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Abstract Certain biomaterials are capable of inducing the secretion of Vascular Endothelial Growth Factor (VEGF) from cells exposed to their biochemical influence, which plays a vital role in stimulating angiogenesis. Looking for this capacity, in this study three porous glasses were synthesized and characterized. Glass compositions (in mol-%) were: 60SiO 2 –(36-2x)CaO–4P 2 O 5 –xCuO–xSrO with x = 0, 1 or 2.5, respectively, for B60, CuSr-1 or CuSr-2.5 glasses. Cu2+ and Sr2+ ions were added because of the reported biological capabilities of Cu2+ as angiogenic stimulator and Sr2+ as osteogenic stimulator. The objective of this study was to determine the concentration of the glass particles that, being out of the cytotoxic range, could increase VEGF secretion. The viability of cultivated bone marrow stromal cells (ST-2) was assessed. The samples were examined with light microscopy (LM) after the histochemical staining for haematoxylin and eosin (HE). The biological activity of glasses was evaluated in terms of the influence of the Cu2+ and Sr2+ ions on the cells. The dissolution products of CuSr-1 and CuSr-2.5 produced the highest secretion of VEGF from ST-2 cells after 48 h of incubation. The combination of Cu2+ and Sr2+ lays the foundation for engineering a bioactive glass than can lead to vascularized, functional bone tissue when used in bone regeneration applications. Highlights • Mesoporous bioactive glasses containing Cu and Sr synthesized. • Cytocompatibilty of glasses studied with bone marrow stromal cell line (ST-2). • Vascular Endothelial Growth Factor secretion affected by Cu and Sr release. [ABSTRACT FROM AUTHOR]

In 2005, our group described for the first time the structural characterization at the atomic scale of bioactive glasses and the influence of the glasses' nanostructure in their reactivity in simulated body fluids. In that study, two bioactive sol-gel glasses with composition 80%SiO2-20%CaO and 80%SiO2-17%CaO-3%P2O5 (in mol-%) were characterized by High-Resolution Transmission Electron Microscopy (HRTEM). Such characterization revealed unknown features of the glasses' structure at the local scale that allowed the understanding of their different in vitro behaviors as a consequence of the presence or absence of P2O5. Since then, the nanostructure of numerous bioactive glasses, including melt-prepared, sol-gel derived, and mesoporous glasses, was investigated by HRTEM, Nuclear Magnetic Resonance (NMR) spectroscopy, Molecular Dynamics (MD) simulations, and other experimental techniques. These studies have shown that although glasses are amorphous solids, a certain type of short distance order, which greatly influences the in vitro and in vivo reactivity, is always present. This paper reviews the most significant advances in the understanding of bioactive glasses that took place in the last years as a result of the growing knowledge of the glasses' nanostructure. [ABSTRACT FROM AUTHOR]

Bioactive glasses have played a very important role in the development of new materials for bone tissue regeneration. The development of new synthesis and manufacturing methods allows the preparation of bioactive glasses with new chemical compositions, nanoscaled features, customized morphologies, and pore architectures. The composition of glasses can be designed at the atomic-molecular level to ensure bioactivity and beneficial effects including capabilities for enhancing osteogenesis and vascularization or to exert bactericide action. Moreover, the glasses can be prepared as mesoporous bioactive glasses, exhibiting ordered arrangements of nanometric pores. Through the control of the microstructure, glasses can be prepared to achieve suitable interactions with living cells. Finally, the scaffolds obtained with bioactive glasses must display interconnected pores over 100 μm to make possible bone cell ingrowths and angiogenesis. In this article, the advances in the field of bioactive glasses through the control of the chemical, nanometer scale, microstructural properties, and architectural features are presented and discussed. A detailed control of these four levels of matter organization will allow optimizing the biological response of bioactive glasses when used in bone tissue regeneration. [ABSTRACT FROM AUTHOR]

