was synthesized by the sol–gel process. Bioactivity evaluation was preformed by immersing the forsterite powder in the simulated body fluid (SBF) and apatite formation on the surface of the immersed forsterite nanopowders was investigated. Results showed the particle size of pure forsterite was 25–45 nm. During immersion in SBF, the dissolution rate of the forsterite nanopowder was higher than conventional forsterite powders and apatite was formed after soaking for 14 days. Our study indicated that forsterite nanopowder unlike micron-sized forsterite possessed apatite-formation ability and might be used for preparation of new biomaterials.     

Synthesis, characterization and in vitro bioactivity of magnesium-doped sol-gel glass and glass-ceramics

Bioactive glass and glass-ceramics in the system CaO-MgO-SiO₂-P₂O₅ have been prepared by the sol-gel and high temperature sintering techniques. The obtained samples were characterized by thermogravimetric and differential thermal analysis (TG/DTA), N₂-adsorption measurement, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). In vitro bioactivity tests were also conducted in simulated body fluid (SBF). The studies of crystallization kinetics under non-isothermal conditions showed the activation energy for crystallization to be 381 kJ/mol and the crystallization mechanism gradually changed from three-dimension growth to two-dimension crystallization with the increase of heating rate. Sintering temperature had great influence on the samples texture and structure. In addition, the apatite-formation on glass and glass-ceramics was confirmed by in vitro tests, and crystallization decreased the samples bioactivity.     

Synthesis, characterization and microbiological response of silver doped bioactive glass nanoparticles

Glass nanoparticles containing 1, 3, 5, and 10 wt% of Ag₂O (coded; GAg1%, GAg3%, GAg5%, and GAg10%, respectively) were synthesized through a quick alkali mediated sol-gel method and were characterized by TEM, XRF, FT-IR, XRD, TGA, and DSC. Thermal analysis showed that all organic and inorganic by-products were completely decomposed before 700 °C and, hence, all glass samples were stabilized at this temperature. XRD confirmed the amorphous nature of all glasses after stabilization. TEM micrographs showed that the average particle sizes of all samples were less than 100 nm in diameter and the XRF showed that the compositions of the obtained glasses were almost consistent with the designed ones. The samples GAg1%, GAg3%, GAg5%, and GAg10%, showed average pore diameters of 19.85, 18.22, 13.32, and 19.62 nm and specific surface areas of 73.18, 100.38, 192.6, and 55.7 m²/g, respectively. In addition, their porosity% was 76.53, 83.20, 77.97, and 79.61%, respectively. The FT-IR spectra of all glasses showed bands located in the range of 1000-1200, 725-800, and 450-480 cm⁻¹ that correspond to the Si-O-Si asymmetric stretching vibration, the Si-O-Si symmetric stretching vibration, and the Si-O-Si bending mode, respectively. Finally, all samples had an anti-bacterial effect against different types of bacteria and the extraction of silver ions from them followed a diffusion-controlled mechanism, which could demonstrate their ability to treat bone infection.     

In vitro assessment of degradation and bioactivity of robocast bioactive glass scaffolds in simulated body fluid

In this study porous three-dimensional scaffolds of borate (13-93B3) bioactive glass were prepared by robocasting and in vitro degradation and bioactivity was evaluated. Grid like scaffolds with interconnected pores was assembled using robotic deposition technique which is a direct ink writing method. After binder burnout, the constructs were sintered for 1 h at 560 °C to produce scaffolds (porosity≈60%) consisting of dense glass struts (300±20 μm in diameter) and interconnected pores of width 580±20 μm. Hydroxyapatite formation on borate bioactive glass scaffolds was investigated in simulated body fluid (SBF) using three different scaffold/SBF (S/S) ratios (1, 2 and 10 mg/ml) at 37 °C. When immersed in SBF, degradation rate of the scaffolds and conversion to a calcium phosphate material showed a strong dependence to the S/S ratio. At high solid concentration (10 mg/ml) surface of the glass scaffolds converted to the calcium rich amorphous calcium phosphate after 30 days. At lower solid concentrations (2 and 1 mg/ml) an amorphous calcium phosphate layer formation was observed followed by the conversion to hydroxyapatite.     

Modification of mesoporous structure of silver-doped bioactive glass with antibacterial properties for bone tissue applications

Silver-containing mesoporous bioglasses powders with SiO₂–CaO–P₂O₅–Ag₂O composition have been successfully synthesized by sol-gel and evaporation-induced self-assembly (EISA) methods in presence of various amounts of surfactant (Pluronic-F127). The morphology and crystal structure of the powders were characterized by scanning electron microscopy (SEM) and X-ray diffraction spectroscopy (XRD). Also, the textural properties of samples have been evaluated by adsorption-desorption, Langmuir and BET methods. Accordingly, powders had a smooth surface morphology with cubic mesoporous structure and a desired surface area and pore volume. The in vitro bioactivity was assessed by SEM, XRD and Fourier transform infrared spectroscopy (FTIR) analyses. All samples enhance the formation of HA after soaking the material in simulated body fluid (SBF) solution. The antibacterial property of samples was evaluated to investigate the effect of silver content in chemical composition. The results showed an adequate antibacterial activity of the samples against Escherichia coli, Salmonella and Listeria monocytogenes.     

