Silicate-based Bioactive Glass Research Articles

Spray-dried ternary bioactive glass microspheres: Direct and indirect structural effects of copper-doping on acellular degradation behavior

Silicate-based bioactive glass nano/microspheres hold significant promise for bone substitution by facilitating osteointegration through the release of biologically active ions and the formation of a biomimetic apatite layer. Cu-doping enhances properties such as pro-angiogenic and antibacterial behavior. While sol-gel methods usually yield homogeneous spherical particles for pure silica or binary glasses, synthesizing poorly aggregated Cu-doped ternary glass nano/microparticles without a secondary CuO crystalline phase remains challenging. This article introduces an alternative method for fabricating Cu-doped ternary microparticles using sol-gel chemistry combined with spray-drying. The resulting microspheres exhibit well-defined, poorly aggregated particles with spherical shapes and diameters of a few microns. Copper primarily integrates into the microspheres as Cu0 nanoparticles and as Cu2+ within the amorphous network. This doping affects silica network connectivity, as calcium and phosphorus are preferentially distributed in the glass network (respectively as network modifiers and formers) or involved in amorphous calcium phosphate nano-domains depending on the doping rate. These differences affect the interaction with simulated body fluid. Network depolymerization, ion release (SiO44−, Ca2+, PO43−, Cu2+), and apatite nanocrystal layer formation are impacted, as well as copper release. The latter is mainly provided by the copper involved in the silica network and not from metal nanoparticles, most of which remain in the microspheres after interaction. This understanding holds promising implications for potential therapeutic applications, offering possibilities for both short-term and long-term delivery of a tunable copper dose. Statement of significanceA novel methodology, scalable to industrial levels, enables the synthesis of copper-doped ternary bioactive glass microparticles by combining spray-drying and sol-gel chemistry. It provides precise control over the copper percentage in microspheres. This study explores the influence of synthesis conditions on the copper environment, notably Cu0 and Cu2+ ratios, characterized by EPR spectroscopy, an aspect poorly described for copper-doped bioactive glass. Additionally, copper indirectly affects silica network connectivity and calcium/phosphorus distribution, as revealed by SSNMR. Multiscale characterization illustrates how these features impact acellular degradation in simulated body fluid, highlighting the therapeutic potential for customizable copper dosing to address short- and long-term needs.

Preparation of trivalent rare-earth element-substituted bioactive glass robocast scaffolds for osteosarcoma treatment: structural, morphological, mechanical, drug delivery, and biological properties

In this study, trivalent rare-earth ion (Eu3+, Gd3+, and Yb3+)-substituted silicate-based bioactive glass scaffolds were prepared by robocasting method using sol–gel-derived bioactive glass powders for tissue engineering applications and cancer therapy. The structural, morphological, and mechanical properties of the prepared scaffolds as well as their in vitro bioactivity in simulated body fluid (SBF) were investigated in detail. In addition, an anticancer drug (5-FU) adsorption and release behavior of the scaffolds was studied as a function of time. In vitro, cytotoxicity and alkaline phosphatase activity were investigated using human skin fibroblast BJ and osteosarcoma SaOS-2 cells. Results showed that using lanthanide ion-containing (0.5, 1, 3, and 5 wt%) sol–gel-derived bioactive glass powders it was possible to successfully fabricate periodic, mesh-like patterned robocast glass scaffolds. All of the scaffolds prepared in the study sintered at 675 °C showed an amorphous structure. The compressive strength of scaffolds was in the range of 8.8 MPa to 13.6 MPa and the highest strength values were obtained in the Yb3+-containing scaffolds. Hydroxyapatite formation was obtained for the scaffolds immersed in SBF for 28 days. The fluorouracil adsorption amount was calculated to be ~ 25% for all types of scaffolds and the cumulative drug release was in the range of 20–25% depending on the dopant concentration. Results of the in vitro cell culture experiments revealed that all of the scaffolds fabricated in the study were not cytotoxic to fibroblast and osteosarcoma cells for up to 7 days under in vitro conditions. An increase was obtained for the ALP activities for both types of cells as the incubation time was increased.