3D scaffolds based in mesoporous bioactive glasses (MBGs) are being widely investigated to use in bone tissue engineering (TE) applications. These scaffolds are often obtained by rapid prototyping (RP) and exhibit an array of interconnected pores in a hierarchy of sizes. The ordered mesopore network (around 4 nm in diameter) is optimal for the adsorption and release of bone inductor biomolecules, and the arrangement of macropores over 100 μm facilitates the bone cell ingrowths and angiogenesis. Nevertheless MBG composition can be varied almost infinitely at the atomic scale by including in the glass network oxides of inorganic elements with a therapeutic action. In this article the synthesis and characterization of MBG scaffolds based on the 80%SiO 2 –15%CaO–5%P 2 O 5 (in mol-%) glass with substitutions up to 3.5% of Ga 2 O 3 or Ce 2 O 3 or 7.0% of ZnO are revisited. The substituent inclusion and the RP processing slightly decrease the surface area, the pore volume and the mesoporous order as well as their bioactive response in solutions mimicking blood plasma. However, these values still remain useful for bone TE applications. Results exhibiting the bactericide action of MBG scaffolds containing ZnO are also presented. [ABSTRACT FROM AUTHOR]

Highlights: [•] Mesoporous glasses including Ga, Ce or Zn were explored as drug delivery systems. [•] Curcumin having anticancer and other pharmacological properties was the model drug. [•] Two substituent amounts were used to know the effect on drug uptake and delivery. [•] Low substituted SiO2–CaO–P2O5 glasses released curcumin in a therapeutic range. [•] Increasing Ga, Ce or Zn caused drug retention due to interaction with substituent. [Copyright &y& Elsevier]

Throughout her impressive scientific career, Prof. María Vallet-Regí opened various research lines aimed at designing new bioceramics, including mesoporous bioactive glasses for bone tissue engineering applications. These bioactive glasses can be considered a spin-off of silica mesoporous materials because they are designed with a similar technical approach. Mesoporous glasses in addition to SiO2 contain significant amounts of other oxides, particularly CaO and P2O5 and therefore, they exhibit quite different properties and clinical applications than mesoporous silica compounds. Both materials exhibit ordered mesoporous structures with a very narrow pore size distribution that are achieved by using surfactants during their synthesis. The characteristics of mesoporous glasses made them suitable to be enriched with various osteogenic agents, namely inorganic ions and biopeptides as well as mesenchymal cells. In the present review, we summarize the evolution of mesoporous bioactive glasses research for bone repair, with a special highlight on the impact of Prof. María Vallet-Regí´s contribution to the field. [ABSTRACT FROM AUTHOR]

Bioactive glasses play an important role for the bone defects treatment. Forty years ago, it was discovered the first bioactive glass, Bioglass®, obtained by melting and used in Orthopedics and Dentistry. Twenty years ago, another family of bioactive glasses obtained by solgel processing was reported. Solgel glasses exhibit high textural properties and quicker bioactive response than melt glasses. However, their presence in the market is scarce which could be explained considering that the improvements they bring do not justify the costs of their translation to product. In the last decade, so-called template glasses exhibiting greater bioactivity than solgel glasses were described. These glasses display high pore volume and ordered mesopore structure, which makes them optimal candidates for hosting biologically active substances. For these characteristics, template glasses are being considered ideal candidates for the scaffolds manufacture used in bone engineering. This article shows the main features of three families of bioactive glasses and the importance of their nanostructure in the bioactivity. We demonstrate here that glasses with identical composition may exhibit very different properties, specifically bioactivity, as a function of their nanostructure. This fact demonstrates the importance of controlling this nanostructure in the design of new bioactive materials for bone regeneration. [ABSTRACT FROM AUTHOR]

Abstract: The in vivo evaluation, in New Zealand rabbits, of a sol–gel glass 70% CaO–30% SiO2 (in mol%) and a glass-ceramic obtained from thermal treatment of the glass, both bioactive in Kokubo''s simulated body fluid (SBF), is presented. Femoral bone diaphyseal critical defects were filled with: (i) sol–gel glass cylinders, (ii) glass-ceramic cylinders, or (iii) no material (control group). Osteosynthesis was done by means of anterior screwed plates with an associate intramedullar Kirschner wire. Each group included 10 mature rabbits, 9 months old. Follow-up was 6 months. After sacrifice, macroscopic study showed healing of bone defects, with bone coating over the cylinders, but without evidence of satisfactory repair in control group. Radiographic study showed good implant stability and periosteal growth and bone remodelling around and over the filled bone defect. The morphometric study showed minimum evidences of degradation or resorption in glass-ceramic cylinders, maintaining its original shape, but sol–gel glass cylinders showed abundant fragmentation and surface resorption. An intimate union of the new-formed bone to both materials was observed. Mechanical study showed the higher results in the glass-ceramic group, whereas sol–gel glass and control group showed no differences. The minimum degradation of glass-ceramic cylinders suggests their application in critical bone defects locations of transmission forces or load bearing. The performance of sol–gel glass cylinders suggests their usefulness in locations where a quick resorption should be preferable, considering the possibility of serving as drug or cells vehicle for both of them. [Copyright &y& Elsevier]

