Mesoporous Bioactive Glass Nanospheres Research Articles

Facile synthesis, characterization, biocompatibility and protein loading/release property of zinc-doped hollow mesoporous bioactive glass nanospheres

Facile synthesis, characterization, biocompatibility and protein loading/release property of zinc-doped hollow mesoporous bioactive glass nanospheres

Fabrication and characterization of novel ZnO-loaded mesoporous bioactive glass nanospheres with enhanced physiochemical properties and biocompatibility for bone tissue engineering

Novel ZnO-modified mesoporous bioactive glass nanospheres (MBNs) were developed by a modified sol-gel method and their physiochemical behavior and cytocompatibility were systematically evaluated. Compared to previous researches, an offered synthesis method resulted in much less compositional deviation between the nominal and real compositions, while retaining spherical shape and dispersion of the nanoparticles. The MBNs exhibited a higher specific surface area (280–343 m2/g) and a larger pore volume than various ZnO-loaded bioactive glasses prepared before. In contrast to most mesoporous bioceramics doped with ZnO, the current nanoparticles revealed an excellent bioactivity within 14 days immersion in simulated body fluid (SBF). Furthermore, an optimum ZnO content for enhanced viability of bone marrow mesenchymal stem cells cultured with ionic extracts of the nanoparticles is 0.5%. Thanks to a high particle dispersion, good textural properties, bioactivity, and high cytocompatibility, the prepared nanoparticles can be recommended as promising filler materials dental/bone tissue engineering.

Improved Osseointegration of Selective Laser Melting Titanium Implants with Unique Dual Micro/Nano-Scale Surface Topography.

Selective laser melting manufacture of patient specific Ti implants is serving as a promising approach for bone tissue engineering. The success of implantation is governed by effective osseointegration, which depends on the surface properties of implants. To improve the bioactivity and osteogenesis, the universal surface treatment for SLM-Ti implants is to remove the primitive roughness and then reengineer new roughness by various methods. In this study, the micro-sized partially melted Ti particles on the SLM-Ti surface were preserved for assembling mesoporous bioactive glass nanospheres to obtain a unique micro/nano- topography through combination of SLM manufacture and sol-gel processes. The results of simulated body fluid immersion test showed that bioactive ions (Ca, Si) can be continuously and stably released from the MBG nanospheres. The osseointegration properties of SLM-Ti samples, examined using pre-osteoblast cells, showed enhanced adhesion and osteogenic differentiation compared with commercial pure titanium commonly used as orthopedic implants. Overall, the developed approach of construction of the dual micro/nano topography generated on the SLM-Ti native surface could be critical to enhance musculoskeletal implant performance.

Using Copper-Doped Mesoporous Bioactive Glass Nanospheres to Impart Anti-Bacterial Properties to Dental Composites.

Experimental dental resin composites containing copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were developed to impart anti-bacterial properties. Increasing amounts of Cu-MBGN (0, 1, 5 and 10 wt%) were added to the BisGMA/TEGDMA resin matrix containing micro- and nano-fillers of inert glass, keeping the resin/filler ratio constant. Surface micromorphology and elemental analysis were performed to evaluate the homogeneous distribution of filler particles. The study investigated the effects of Cu-MBGN on the degree of conversion, polymerization shrinkage, porosity, ion release and anti-bacterial activity on S. mutans and A. naeslundii. Experimental materials containing Cu-MBGN showed a dose-dependent Cu release with an initial burst and a further increase after 28 days. The composite containing 10% Cu-MBGN had the best anti-bacterial effect on S. mutans, as evidenced by the lowest adherence of free-floating bacteria and biofilm formation. In contrast, the 45S5-containing materials had the highest S. mutans adherence. Ca release was highest in the bioactive control containing 15% 45S5, which correlated with the highest number of open porosities on the surface. Polymerization shrinkage was similar for all tested materials, ranging from 3.8 to 4.2%, while the degree of conversion was lower for Cu-MBGN materials. Cu-MBGN composites showed better anti-bacterial properties than composites with 45S5 BG.