In vitro behavior of bioactive phosphate glass–ceramics from the system P2O5–Na2O–CaO containing titania

Soda lime phosphate bioglass–ceramics with incorporation of small additions of TiO₂ were prepared in the metaphosphate and pyrophosphate region, using an appropriate two-step heat treatment of controlled crystallization defined by differential thermal analysis results. Identification and quantification of crystalline phases precipitated from the soda lime phosphate glasses were performed using X-ray diffraction analysis. Calcium pyrophosphate (β-Ca₂P₂O₇), sodium metaphosphate (NaPO₃), calcium metaphosphate (β-Ca(PO₃)₂), sodium pyrophosphate (Na₄P₂O₇), sodium calcium phosphate (Na₄Ca(PO₃)₆) and sodium titanium phosphate (Na₅Ti(PO₄)₃) phases were detected in the prepared glass–ceramics. The degradation of the prepared glass–ceramics was carried out for different periods of time in simulated body fluid at 37 °C using granules in the range 0.300–0.600 mm. The released ions were estimated by atomic absorption spectroscopy and the surface textures were measured by scanning electron microscopy. Investigation of in vitro bioactivity of the prepared glass–ceramics was done by the measurement of the infrared reflection spectra for the samples after immersion in the simulated body fluid for different periods at 37 °C. The result showed that no apatite layer was formed on the surface of the samples and the dominant phase remained on the surface was β-Ca₂P₂O₇, which is known for its bioactivity.     

Development of macroporous nanocomposite scaffolds of gelatin/bioactive glass prepared through layer solvent casting combined with lamination technique for bone tissue engineering

In this study, macroporous bioactive nanocomposite scaffolds were developed using cross-linked gelatin and bioactive glass (BaG) nanoparticles. First, BaG nanoparticles were synthesized via sol–gel method and characterized. Then, macroporous nanocomposites were prepared through layer solvent casting combined with freeze-drying and lamination techniques. This research has developed a new composition to produce a new bioactive nanocomposite which is porous with three-dimensional (3D) inter-connected microstructure, pore sizes are 200–500 μm, porosity are 72–86% and BaG nanoparticles are dispersed evenly among cross-linked gelatin matrices. It is mentionable that in this study, we have reported the formation of chemical bonds between BaG nanoparticles and gelatin for the first time. Finally, the in vitro cytocompatibility of the nanocomposite scaffolds was tested using SaOS-2 cell line.     

Synthesis and characterization of CaFe2O4 nanoparticles via co-precipitation and auto-combustion methods

In this paper, the techniques for the synthesis of CaFe₂O₄ nanoparticles using the auto-combustion and co-precipitation methods are discussed. The effects of both methods on the microstructure and magnetic properties of the CaFe₂O₄ nanoparticles were compared. The CaFe₂O₄ powder was obtained after drying the synthesized sample via co-precipitation overnight in an oven at 80 °C. For auto-combustion method, the sol that was initially formed was gradually converted into a gel, which was then combusted at 250 °C. Finally, the CaFe₂O₄ nanoparticles were calcined at 550 °C. The different synthesis methods produced nanoparticles with different physical and magnetic properties in order to find an optimum size to be utilized for drug delivery applications. The results of the X-ray diffraction showed that both processes produced nanocrystals with an orthorhombic crystalline structure. It was noted from the measurements made with a transmission electron microscope (TEM) that the synthesis using the co-precipitation method produced nanoparticles with a size of about 10–20 nm, which was comparable with the size that was obtained when the auto-combustion method was used. The magnetic properties were investigated using a vibrating sample magnetometer (VSM), where the magnetic saturation (M_s) of CaFe₂O₄ for the sample synthesized using the co-precipitation method was 47.279 emu/g, which was higher than the magnetic saturation (M_s) of 31.10 emu/g obtained when the auto-combustion method was used. The hysteresis loops (Hc) for the samples were 17.380 G and 6.1672 G, respectively. Additionally, the elaborate properties mentioned above, such as the size and superparamagnetic properties of the synthesized CaFe₂O₄ nanoparticle size, were the characteristics required for drug delivery because the targeted therapy required nanoparticles with good magnetic properties, a suitable size, and which were non-toxic in order to have a potential application in targeted drug delivery systems.     