Modulation of optical oxygen sensitivity of H2(TPP) by using Eu3+, Gd3+ and Yb3+ ions doped silicate-based bioactive glass powders immersed in simulated body fluid

Improving the performance of optical oxygen sensors can be accomplished by adding additives to the composition comprising an oxygen-sensitive probe encapsulated in a polymeric matrix. In this study, to advance the oxygen sensing ability, free meso-tetraphenyl porphyrin (H2(TPP)) was chosen as a luminophore. The sol-gel based 13–93 bioactive glass powders (BG) co-doped with ytterbium (Yb3+), gadolinium (Gd3+), and europium (Eu3+) and immersed in simulated body fluids (SBF) were also used as additives. After being immersed in SBF, bioactive glasses containing Eu3+, Gd3+, and Yb3+ were found to be able to convert hydroxyapatite corresponding to in vitro bioactivity tests. The optimum additive concentration for all glass samples is 3 wt%, based on photoluminescence-based properties. The luminescence dye was incorporated into poly(trimethylsilylpropyne) [poly(TMSP)] matrices in the form of a thin film along with bioactive glass additives to improve oxygen sensitivity. Emission-based intensity values of all porphyrin complexes have been followed as a signal drop during oxygen sensing measurements. The H2(TPP) along with the additive of BG:Eu3+ showed a 6.88 fold of I0/I ratio compared to the undoped and Gd3+ and Yb3+-doped BG forms in terms of the relative signal change. Large Stoke's shift (Ksv) values, high luminescence abilities, and linear spectral response make them promising candidates as oxygen sensing agents. It was concluded that prepared bioactive glass powders are suitable to use as additive materials for improving the oxygen sensitivity of meso-tetraphenyl porphyrin dye.

A Review on Three-Dimensional Printed Silicate-Based Bioactive Glass/Biodegradable Medical Synthetic Polymer Composite Scaffolds.

In recent years, tissue engineering scaffolds have turned into the preferred option for the clinical treatment of pathological and traumatic bone defects. In this field, silicate-based bioactive glasses (SBGs) and biodegradable medical synthetic polymers (BMSPs) have attracted a great deal of attention owing to their shared exceptional advantages, like excellent biocompatibility, good biodegradability, and outstanding osteogenesis. Three-dimensional (3D) printed SBG/BMSP scaffolds can not only replicate the mechanical properties and microstructure of natural bone but also degrade in situ after service and end up being replaced by regenerated bone tissue in vivo. This review first consolidates the research efforts in 3D printed SBG/BMSP scaffolds, and then focuses on their composite mechanism. This review may help to provide a fresh perspective for SBG/BMSP composite system in bone regeneration. Impact statement SBG/BMSP composites have great potential in bone tissue regeneration and repair. This article reviews the research progress of three-dimensional printed SBG/BMSP scaffolds in recent years and summarizes the composite mechanism of SBG/BMSP system in bone tissue engineering, which contributes to the development of tissue engineering scaffolds.

Electrospinning of cotton-like fibers based on cerium-doped sol–gel bioactive glass

In this study, Ce-doped calcium silicate-based bioactive glass sols were electrospun under well-defined parameters and heat-treated to obtain cotton-like fibrous structures. The 3D structures comprised long and entangled fibers with interconnected pores, and the successful incorporation of Ce was confirmed by EDX analysis. The fibers were highly hydrophilic and demonstrated in vitro bioactivity after immersion in simulated body fluid. The fibers were non-cytotoxic toward keratinocytes and did not inhibit the wound closure process, which was characterized in vitro.