Enhanced biological behavior and antibacterial property of WS2 nanosheets modified mesoporous bioactive glass nanospheres for bone tissue engineering

Mesoporous bioactive glasses (MBGs) are deemed as bone implants for inducing osteoblast differentiation and preventing bone resorption, however, the damage of peri-implantitis on soft and bone tissue has been generally overlooked. To overcome the significant antibacterial deficiency of MBGs, the tungsten disulfide (WS2) nanosheets as near-infrared (NIR) photothermal agents have been integrated with MBG nanospheres to develop novel multifunctional WS2/MBG nanocomposites in this work. The results show that all the WS2/MBG nanocomposites exhibit mesoporous structures with larger specific surface area (up to 475.35 m2/g)) and more negative surface zeta potential (−17.4 mV) than MBG. Notably, the WS2/MBG nanocomposites can effectively promote the apatite forming ability, the proliferation and viability of MC3T3-E1 cells, as well as up-regulate the osteogenic related genes expression of Alp, Runx2, Col1a1, Opn and Bglap. Moreover, it is highlighted that the WS2/MBG nanocomposites exhibit excellent antibacterial efficacy toward S. aureus under NIR laser irradiation, with the antibacterial rate up to 96.13%. These results will offer an appealing strategy to develop multifunctional WS2/MBG nanocomposites with enhanced biological activity and additional antibacterial property for bone tissue engineering.

Impact of Copper-Doped Mesoporous Bioactive Glass Nanospheres on the Polymerisation Kinetics and Shrinkage Stress of Dental Resin Composites.

We embedded copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) with antibacterial and ion-releasing properties into experimental dental composites and investigated the effect of Cu-MBGN on the polymerisation properties. We prepared seven composites with a BisGMA/TEGDMA (60/40) matrix and 65 wt.% total filler content, added Cu-MBGN or a combination of Cu-MBGN and silanised silica to the silanised barium glass base, and examined nine parameters: light transmittance, degree of conversion (DC), maximum polymerisation rate (Rmax), time to reach Rmax, linear shrinkage, shrinkage stress (PSS), maximum PSS rate, time to reach maximum PSS rate, and depth of cure. Cu-MBGN without silica accelerated polymerisation, reduced light transmission, and had the highest DC (58.8 ± 0.9%) and Rmax (9.8 ± 0.2%/s), but lower shrinkage (3 ± 0.05%) and similar PSS (0.89 ± 0.07 MPa) versus the inert reference (0.83 ± 0.13 MPa). Combined Cu-MBGN and silica slowed the Rmax and achieved a similar DC but resulted in higher shrinkage. However, using a combined 5 wt.% Cu-MBGN and silica, the PSS resembled that of the inert reference. The synergistic action of 5 wt.% Cu-MBGN and silanised silica in combination with silanised barium glass resulted in a material with the highest likelihood for dental applications in future.

Research on rare earth doped mesoporous bioactive glass nanospheres. Ⅰ. Similarity of in vitro biological effects

Rare earth (RE) elements, known as “industrial vitamins,” are widely used in advanced materials to optimize their properties. In this work, RE (La, Ce, Pr, Nd, Eu and Dy)-doped mesoporous bioactive glass nanospheres (RE/MBG) were synthesized using the sol-gel method. It was proven for the first time that the homology of RE ions confers functional similarity in bone tissue engineering, and the desired properties are obtained by guiding cell behavior and changing the physicochemical properties of biomaterials. It was found that RE/MBG nanospheres have similar structures and therefore similar properties, such as sustained drug release and anticancer prope dy provides a feasible strategy for the development, evaluation and basic research of homologous group ion-doped nanobiomaterials in bone tissue engineering.