Structural, optical and bioactive properties of calcium borosilicate glasses

Glass of composition 40SiO₂–20B₂O₃–30CaO–10M₂O₃ (M = Al, Cr, Y and La) were prepared by the splat quenching technique to investigate the effect of M₂O₃ on their bioactivity, structural and optical properties. Y₂O₃ and Cr₂O₃ containing glasses formed a crystalline hydroxyapatite (HA) layer after dipping in simulating body fluid (SBF) for 25 days. On the other hand, HA layer could not form in Al₂O₃ and La₂O₃ glasses. However, during soaking in SBF solution, these glasses exhibit higher dissolution rate, lower density and increased optical band gap as compared to unsoaked glasses. Their oxygen molar volume was also higher than for Y₂O₃ and Cr₂O₃ glasses. The change in composition affects the cross-link formation in the glass matrix and finally its durability and bioactivity in SBF. The results show that M₂O₃ plays an important role in controlling chemical durability and bioactivity of the glasses.     

Bioactivity and osteoinductivity of glasses and glassceramics and their material determinants

Bioactive glasses and glassceramics have been used in both bone repair and tissue engineering applications. An important feature of bioactive glasses and glassceramics, which enables them to be used for desired application, is their biological activity. This activity is manifested by the ability of these materials to form a stable bond with bone tissue (bioactivity) and, in some cases, their ability to promote/initiate osteogenesis (osteoinductivity). A stable material-bone bonding (i.e. bioactivity) results from specific material surface reactions leading to hydroxyapatite (HAp) formation on the material surface. Bioactivity of materials is often evaluated in vitro and the ability of materials to form HAp-like surface layer is usually studied after immersion/incubation of materials in simulated body fluid (SBF). Biological activity of materials can be also defined as their ability to induce specific cell responses leading to faster regeneration of bone tissue. It may be manifested by materials supporting bone cell attachment, proliferation and differentiation (biocompability/osteconductivity), and/or by materials inducing/promoting the expression of multiple bone-related genes that drive osteogenesis (osteoinductivity). Osteoinductivity is often verified in vivo by the materials capability to form bone at etopic (i.e. extraskeletal) sites. However, a lot of in vitro call-based experiments are now offered to determine osteoinductive properties of biomaterials. This review focuses on the silica-based glasses and glass-ceramics, in particular, the sol-gel derived ones, and summarizes their bioactivity and osteoinductivity as major determinants of their biological activity. We highlight the chemistry of bioglasses and glassceramics that affects not only the formation of a stable implant/bone bonding by HAp layer, but also drives the cell response in vitro and in vivo.     

Bioactive glass-ceramics prepared by powder sintering and crystallization of polyphosphate glass containing strontium

Melt-quenching method was employed for obtaining a glass-ceramic with the following composition 42P₂O₅·40CaO·5SrO·10Na₂O·3TiO₂ (mol%) glass. The crystallization and sintering behavior of glass have been studied by using DTA, HSM, XRD, FTIR and SEM methods. It was determined that the surface and volume crystallization mechanisms act simultaneously in bulk glass samples. The comparison of DTA and HSM data revealed that the sintering and crystallization processes are independent. The sintered calcium phosphate glass-ceramic which contained bioactive β-Ca₃(PO₄)₂ and β-Ca₂P₂O₇ phases was successfully prepared. It was determined that during crystallization the primary phase in the precipitate was β-Ca(PO₃)_2. Other phases appearing in the resulting glass-ceramic were: α-Ca₂P₂O₇, γ-Ca₂P₂O₇, Ca₄P₆O₁₉ and CaHPO₄(H₂O)₂. Crystalline phases containing Sr and Ti were not detected. SEM analysis of the glass-ceramic microstructure revealed surface crystallization of glass particles and plate-like morphology of crystal growth. The result of the in vitro bioactivity showed that no apatite layer was formed on the surface of the as-prepared glass-ceramic samples after immersion in the simulated body fluid (SBF).     

Fabrication and in vitro characterization of antibacterial magneto-luminescent core-shell bioactive glass nanoparticles