An investigation on structural and in vitro biological properties of silicate-based bioactive glass powder in SiO2–CaO – P2O5–ZrO2 – Li2O quintuplet system

Zirconium (Zr) and Lithium (Li) modified 58S bioactive glasses (Z/L-BGs) were synthesized by the sol-gel method. The Z/L-BGs were immersed in simulated body fluid (SBF) solution for up to 14 days and then were assessed by structural analysis, such as Fourier transform infrared spectrum (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Moreover, pH measurements and inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis were carried out to monitor the SBF solution. The formation of hydroxyapatite (HA) on the surface after seven days of immersion was concluded from the results. Afterward, in vitro biological evaluations exhibited the stimulating impact of Z/L-BGs on the proliferation, differentiation, and viability of the MC3T3 osteoblast-like cell line. Furthermore, Z/L-BGs revealed the enhanced antibacterial efficiency against methicillin-resistant Staphylococcus Aureus (MRSA) bacteria compared to Li-free specimens.

Bioactive Properties of Composites Based on Silicate Glasses and Different Silver and Gold Structures.

Using an ideal biomaterial to treat injured bones can accelerate the healing process and simultaneously exhibit antibacterial properties; thus protecting the patient from bacterial infections. Therefore, the aim of this work was to synthesize composites containing silicate-based bioactive glasses and different types of noble metal structures (i.e., AgI pyramids, AgIAu composites, Au nanocages, Au nanocages with added AgI). Bioactive glass was used as an osteoconductive bone substitute and Ag was used for its antibacterial character, while Au was included to accelerate the formation of new bone. To investigate the synergistic effects in these composites, two syntheses were carried out in two ways: AgIAu composites were added in either one step or AgI pyramids and Au nanocages were added separately. All composites showed good in vitro bioactivity. Transformation of AgI in bioactive glasses into Ag nanoparticles and other silver species resulted in good antibacterial behavior. It was observed that the Ag nanoparticles remained in the Au nanocages, which was also beneficial in terms of antibacterial properties. The presence of Au nanoparticles contributed to the composites achieving high cell viability. The most outstanding result was obtained by the consecutive addition of noble metals into the bioactive glasses, resulting in both a high antibacterial effect and good cell viability.

Effects of Eu3+, Gd3+ and Yb3+ substitution on the structural, photoluminescence, and decay properties of silicate-based bioactive glass powders

Effects of Eu3+, Gd3+ and Yb3+ substitution on the structural, photoluminescence, and decay properties of silicate-based bioactive glass powders

Titanium-Containing Silicate-Based Sol-Gel Bioactive Glass: Development, Characterization, and Applications.

Bioactive glasses are surface-reactive glasses that, when placed in physiological fluid, undergo a transformation from glass to hydroxyapatite. Doping the bioactive glass with metallic ions can impart desirable and unique properties that are not inherent to natural hydroxyapatite. Once such ion is titanium. Titanium exists in trace amounts in native dental enamel, and its presence has been correlated with increased tooth hardness and brightness, both desirable clinical properties. Synthetic titanium-substituted hydroxyapatite exhibits better mechanical and antibacterial properties and demonstrates potential for an improved cellular response when compared to unmodified hydroxyapatite with applications in the broader field of bone tissue engineering. In this work, we use the sol-gel method to synthesize a titanium-containing silicate-based bioactive glass aimed at generating titanium-substituted hydroxyapatite on the glass surface upon immersion in body fluid. Titanium is homogeneously distributed throughout our glass, which keeps its amorphous nature. After 14 days of immersion in simulated body fluid, the glass forms a titanium-substituted hydroxyapatite on its surface. Enamel surfaces treated with the titanium-containing glass show significantly increased microhardness compared to enamel surfaces treated with a control glass, confirming the potential for the proposed glass in enamel remineralization. We also show that the presence of titanium in the glass promotes cell differentiation toward bone formation, suggesting further applications for this material in the broader field of bone tissue engineering.

Dissolution of Amorphous S53P4 Glass Scaffolds in Dynamic In Vitro Conditions.

The silicate-based bioactive glass S53P4 is clinically used in bone regenerative applications in granule form. However, utilization of the glass in scaffold form has been limited by the high tendency of the glass to crystallize during sintering. Here, careful optimization of sintering parameters enabled the manufacture of porous amorphous S53P4 scaffolds with a strength high enough for surgical procedures in bone applications (5 MPa). Sintering was conducted in a laboratory furnace for times ranging from 25 to 300 min at 630 °C, i.e., narrowly below the commencement of the crystallization. The phase composition of the scaffolds was verified with XRD, and the ion release was tested in vitro and compared with granules in continuous flow of Tris buffer and simulated body fluid (SBF). The amorphous, porous S53P4 scaffolds present the possibility of using the glass composition in a wider range of applications.