Effect of nitrogen on the structure evolution and biological properties of mesoporous bioactive glass nanospheres: Experiments and simulations

Mesoporous bioactive glasses (MBGs) have displayed great potential in dental restorations and bone regeneration for their controllable structure and great bioactivity. In this work, we have systematically investigated the effect of nitrogen on structure evolution, apatite-forming ability and cytotoxicity in MBG by successfully preparing the N-containing MBG nanospheres by a modified sol-gel method. It is interesting to demonstrate that all obtained samples exhibit uniform interstitial mesoporous nanospheres microstructure, with the particles size increases as the nitrogen addition increases from 5 to 15 mol.%. Notably, a large amount of blooming flower-like hydroxyapatite deposited on the surface of 15N-MBG after immersed in simulated body fluid for 7 days, exhibiting excellent apatite-forming ability. It is highlighted that the incorporation of nitrogen can stimulate cell proliferation at early incubation time. Moreover, all the MBGs have no obvious inhibitory impact on the hPDLCs growth at extracted concentration. Furthermore, via glass network connectivity analysis from molecular dynamics simulations, the decrease of network connectivity caused by the incorporation of nitrogen could provide looser glass network and higher bioactivity, which explains the experimental results well.

Facile fabrication of hollow mesoporous bioactive glass spheres: From structural behaviour to in vitro biology evaluation

Bone defects accompanied by infection or inflammation can significantly delay the healing process. To simultaneously achieve controlled release of local antibiotics for infection control and bone healing, bone-implantable delivery systems have been considered as a promising strategy. This study aims to improve drug loading capacity of bone-implantable delivery systems by introducing hollow structure mesoporous bioactive glass nanospheres (HMBGs) through a sol–gel process. Particularly, such core–shell bimodal-porous structured nanoparticles were prepared through a sacrificing template using cetyltrimethylammonium bromide (CTAB) as surfactant. It was found that varying the amount of CTAB during the synthesis process is a simple and effective approach for tuning the particle size, morphology, and structure of HMBGs. For in vitro drug release, HMBGs could sustain storage and release of vancomycin hydrochloride (VAN) via diffusion-controlled mechanism, thereby inhibiting the bacteria growth in the subsequent bacterial study. Moreover, HMBGs incorporated with VAN provided a biomimetic microenvironment favored by cell adhesion and proliferation. These findings support the compatibility of HMBG nanoparticles with antibiotics and their potential application in the treatment of infectious bone defects.

Sol-gel synthesis and characterization of novel cobalt ions-containing mesoporous bioactive glass nanospheres as hypoxia and ferroptosis-inducing nanotherapeutics

Herein, novel Co2+ ions-containing mesoporous bioactive glass nanospheres (Co-BGn) with low and high cobalt contents were prepared by a facile one-pot ultrasonic-coupled sol-gel synthesis. Structural evaluations revealed that Co-BGn are totally amorphous and cobalt ions exist as Co2+ ions in the glass structure. Notably, Co-BGn exhibited uniform spherical morphology, nanosize (< 100 nm), high worm-like mesoporosity (0.41 cm3/g) and large specific surface area ca. 787.5 m2/g. Interestingly, low and high Co-BGn showed sustained release of Co2+ ions with controlled release (8 – 32 ppm) and fast release (54 – 112.5 ppm) kinetics over 2 weeks, respectively. Furthermore, Co-BGn showed good bone-like hydroxyapatite formation in vitro. Accordingly, low Co-BGn with controlled release of Co2+ ions can be considered as hypoxia-mimic nanotherapeutics for bone/skin tissue regeneration. Whereas, high Co-BGn with fast release of high concentrations of Co2+ ions can be considered for ferroptosis killing of cancer cells including bone and skin cancers.

Preparation and osteogenic properties of nanocomposite hydrogel beads loaded with nanometric bioactive glass particles

Bone reconstruction in the oral and maxillofacial region presents particular challenges related to the development of biomaterials with osteoinductive properties and suitable physical characteristics for their surgical use in irregular bony defects. In this work, the preparation and bioactivity of chitosan–gelatin (ChG) hydrogel beads loaded with either bioactive glass nanoparticles (nBG) or mesoporous bioactive glass nanospheres (nMBG) were studied. In vitro testing of the bionanocomposite beads was carried out in simulated body fluid, and through viability and osteogenic differentiation assays using dental pulp stem cells (DPSCs). In vivo bone regenerative properties of the biomaterials were assessed using a rat femoral defect model and compared with a traditional maxillary allograft (Puros®). ChG hydrogel beads containing homogeneously distributed BG nanoparticles promoted rapid bone—like apatite mineralization and induced the osteogenic differentiation of DPSCs in vitro. The bionanocomposite beads loaded with either nBG or nMBG also produced a greater bone tissue formation in vivo as compared to Puros® after 8 weeks of implantation. The osteoinductivity capacity of the bionanocomposite hydrogel beads coupled with their physical properties make them promissory for the reconstruction of irregular and less accessible maxillary bone defects.