Mesoporous bioactive glasses (MBGs) of the SiO2–CaO–P2O5 system are biocompatible materials with a quick and effective in vitro and in vivo bioactive response. MBGs can be enhanced by including therapeutically active ions in their composition, by hosting osteogenic molecules within their mesopores, or by decorating their surfaces with mesenchymal stem cells (MSCs). In previous studies, our group showed that MBGs, ZnO-enriched and loaded with the osteogenic peptide osteostatin (OST), and MSCs exhibited osteogenic features under in vitro conditions. The aim of the present study was to evaluate bone repair capability after large bone defect treatment in distal femur osteoporotic rabbits using MBGs (76%SiO2–15%CaO–5%P2O5–4%ZnO (mol-%)) before and after loading with OST and MSCs from a donor rabbit. MSCs presence and/or OST in scaffolds significantly improved bone repair capacity at 6 and 12 weeks, as confirmed by variations observed in trabecular and cortical bone parameters obtained by micro-CT as well as histological analysis results. A greater effect was observed when OST and MSCs were combined. These findings may indicate the great potential for treating critical bone defects by combining MBGs with MSCs and osteogenic peptides such as OST, with good prospects for translation to clinical practice. [ABSTRACT FROM AUTHOR]

The increasing interest in innovative solutions for addressing bone defects has driven research into the use of Bioactive Mesoporous Glasses (MBGs). These materials, distinguished by their well-ordered mesoporous structure, possess the capability to accommodate plant extracts with well-established osteogenic properties, including bovine lactoferrin (bLF), as part of their 3D scaffold composition. This harmonizes seamlessly with the ongoing advancements in the field of biomedicine. In this study, we fabricated 3D scaffolds utilizing MBGs loaded with extracts from parsley leaves (PL) and embryogenic cultures (EC), rich in bioactive compounds such as apigenin and kaempferol, which hold potential benefits for bone metabolism. Gelatin Methacryloyl (GelMa) served as the polymer, and bLF was included in the formulation. Cytocompatibility, Runx2 gene expression, ALP enzyme activity, and biomineralization were assessed in preosteoblastic MC3T3-E1 cell cultures. MBGs effectively integrated PL and EC extracts with loadings between 22.6 ± 0.1 and 43.6 ± 0.3 µM for PL and 26.3 ± 0.3 and 46.8 ± 0.4 µM for EC, ensuring cell viability through a release percentage between 28.3% and 59.9%. The incorporation of bLF in the 3D scaffold formulation showed significant differences compared to the control in all assays, even at concentrations below 0.2 µM. Combinations, especially PL + bLF at 0.19 µM, demonstrated additive potential, with superior biomineralization compared to EC. In summary, this study highlights the effectiveness of MBGs in incorporating PL and EC extracts, along with bLF, into 3D scaffolds. The results underscore cytocompatibility, osteogenic activity, and biomineralization, offering exciting potential for future in vivo applications. [ABSTRACT FROM AUTHOR]

Beneficial effects in bone cell growth and antibacterial action are currently attributed to Ga3+ ions. Thus, they can be used to upgrade mesoporous bioactive glasses (MBGs), investigated for tissue engineering, whenever they released therapeutic amounts of gallium ions to the surrounding medium. Three gallium-enriched MBGs with composition (in mol %) xSiO2-yCaO-zP2O5-5Ga2O3, being x = 70, y = 15, z = 10 for Ga_1; x = 80, y = 12, z = 3 for Ga_2; and x = 80, y = 15, z = 0 for Ga_3, were investigated and compared with the gallium-free 80SiO2-15CaO-5P2O5 MBG (B). 29Si and 31P MAS NMR analyses indicated that Ga3+ acts as network modifier in the glass regions with higher polymerization degree and as network former in the zones with high concentration of classical modifiers (Ca2+ ions). Ga_1 and Ga_2 exhibited a quick in vitro bioactive response because they were coated by an apatite-like layer after 1 and 3 days in simulated body fluid. Although we have not conducted biological tests in this paper (cells or bacteria), Ga_1 released high but non-cytotoxic amounts of Ga3+ ions in Todd Hewitt Broth culture medium that were 140 times higher than the IC90 of Pseudomonas aeruginosa bacteria, demonstrating its potential for tissue engineering applications. [ABSTRACT FROM AUTHOR]