Early-Stage Dissolution Kinetics of Silicate-Based Bioactive Glass under Dynamic Conditions: Critical Evaluation.

This manuscript presents a systematic and detailed study of ion release from 45S5 bioactive glass to develop a methodology to directly monitor dissolved ions in a simulated fluid via inductively coupled plasma optical emission spectrometry (ICP OES). For the kinetic study, two dynamic tests, an inline ICP test and a flow-through test, are performed with the same flow rate, temperature, pH, ionic strength of the solution, and sample surface to leaching solution volume ratio. The flow-through test allows for the measurement of an initial dissolution rate, as well the maximum amount of any species released from the surface of the glass. In addition, the data from the inline ICP test are obtained by immediate and direct monitoring of ions from the first minutes of contact of the glass with aqueous fluids with pH values of 4 and 7.4. The overall dissolution rates of the tested commercial bioactive glass in simulated body fluid (SBF) (pH 7.4) were significantly lower compared to the initial rate acquired. The methodology developed in this study can be applied to monitor the controlled release of ions with additional therapeutic functionalities, where the amount of ions released in the first minutes can be critical for the resulting biological performance.

Erbium (III)- and Terbium (III)-containing silicate-based bioactive glass powders: physical, structural and nuclear radiation shielding characteristics

Erbium (III)- and Terbium (III)-containing silicate-based bioactive glass powders: physical, structural and nuclear radiation shielding characteristics

Sol-gel derived silicate-based bioactive glass: Studies of synergetic effect of zirconium and magnesium on structural and biological characteristics

The 5 mol.% zirconium-incorporated 58S bioactive glass (Zr-BG) was modified by addition of magnesium (Mg). These BGs were synthesizedby substitution of CaO with MgO (0, 1, 3, 5 and 7 mol.%) through the sol-gel method. The SEM, FTIR and XRD were confirmed the formation of hydroxyapatite (HA) on BGs surfaces, after 7th day of immersion in simulated body fluid (SBF) solution. The results of MTT assay and alkaline phosphatase (ALP) activity analyses showed that the specimen with 5 Zr and 5 Mg (mol.%) in composition stimulated the cell proliferation and ALP activity more than the other specimens. Mechanical properties was proved by Vickers hardness test. The ZBG-M3 and ZBG-M5 were introduced as the reliable BGs due to the best synergetic effect of both ions through in vitro evaluations and candidates for further in vivo experiments.

Phosphorous pentoxide-free bioactive glass exhibits dose-dependent angiogenic and osteogenic capacities which are retained in glass polymeric composite scaffolds.

Bioactive glasses (BGs) are attractive materials for bone tissue engineering because of their bioactivity and osteoinductivity. In this study, we report the synthesis of a novel phosphorous pentoxide-free, silicate-based bioactive glass (52S-BG) composed of 52.1% SiO2, 23.2% Na2O and 22.6% CaO (wt%). The glass was thoroughly characterized. The biocompatibility and osteogenic properties of 52S-BG particles were analyzed in vitro with human adipose-derived mesenchymal stem cells (AdMSCs) and human osteoblasts. 52S-BG particles were biocompatible and induced mineralized matrix deposition and the expression of osteogenic markers (RunX2, alkaline phosphatase, osteocalcin, osteopontin, collagen I) and the angiogenic marker vascular endothelial growth factor (VEGF). Angiogenic properties were additionally confirmed in a zebrafish embryo model. 52S-BG was added to poly-ε-caprolactone (PCL) to obtain a composite with 10 wt% glass content. Composite PCL/52S-BG scaffolds were fabricated by additive manufacturing and displayed high porosity (76%) and pore interconnectivity. The incorporation of 52S-BG particles increased the Young's modulus of PCL scaffolds from 180 to 230 MPa. AdMSC seeding efficiency and proliferation were higher in PCL/52S-BG compared to PCL scaffolds, indicating improved biocompatibility. Finally, 52S-BG incorporation improved the scaffolds' osteogenic and angiogenic properties by increasing mineral deposition and inducing relevant gene expression and VEGF protein secretion. Overall, 52S-BG particles and PCL/52S-BG composites may be attractive for diverse bone engineering applications requiring concomitant angiogenic properties.