Incorporation of Copper-Doped Mesoporous Bioactive Glass Nanospheres in Experimental Dental Composites: Chemical and Mechanical Characterization.

Experimental dental resin composites incorporating copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) were designed to impart antibacterial and remineralizing properties. The study evaluated the influence of Cu-MBGN on the mechanical properties and photopolymerization of resin composites. Cu-MBGN were synthesized using a microemulsion-assisted sol–gel method. Increasing amounts of Cu-MBGN (0, 1, 5, and 10 wt %) were added to the organic polymer matrix with inert glass micro- and nanofillers while maintaining a constant resin/filler ratio. Six tests were performed: X-ray diffraction, scanning electron microscopy, flexural strength (FS), flexural modulus (FM), Vickers microhardness (MH), and degree of conversion (DC). FS and MH of Cu-MBGN composites with silica fillers showed no deterioration with aging, with statistically similar results at 1 and 28 days. FM was not influenced by the addition of Cu-MBGN but was reduced for all tested materials after 28 days. The specimens with 1 and 5% Cu-MBGN had the highest FS, FM, MH, and DC values at 28 days, while controls with 45S5 bioactive glass had the lowest FM, FS, and MH. DC was high for all materials (83.7–93.0%). Cu-MBGN composites with silica have a potential for clinical implementation due to high DC and good mechanical properties with adequate resistance to aging.

Design of poly-l-glutamic acid embedded mesoporous bioactive glass nanospheres for pH-stimulated chemotherapeutic drug delivery and antibacterial susceptibility

In this research, a core-shell type pH-responsive poly-l-glutamic acid embedded mesoporous bioactive glass nanospheres (MBAG/PLGA) was designed via aminosilane functionalization of MBAG using 3-aminopropyltriethoxysilane (APTES). The formation of MBAG/PLGA was well dispersed in an aqueous medium and demonstrated high drug loading efficacy and enhanced drug delivery rate. Daunomycin (DAN) was considered as a model chemotherapeutic drug for loading and release study. The cumulative in vitro release of DAN from DAN loaded MBAG/PLGA (MBAG/PLGA@DAN) was observed to be pH-dependent and, the DAN release rate was much higher at pH ∼ 5.5 compared to pH at 7.4. The modified Kirby-Bauer microbial assay results showed that the MBAG is a potential antimicrobial agent and susceptibility for Gram-negative bacteria is observed to be much higher than Gram-positive ones. Advanced characterization studies such as SEM coupled with EDX, HRTEM, FTIR, XPS, TGA, XRD, and BET analysis were performed to support the findings of this research. Overall, these results demonstrated that MBAG/PLGA is a promising candidate for a pH-responsive localized drug delivery system in bioconjugate science.

Effect of B2O3 on the structural and in vitro biological assessment of mesoporous bioactive glass nanospheres

AbstractIn this paper, the boron‐containing mesoporous bioactive glass (MBG) nanospheres have been successfully synthesized by modified sol‐gel method assisted by surfactant, and the effect of boron substitution on structure and bioactivity was evaluated by combining experiments and ab initio molecular dynamics (AIMD) simulations. All of the samples exhibit regularly uniform mesoporous spherical microstructure with an average size of about 60 nm, and the boron‐containing MBGs show higher specific surface area with the value up to 416.20 m2/g. The simulated body fluid (SBF) immersion test confirms that the deposited hydroxyapatite (HA) evidently increases with the increasing of boron content, indicating that the biological behavior has been significantly improved resulting from incorporation of boron. Additionally, our results also reveal that B2O3 substitution has positive impact on cell proliferation of human periodontal ligament cells (hPDLCs) at lower extracted concentration. Furthermore, AIMD simulation is employed to understand the relationship between structural changes and in vitro bioactivity in terms of structural information, especially the boron coordination number. The results illustrate that the boron‐containing MBG nanospheres with excellent bioactivity are great potential for biomedical applications.