When nanomaterials with antibacterial properties were sent to the infected area, it was predicted that infection and related complications could be prevented. The nanoparticles can be designed to possess magnetic and luminescence (magneto-luminescent) properties to be effectively targeted and localized at the infection foci without dispersing into the body. Simultaneously, the magneto-luminescent characteristic of particles allows visualization and confirmation of localized particles at the desired area. In this regard, there are no studies on the use of antibacterial magneto-luminescent bioactive glass for orthopedic applications and the treatment of orthopedic device-related infections. In this study, antibacterial magneto-luminescent 58S bioactive glasses were synthesized by the modified Stöber using coupled with a layer-by-layer assembly approach to possess core/shell particle morphology. SPION/Bioactive glass nanoparticles had an average size of 50 nm and displayed superparamagnetic behavior. While the saturation magnetization value (σ_s) of the undoped 58S sample was 25.32 emu/g, that of the co-doped sample (2% Eu, 2% Zn) was 21.74 emu/g; this showed that the doping slightly reduced the magnetization value. Europium (Eu) doping of SPION/Bioactive glass nanoparticles induced characteristic red emission originating from Eu emissions belonging to ⁵D₀–⁷F_J (J = 1–4) transitions and the strongest peak was at 612 nm (electric-dipole transition, ⁵D₀–⁷F₂). Color chromaticity coordinates confirmed emission in the red region. XPS spectrum revealed the existence of Eu and Zn dopant elements in 58S bioactive glass. After soaking characteristic peaks at 31.74° and 45.43° belonging to the hexagonal hydroxyapatite phase were detected in the XRD data, confirming the SEM images. 2% Eu doped SPION/Bioactive glass nanoparticles had the highest osteoblast viability up to 7 days in vitro, while doping the samples with 2% zinc did not yield bone cell viability as high as the Eu doped ones. Importantly, Eu doped SPION/Bioactive glass nanoparticles inhibited gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) growth up to 48 h in vitro. The results showed that Eu doping of SPION/Bioactive glass nanoparticles increased osteoblast viability and inhibited bacterial growth, while possessing superparamagnetic properties and exhibiting red luminescence.     

Preparation and characterization of some multicomponent silicate glasses and their glass–ceramics derivatives for dental applications

The chemical corrosion and UV–vis absorption and infrared absorption spectra of binary and multicomponent lithium silicate glasses and corresponding glass–ceramics were investigated. The chemical durability of the glasses and derived glass–ceramics was found to be excellent to all leaching media. The IR absorption spectra of the glass and glass–ceramic samples reveal absorption bands of characteristic groups mainly due to major silicate network besides the possible sharing of network units due to some involving oxide constituents. X-ray analysis of glass–ceramics indicates the separation of lithium disilicate phase as the main constituent beside other phases according to the specimen chemical constituents. The obvious promising investigated chemical and physical properties are correlated with the presence of multioxides such as Al₂O₃, TiO₂, MgO and ZrO₂. Transmission and reflectivity properties reveal acceptable data. The prepared glass–ceramics are recommended for dental applications.     

Influence of silver on the structure,dielectric and antibacterial effect of silver doped bioglass-ceramic nanoparticles

We present the structural, dielectric, biocompatibility and antibacterial properties of nano-sized calcium phosphosilicate bioglass ceramics doped with 0, 2, 4 and 6 mol% Ag₂O. Sol-gel processes were chosen to synthesize the silver embedded nanosized glass ceramic particles. All samples were characterized by powder X-ray diffraction (XRD), thermogravimetric analysis, Fourier transform infrared (FTIR) spectroscopy, UV–visible and high resolution transmission electron microscopy (HR-TEM). The glass-ceramic nature of the samples is confirmed by XRD analysis. The FTIR spectra reveal the probable stretching and bending vibration modes of silicate and phosphate groups. UV–visible absorption spectra reveal the silver embedment as Ag⁺/Ag° form in the glass matrix. Nano-size of the glass ceramics and silver nanoparticle embedment in glass matrix are confirmed by HR-TEM analysis. Dielectric spectra of samples reveal non-Debye relaxation processes. The dielectric constant of samples initially decreased and then increased with Ag₂O content. The antibacterial activities of these bioceramics were tested with different bacteria using an agar well diffusion method. Silver doped samples show good antibacterial effects without compromising the formation of hydroxyapatites. The dielectric constant of the bioglass ceramics is correlated to their antibacterial performance, with low dielectric constants giving higher antibacterial activity.     

Processing and in vitro bioactivity of high-strength 45S5 glass-ceramic scaffolds for bone regeneration

In this paper, the compressive strength and in vitro bioactivity of sintered 45S5 bioactive glass scaffolds produced by powder technology and polymer foaming were investigated. The sintering temperature of scaffolds was 975 °C. The characterization of scaffolds before immersion in SBF was performed by scanning electron microscopy (SEM) and microtomography (μCT). The scaffolds were also tested for compression, and their density and porosity were measured. After immersion, the samples were observed through SEM and analyzed using EDS, X-ray diffraction (XRD), and infrared spectroscopy (FT-IR). Mass variation was also estimated. The glass-ceramic scaffolds showed a 61.44±3.13% interconnected porosity and an average compressive strength of 13.78±2.43 MPa. They also showed the formation of a hydroxyapatite layer after seven days of immersion in SBF, demonstrating that partial crystallization during sintering did not suppress their bioactivity.