Physical Properties and Biofunctionalities of Bioactive Root Canal Sealers In Vitro.

Calcium silicate-based bioactive glass has received significant attention for use in various biomedical applications due to its excellent bioactivity and biocompatibility. However, the bioactivity of calcium silicate nanoparticle-incorporated bioactive dental sealer is not much explored. Herein, three commercially available bioactive root canal sealers (Endoseal MTA (EDS), Well-Root ST (WST), and Nishika Canal Sealer BG (NBG)) were compared with a resin-based control sealer (AH Plus (AHP)) in terms of physical, chemical, and biological properties. EDS and NBG showed 200 to 400 nm and 100 to 200 nm nanoparticle incorporation in the SEM image, respectively, and WST and NBG showed mineral deposition in Hank’s balanced salt solution after 28 days. The flowability and film thickness of all products met the ISO 3107 standard. Water contact angle, linear dimensional changes, and calcium and silicate ion release were significantly different among groups. All bioactive root canal sealers released calcium ions, while NBG released ~10 times more silicon ions than the other bioactive root canal sealers. Under the cytocompatible extraction range, NBG showed prominent cytocompatibility, osteogenecity, and angiogenecity compared to other sealers in vitro. These results indicate that calcium silicate nanoparticle incorporation in dental sealers could be a potential strategy for dental periapical tissue regeneration.

Response of mouse bone marrow mesenchymal stem cells to graphene-containing grid-like bioactive glass scaffolds produced by robocasting.

In the study, three-dimensional, grid-like silicate-based bioactive glass scaffolds were manufactured using a robotic deposition technique. Inks were prepared by mixing 13-93 bioactive glass particles in Pluronic® F-127 solution. After deposition, scaffolds were dried at room temperature and sintered at 690°C for 1 h. The surface of the sintered scaffolds was coated with graphene nanopowder (1, 3, 5, 10 wt%) containing poly(ε-caprolactone) solution. The in vitro mineralization ability of the prepared composite scaffolds was investigated in simulated body fluid. The surface of the simulated body fluid-treated scaffolds was analyzed using scanning electron microscopy to investigate the hydroxyapatite formation. Mechanical properties were tested under compression. Results revealed that graphene coating has no detrimental effect on the hydroxyapatite forming ability of the prepared glass scaffolds. On the other hand, it decreased the compression strength of the scaffolds at high graphene concentrations. The prepared grid-like bioactive glass-based composite scaffolds did not show toxic response to bone marrow mesenchymal stem cells. It was shown that stem cells seeded onto the scaffolds attached and proliferated well on the surface. Cells seeded on the scaffolds surface also demonstrated osteogenic differentiation under in vitro conditions in the absence of transforming growth factors.

Finite element method simulation for the prediction of mechanical properties of three-dimensional periodic bioactive glass scaffolds

The desired mechanical properties of porous tissue engineering scaffolds may differ depending on the clinical applications. Therefore, it is crucial to be able to control these properties for specific cases. In the current study, cube shape, porous, silicate-based (13-93) bioactive glass scaffolds were fabricated by robotic deposition method. Scaffolds were prepared layer by layer to form constructs with a grid-like microstructure. After binder burnout, the constructs were sintered for 1 h at 700 °C to produce scaffolds consisting of dense bioactive glass struts (∼280 ± 20 μm in diameter) at different pore widths (300 ± 50, 600 ± 25, and 900 ± 50 μm). The mechanical response of the scaffolds in compression was measured experimentally. The stress analysis of the complete scaffolds with varying pore width and layer spacing parameters has been performed by finite element method (FEM) under compression to investigate the state of stress fields created within the scaffolds. Such an analysis can be used to vary several geometrical parameters and to choose the most suitable ones for the replacement of natural tissues. The compressive strengths predicted by the FEM simulations were successfully validated by comparison with experimental uniaxial compression test data, justifying the suitability of the present approach for the optimization purposes.