An Immunological Approach to the Biocompatibility of Mesoporous SiO2-CaO Nanospheres.

Mesoporous bioactive glass nanospheres (NanoMBGs) have high potential for clinical applications. However, the impact of these nanoparticles on the immune system needs to be addressed. In this study, the biocompatibility of SiO2-CaO NanoMBGs was evaluated on different mouse immune cells, including spleen cells subsets, bone marrow-derived dendritic cells (BMDCs), or cell lines like SR.D10 Th2 CD4+ lymphocytes and DC2.4 dendritic cells. Flow cytometry and confocal microscopy show that the nanoparticles were rapidly and efficiently taken up in vitro by T and B lymphocytes or by specialized antigen-presenting cells (APCs) like dendritic cells (DCs). Nanoparticles were not cytotoxic and had no effect on cell viability or proliferation under T-cell (anti-CD3) or B cell (LPS) stimuli. Besides, NanoMBGs did not affect the balance of spleen cell subsets, or the production of intracellular or secreted pro- and anti-inflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-6, IL-10) by activated T, B, and dendritic cells (DC), as determined by flow cytometry and ELISA. T cell activation surface markers (CD25, CD69 and Induced Costimulator, ICOS) were not altered by NanoMBGs. Maturation of BMDCs or DC2.4 cells in vitro was not altered by NanoMBGs, as shown by expression of Major Histocompatibility Complex (MHC) and costimulatory molecules (CD40, CD80, CD86), or IL-6 secretion. The effect of wortmannin and chlorpromazine indicate a role for phosphoinositide 3-kinase (PI3K), actin and clathrin-dependent pathways in NanoMBG internalization. We thus demonstrate that these NanoMBGs are both non-toxic and non-inflammagenic for murine lymphoid cells and myeloid DCs despite their efficient intake by the cells.

Synthesis and characterization of novel mesoporous strontium-modified bioactive glass nanospheres for bone tissue engineering applications

Abstract Mesoporous bioactive glass nanoparticles (MBNs) have recently gained increasing attention as nanocarriers for co-delivery of therapeutic ions and molecules for treatment of hard tissue injuries. In the current study, novel Sr-substituted silica-based MBNs were synthesized through a template assisted sol-gel process. The results showed that the prepared nanoparticles are amorphous with a spherical morphology and an average size between 86 and 115 nm, and their microstructure is not considerably changed by Sr incorporation. The produced nanoparticles have a disordered mesoporous structure and notably better dispersion, as well as higher textural properties including specific surface area (408–480 m2/g) and pore volume (0.54–0.62 cm3/g), compared to most Sr-modified mesoporous bioactive glasses synthesized to date. In-vitro mineralization experiments revealed that the synthesized nanospheres exhibit an excellent bioactivity within 3 days immersion in simulated body fluid (SBF) solution, irrespective of the Sr content. Moreover, the prepared nanospheres are ideal platforms for a sustained release of ibuprofen in SBF up to 7 days. In-vitro cell viability results proved that the ionic extracts of the Sr-loaded MBNs can markedly increase the proliferation of adipose tissue-derived stem cells (ADSCs), and Wharton's jelly-derived stem cells (WJSCs) compared to the performance of unloaded MBNs, at certain concentrations. Due to the spherical shape, excellent dispersion and promising physiochemical/biological properties, the newly synthesized Sr-loaded MBNs are encouraging filler materials for fabrication of nanocomposite scaffolds for treatment of bone defects.

Design and Evaluation of Europium Containing Mesoporous Bioactive Glass Nanospheres: Doxorubicin Release Kinetics and Inhibitory Effect on Osteosarcoma MG 63 Cells.