In search of new approaches to treat bone infection and prevent drug resistance development, a nanosystem based on hollow bioactive glass nanoparticles (HBGN) of composition 79.5SiO2-(18-x)CaO-2.5P2O5-xCuO (x = 0, 2.5 or 5 mol-% CuO) was developed. The objective of the study was to evaluate the capacity of the HBGN to be used as a nanocarrier of the broad-spectrum antibiotic danofloxacin and source of bactericidal Cu2+ ions. Core-shell nanoparticles with specific surface areas close to 800 m2/g and pore volumes around 1 cm3/g were obtained by using hexadecyltrimethylammonium bromide (CTAB) and poly(styrene)-block-poly(acrylic acid) (PS-b-PAA) as structure-directing agents. Flow cytometry studies showed the cytocompatibility of the nanoparticles in MC3T3-E1 pre-osteoblastic cell cultures. Ion release studies confirmed the release of non-cytotoxic concentrations of Cu2+ ions within the therapeutic range. Moreover, it was shown that the inclusion of copper in the system resulted in a more gradual release of danofloxacin that was extended over one week. The bactericidal activity of the nanosystem was evaluated with E. coli and S. aureus strains. Nanoparticles with copper were not able to reduce bacterial viability by themselves and Cu-free HBGN failed to reduce bacterial growth, despite releasing higher antibiotic concentrations. However, HBGN enriched with copper and danofloxacin drastically reduced bacterial growth in sessile, planktonic and biofilm states, which was attributed to a synergistic effect between the action of Cu2+ ions and danofloxacin. Therefore, the nanosystem here investigated is a promising candidate as an alternative for the local treatment of bone infections. [ABSTRACT FROM AUTHOR]

The in vivo evaluation, in New Zealand rabbits, of a SiO2–P2O5–CaO sol–gel glass and a SiO2–P2O5–CaO–MgO glass-ceramic, both bioactive in Kokubo''s simulated body fluid (SBF), is presented. Bone defects, performed in the lateral aspect of distal right femoral epiphysis, 5 mm in diameter and 4 mm in depth, were filled with (i) sol–gel glass disks, (ii) glass-ceramic disks, or (iii) no material (control group). Each group included 8 mature and 8 immature rabbits. A 4-month radiographic study showed good implant stability without axial deviation of extremities in immature animals and periosteal growth and remodelling around and over the bone defect. After sacrifice, the macroscopic study showed healing of bone defects, with bone coating over the implants. The morphometric study showed a more generous bone formation in animals receiving sol–gel glass or glass-ceramic disks than in control group. Histomorphometric study showed an intimate union of the new-formed bone to the implants. This study allows considering both materials as eligible for bone substitution or repair. Their indications could include cavities filling and the coating of implant surfaces. The minimum degradation of glass-ceramic disks suggests its application in locations of load or transmission forces. As specific indication in growth plate surgery, both materials could be used as material of interposition after bony bridges resection. [Copyright &y& Elsevier]

The biocompatibility of three sol–gel bioactive glasses with SiO2 as the main constituent (75, 72.5 and 70 mol%), identical CaO content (25 mol%), and without or with P2O5 as third constituent (0, 2.5 and 5 mol%), have been analyzed (S75, S72.5P2.5, and S70P5 glasses). These studies were performed on both untreated glasses and on glasses coated with a hydroxycarbonate apatite (HCA) layer formed in vitro by soaking 7 d in an acellular simulated body fluid. Cell attachment, spreading and proliferation were studied using neonatal rat calvaria osteoblasts. Cells attach to the three untreated glasses but show a higher efficiency on that with the higher phosphate content (S70P5). The formation of the HCA layer significantly enhances this process (1.7-fold). In all cases, attachment is followed by cell spreading on the surface of the materials, adopting the cells a flattened morphology and showing diverse anchoring cell projections. Mitotic activity has been detected on osteoblasts growing on the sol–gel glasses, being this process 2–4-fold higher when the apatite-like layer is already formed. Taking into account the results herein presented, these bioactive glasses can be considered biocompatible. In addition, their biocompatibility is greatly enhanced after induction of the formation of an HCA layer. [Copyright &y& Elsevier]