Bioactive Glass Fiber-Reinforced PGS Matrix Composites for Cartilage Regeneration.

Poly(glycerol sebacate) (PGS) is an elastomeric polymer which is attracting increasing interest for biomedical applications, including cartilage regeneration. However, its limited mechanical properties and possible negative effects of its degradation byproducts restrict PGS for in vivo application. In this study, a novel PGS–bioactive glass fiber (F18)-reinforced composite was developed and characterized. PGS-based reinforced scaffolds were fabricated via salt leaching and characterized regarding their mechanical properties, degradation, and bioactivity in contact with simulated body fluid. Results indicated that the incorporation of silicate-based bioactive glass fibers could double the composite tensile strength, tailor the polymer degradability, and improve the scaffold bioactivity.

Role of magnesium oxide and strontium oxide as modifiers in silicate-based bioactive glasses: Effects on thermal behaviour, mechanical properties and in-vitro bioactivity

The composition of a CaO-rich silicate bioglass (BG_Ca-Mix, in mol%: 2.3 Na2O; 2.3 K2O; 45.6 CaO; 2.6 P2O5; 47.2 SiO2) was modified by replacing a fixed 10mol% of CaO with MgO or SrO or fifty-fifty MgO-SrO. The thermal behaviour of the modified glasses was accurately evaluated via differential thermal analysis (DTA), heating microscopy and direct sintering tests. The presence of MgO and/or SrO didn't interfere with the thermal stability of the parent glass, since all the new glasses remained completely amorphous after sintering (treatment performed at 753°C for the glass with MgO; at 750°C with SrO; at 759°C with MgO and SrO). The sintered samples achieved good mechanical properties, with a Young's modulus ranging between 57.9±6.7 for the MgO-SrO modified composition and 112.6±8.0GPa for the MgO-modified one. If immersed in a simulated body fluid (SBF), the modified glasses after sintering retained the strong apatite forming ability of the parent glass, in spite of the presence of MgO and/or SrO. Moreover, the sintered glasses, tested with MLO-Y4 osteocytes by means of a multi-parametrical approach, showed a good bioactivity in vitro, since neither the glasses nor their extracts caused any negative effect on cell viability or any inhibition on cell growth. The best results were achieved by the MgO-modified glasses, both BGMIX_Mg and BGMIX_MgSr, which were able to exert a strong stimulating effect on the cell growth, thus confirming the beneficial effect of MgO on the glass bioactivity.

Microwave energy-assisted formation of bioactive CaO–MgO–SiO2 ternary glass from bio-wastes

Regeneration technique is extensively being sought after as a means of achieving bone repair without adverse immunological response. Silicate-based bioactive glasses containing Mg are gaining increasing attention for their biocompatibility. The current work has been focused on designing a facile and economic route using bio-wastes for synthesizing bioactive glasses in the CaO–MgO–SiO2 system. Rice husk ash (RHA) obtained from burning rice husk was used as silica source, while Ca was extracted from eggshells for preparing the glass through a modified sol–gel approach. The gel formed was irradiated in microwave before sintering at 950∘C for 3 h. Thereafter, bioactivity test was conducted on the samples in simulated body fluid (SBF) at physiological conditions for a maximum of 14 days. Characterization of samples were performed before and after immersion in SBF to evaluate the composition, morphology and phases present in the glass using energy-dispersive X-ray analysis, scanning electron microscopy and X-ray diffraction. Apatite formation was confirmed using Fourier transform infrared spectroscopy. Results obtained showed the presence of diopside, wollastonite and pseudo-wollastonite as major bioactive phases. Hydroxyapatite formed on the material within 3 days in SBF, indicating good bioactivity.