Functional ions and drug factors play a vital role in stimulating bone tissue regeneration as we understand it. In this work, europium-containing mesoporous bioactive glass nanospheres (Eu/MBGs), composed of 60% SiO2—(36–x)%CaO—x%Eu2O3—4%P2O5 (x = 0, 0.5, 1, 2 mol%), were prepared by a facile sol-gel process. The results indicate that Eu ions play an important role to influence the microstructure of MBGs, in which a suitable concentration of Eu (1 mol%) increases their surface area (502 m2/g) as well as their pore volume (0.34 cm3/g). Proper doping of Eu ions in MBGs can observably induce apatite mineralization and improve the doxorubicin (DOX) release behavior. Furthermore, DOX-loaded Eu/MBGs could maintain a long-term inhibitory effect on the viability of osteosarcoma MG 63 cells. This work has demonstrated that it is possible to develop functional Eu/MBGs by combining excellent apatite-mineralization ability, controllable drug (DOX) release and antitumor functions for the therapy of bone tissue regeneration.

Dual-Functional Dendritic Mesoporous Bioactive Glass Nanospheres for Calcium Influx-Mediated Specific Tumor Suppression and Controlled Drug Delivery in Vivo.

The development of nanomaterials for stable, controlled delivery of drugs and efficient suppression of tumor growth with desirable biosafety remains challenging in the nano-biomedical field. In this study, we prepared and optimized mesoporous bioactive glass (MBG) nanospheres to establish a functional drug delivery system and analyzed the effect of the dendritic mesoporous structure on drug loading and release. We then utilized an in vitro model to examine the biological effects of dendritic MBG nanospheres on normal and tumor cells and studied the molecular mechanism underlying specific tumor suppression by MBG nanospheres. Finally, we investigated the combinational effect of MBG nanospheres and a cancer therapeutic drug with an in vivo tumor xenograft model. Our results show that the dendritic MBG nanospheres have been successfully synthesized by optimizing calcium: silicon ratio. MBG nanospheres exhibit a dendritic mesoporous structure with a large specific surface area, demonstrate high drug loading efficiency, and release drugs in a controlled fashion to effectively prolong drug half-life. Ca2+ in nanospheres activates transient receptor potential channels and calcium-sensing receptor on tumor cells, mediates calcium influx, and directly regulates the calpain-1-Bcl-2-caspase-3 signaling pathway to specifically suppress tumor growth without affecting normal cells. In addition, dendritic MBG nanospheres synergize with cancer drugs to improve antitumor efficacy and reduce systemic toxicity. Dendritic MBG nanospheres with antitumor activity and controlled drug release have been successfully achieved and the underlying molecular mechanism was elucidated, paving the way for translational application.

Bionanocomposite scaffolds based on chitosan-gelatin and nanodimensional bioactive glass particles: In vitro properties and in vivo bone regeneration.

Bone repair bionanocomposite scaffolds were produced by incorporating dense bioactive glass nanoparticles or mesoporous bioactive glass nanospheres into a chitosan-gelatin polymer blend. The in vitro bioactivity of the scaffolds was assessed in simulated body fluid, and cell viability and osteogenic differentiation assays were performed with dental pulp stem cells. Bone regeneration properties of the scaffold materials were in vivo assessed by using a critical-sized femoral defect model in rat. The scaffold nanocomposites showed excellent cytocompatibility and ability to accelerate the crystallization of bone-like apatite in vitro. Bionanocomposites prepared with bioactive glass nanoparticles were particularly more active to promote the osteogenic differentiation of dental pulp stem cells as judged by the higher activity of alkaline phosphatase. This result is attributed to the faster dissolution of bioactive glass nanoparticles into osteogenic ionic products compared to mesoporous bioactive glass nanospheres. In vivo experiments demonstrated that bioactive glass nanoparticles (5%)/chitosan-gelatin bionanocomposite significantly produces the highest amount of new bone (∼80%) in the defect area after eight weeks of implantation. The bone regeneration capacity exhibited by the scaffolds formulated with nanodimensional bioactive glass particles make them attractive for bone reconstruction applications.

Biodegradable AIEgen-functionalised mesoporous bioactive glass nanoparticles for drug delivery and cell imaging

AIEgen-functionalised mesoporous bioactive glass nanospheres with excellent degradability in an acid environment show potential application in drug delivery and cell imaging.