Mesoporous Bioactive Glasses (MBGs) are a family of bioceramics widely investigated for their putative clinical use as scaffolds for bone regeneration. Their outstanding textural properties allow for high bioactivity when compared with other bioactive materials. Moreover, their great pore volumes allow these glasses to be loaded with a wide range of biomolecules to stimulate new bone formation. In this study, an MBG with a composition, in mol%, of 80% SiO2-15% CaO-5% P2O5 (Blank, BL) was compared with two analogous glasses containing 4% and 5% of ZnO (4ZN and 5ZN) before and after impregnationwith osteostatin, a C-terminal peptide froma parathyroid hormone-related protein (PTHrP107-111). Zn2+> ions were included in the glass for their bone growth stimulator properties, whereas osteostatin was added for its osteogenic properties. Glasses were characterized, and their cytocompatibility investigated, in pre-osteoblastic MC3T3-E1 cell cultures. The simultaneous additions of osteostatin and Zn2+> ions provoked enhanced MC3T3-E1 cell viability and a higher differentiation capacity, compared with either raw BL or MBGs supplemented only with osteostatin or Zn2+>. These in vitro results show that osteostatin enhances the osteogenic effect of Zn2+>-enriched glasses, suggesting the potential of this combined approach in bone tissue engineering applications. [ABSTRACT FROM AUTHOR]

Polypill is a medication designed for preventing heart attacks through a combination of drugs. Current formulations contain blood pressure-lowering drugs and others, such statins or acetylsalicylic acid. These drugs exhibit different physical chemical features, and consequently different release kinetics. Therefore, the concentration in plasma of some of them after the release process can be out of the therapeutic range. This paper investigates a new methodology for the control dosage of a polypill recently reported containing hydrochlorothiazide, amlodipine, losartan and simvastatin in a 12.5/2.5/25/40 weight ratio. The procedure is based on mesoporous silica nanoparticles (MSN) with MCM-41 structure (MSN-41) used as carrier, aimed to control release of the four drugs included in the polypill. In vitro release data were obtained by HPLC and the curves adjusted with a kinetic model. To explain the release results, a molecular model was built to determine the drug-matrix interactions, and quantum mechanical calculations were performed to obtain the electrostatic properties of each drug. Amlodipine, losartan and simvastatin were released from the polypill-MSN-41 system in a controlled way. This would be a favourable behavior when used clinically because avoid too quick pressure decrease. However, the diuretic hydrochlorothiazide was quickly released from our system in the first minutes, as is needed in hypertensive urgencies. In addition, an increase in the stability of amlodipine and hydrochlorothiazide occurred in the polypill-MSN-41 system. Therefore, the new way of polypill dosage proposed can result in a safer and effective treatment. [ABSTRACT FROM AUTHOR]

Ion-doped binary SiO 2 -CaO and ternary SiO 2 -CaO-P 2 O 5 mesoporous bioactive glasses were synthesized and characterized to evaluate the influence of P 2 O 5 in the glass network structure. Strontium, copper and cobalt oxides in a proportion of 0.8 mol% were selected as dopants because the osteogenic and angiogenic properties reported for these elements. Although the four glass compositions investigated presented analogous textural properties, TEM analysis revealed that the structure of those containing P 2 O 5 exhibited an increased ordered mesoporosity. Furthermore, 29 Si NMR revealed that the incorporation of P 2 O 5 increased the network connectivity and that this compound captured the Sr 2 + , Cu 2 + and Co 2 + ions preventing them to behave as modifiers of the silica network. In addition, 31 P NMR results revealed that the nature of the cation directly influences the characteristics of the phosphate clusters. In this study, we have proven that phosphorous oxide entraps doping-metallic ions, granting these glasses with a greater mesopores order. [ABSTRACT FROM AUTHOR]

Highlights: [•] A molecular model was built to explain the controlled release from SBA-15. [•] When SBA-15 was modified with APTES the release kinetics greatly decreased. [•] Molecular modelling gave similar interaction energies before and after functionalizing. [•] The interaction of amino groups of APTES and SBA-15 notably distorts the pores. [•] This distortion explains the retarded release of the model drug from SBA-15-APTES. [Copyright &y& Elsevier]

Abstract: Parathyroid hormone-related protein (PTHrP) is an important regulator of bone formation and remodeling. Our recent findings demonstrate that PTHrP (107–111) (osteostatin) loaded onto silica-based ordered mesoporous SBA15 materials exhibit osteogenic features in osteoblastic cell cultures. We aimed here to elucidate whether these peptide-coated materials might be suitable for promoting bone repair following a cavitary defect in the rabbit femur. Histological examination revealed the absence of significant inflammation or bone resorption within the time of study (4 and 8 weeks) after implantation. At 8 weeks, the peptide-unloaded materials were still separated from the bone marrow by a fibrous cap, which was greatly diminished by the presence of the PTHrP peptide. By using μCT analysis, new bone formation was evident at different distances from the implants, mainly for the latter peptide-loaded biomaterials. This was confirmed by performing immunostaining for different osteoblast markers. Our findings demonstrate that these PTHrP (107–111)-loaded bioceramics significantly improve local bone induction, as compared to that observed with the unloaded material. [ABSTRACT FROM AUTHOR]

Abstract: SBA-15 was investigated for the controlled release of vancomycin. The kinetic of release drastically changed after functionalizing the mesoporous material with octyltrimethoxysilane (C8) chains. That way, the kinetic constant of release decreased from 0.890min−1/2, for pure SBA-15, to 0.068min−1/2, for C8-SBA-15. This variation was explained by using, for the first time, molecular modelling and docking. The studies showed the low compatibility between the electrostatic potentials of a pure silica mesoporous model and the vancomycin molecule, because both are essentially negative. However, a model including C8 alkyl chains exhibited a stronger interaction with the drug by weakening the negative surface charge of SBA-15. Furthermore, docking showed that the drug molecules were not able to penetrate into the channels, except the small positive head of vancomycin that interacts with the matrix partially blocking the pores. A strong correlation between the theoretical calculations and the experimental data was established; showing the potentiality of molecular modelling in the design of controlled release devices based in SBA-15 and analogous systems. [Copyright &y& Elsevier]

Hybrid scaffolds based on bioactive glass (BAG) particles (<38 µm), covalently linked to gelatin (G*) using 3-glycidoxypropyltrimethoxysilane (GPTMS), have been studied for bone bioengineering. In this study, two glass compositions (13-93 and 13-93B20 (where 20% of the SiO2 was replaced with B2O3)) were introduced in the gelatin matrix. The Cfactor (gelatin/GPTMS molar ratio) was kept constant at 500. The hybrids obtained were found to be stable at 37 °C in solution, the condition in which pure gelatin is liquid. All hybrids were characterized by in vitro dissolution in Tris(hydroxymethyl)aminomethane (TRIS) solution (for up to 4 weeks) and Simulated Body Fluid (SBF) (for up to 2 weeks). Samples processed with 13-93B20 exhibited faster initial dissolution and significantly faster precipitation of a hydroxyapatite (HA) layer. The faster ion release and HA precipitation recorded from the G*/13-93B20 samples are attributable to the higher reactivity of borosilicate compared to silicate glass. The MC3T3-E1 cell behavior in direct contact with the hybrids was investigated, showing that the cells were able to proliferate and spread on the developed biomaterials. Tailoring the glass composition allows us to better control the material's dissolution, biodegradability, and bioactivity. Bioactive (especially with 13-93B20 BAG) and biocompatible, the hybrids are promising for bone application. [ABSTRACT FROM AUTHOR]

In the search of a new biomaterial for the treatment of bone defects resulting from traumatic events, an osteoporosis scenario with bone fractures, tumor removal, congenital pathologies or implant revisions for infection, we developed 3D scaffolds based on mesoporous bioactive glasses (MBGs) (85 − x)SiO2–5P2O5–10CaO–xSrO (x = 0, 2.5 and 5 mol.%). The scaffolds with meso-macroporosity were fabricated by pouring a suspension of MBG powders in polyvinyl alcohol (PVA) into a negative template of polylactic acid (PLA), followed by removal of the template by extraction at low temperature. SrO-containing MBGs exhibited excellent properties for bone substitution including ordered mesoporous structure, high textural properties, quick in vitro bioactive response in simulated body fluid (SBF) and the ability of releasing concentrations of strontium ions able to stimulate expression of early markers of osteoblastic differentiation. Moreover, the direct contact of MC3T3-E1 pre-osteoblastic cells with the scaffolds confirmed the cytocompatibility of the three compositions investigated. Nevertheless, the scaffold containing 2.5% of SrO induced the best cellular proliferation showing the potential of this scaffold as a candidate to be further investigated in vitro and in vivo, aiming to be clinically used for bone regeneration applications in non-load bearing sites. [ABSTRACT FROM AUTHOR]