Strontium and Zinc Co-Doped Mesoporous Bioactive Glass Nanoparticles for Potential Use in Bone Tissue Engineering Applications

Mesoporous bioactive glass nanoparticles (MBGNs) have attracted significant attention as multifunctional nanocarriers for various applications in both hard and soft tissue engineering. In this study, multifunctional strontium (Sr)- and zinc (Zn)-containing MBGNs were successfully synthesized via the microemulsion-assisted sol–gel method combined with a cationic surfactant (cetyltrimethylammonium bromide, CTAB). Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs exhibited spherical shapes in the nanoscale range of 100 ± 20 nm with a mesoporous structure. Sr and Zn were co-substituted in MBGNs (60SiO2-40CaO) to induce osteogenic potential and antibacterial properties without altering their size, morphology, negative surface charge, amorphous nature, mesoporous structure, and pore size. The synthesized MBGNs facilitated bioactivity by promoting the formation of an apatite-like layer on the surface of the particles after immersion in Simulated Body Fluid (SBF). The effect of the particles on the metabolic activity of human mesenchymal stem cells was concentration-dependent. The hMSCs exposed to Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs at 200 μg/mL enhanced calcium deposition and osteogenic differentiation without osteogenic supplements. Moreover, the cellular uptake and internalization of Sr-MBGNs, Zn-MBGNs, and Sr-Zn-MBGNs in hMSCs were observed. These novel particles, which exhibited multiple functionalities, including promoting bone regeneration, delivering therapeutic ions intracellularly, and inhibiting the growth of Staphylococcus aureus and Escherichia coli, are potential nanocarriers for bone regeneration applications.Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation (OPS MHESI)Thailand Science Research and Innovation (TSRI)Thailand Science Research and Innovation (TSRI)Basic Research FundNTUT-KMUTT Joint Research Program, King Mongkut’s University of Technology Thonbur

Assessment of Mechanical/Chemical Properties and Cytotoxicity of Resin-Modified Glass Ionomer Cements Containing Sr/F-Bioactive Glass Nanoparticles and Methacrylate Functionalized Polyacids

This study prepared low-toxicity, elemental-releasing resin-modified glass ionomer cements (RMGICs). The effect of 2-hydroxyethyl methacrylate (HEMA, 0 or 5 wt%) and Sr/F-bioactive glass nanoparticles (Sr/F-BGNPs, 5 or 10 wt%) on chemical/mechanical properties and cytotoxicity were examined. Commercial RMGIC (Vitrebond, VB) and calcium silicate cement (Theracal LC, TC) were used as comparisons. Adding HEMA and increasing Sr/F-BGNPs concentration decreased monomer conversion and enhanced elemental release but without significant effect on cytotoxicity. Rising Sr/F-BGNPs reduced the strength of the materials. The degree of monomer conversion of VB (96%) was much higher than that of the experimental RMGICs (21–51%) and TC (28%). The highest biaxial flexural strength of experimental materials (31 MPa) was significantly lower than VB (46 MPa) (p < 0.01) but higher than TC (24 MPa). The RMGICs with 5 wt% HEMA showed higher cumulative fluoride release (137 ppm) than VB (88 ppm) (p < 0.01). Unlike VB, all experimental RMGICs showed Ca, P, and Sr release. Cell viability in the presence of extracts from experimental RMGICs (89–98%) and TC (93%) was significantly higher than for VB (4%). Experimental RMGICs showed desirable physical/mechanical properties with lower toxicity than the commercial material

Strontium containing bioactive glass nanoparticles

Spherical dense monodispersed bioactive glass nanoparticles (BGNPs) of 90 ± 10 nm in diameter have therapeutic potential due to their ability to be internalised by cellsand to perform the sustained intracellular delivery of therapeutic cations. BGNPs with 25% strontium (Sr) substitution for calcium (Ca) (25%Sr-BGNPs: 90.6 mol% SiO2, 5.0 mol% CaO, and 4.4% mol% SrO) and 75% strontium substitution for calcium (75%Sr-BGNPs: 88.8 mol% SiO2, 1.8 mol% CaO, and 9.4% mol% SrO) were synthesised in the diameter range of 80 – 100 nm through the modified Stӧber process and were physically and biologically characterised. The dense silica nanoparticles (Si-NPs) were fabricated prior to incorporating with calcium nitrate and strontium nitrate as precursor sources of Ca and Sr through calcination at 680 °C. The amount of Ca and Sr incorporated into the silica network of Si-NPs is the key factor for maintaining monodispersity and sustainable release during subsequent degradation in aqueous environments. The incorporation of Ca and Sr were homogenously distributed without affecting the particles’ size, morphology and dispersity. Not all of the nominal Ca and Sr added incorporated into the silica network. Excess Ca and Sr components on the particles’ surface were removed. The in vitro cytotoxicity was evaluated in which cells were in contact with the nanoparticles or their dissolution products. The cell viability of murine pre-osteoblast cell line (MC3T3-E1), human mesenchymal stromal cells (hMSCs), mice murine bone marrow stromal stem cells (BMSCs), and primary macrophages was not affected up to particle concentrations of 250 μg/mL. There was no significant effect on DNA quantity of treated cells with Sr-BGNPs compared to the control (untreated cells). Sr-BGNPs stimulated osteogenic differentiation of MC3T3-E1, hMSCs and BMSCs in the absence of osteogenic supplements, which was confirmed by detecting early-, mid- and late-osteogenic marker expressions and was attributed to their ionic release products. Sr-BGNPs affected both mineralisation and extracellular matrix formation. These particles also showed the potential to reduce osteoclastogenesis, indicated by the reduction in TRAP activity and multinucleated osteoclasts when cultures were supplemented with RANKL.Confocal fluorescent microscopy presented cellular uptake and localisation of the Sr-BGNPs in the cytoplasm of the cells. Transmission electron microscopy (TEM) confirmed internalisation and localisation of Sr-BGNPs inside the endosome/lysosome-like vesicles bordered by a membrane inside the cells via a mixed-uptake mechanism in which the clathrin-dependent endocytosis was the main pathway. In a co-culture system of osteoblasts-osteoclasts, Sr-BGNPs had either the ability to stimulate osteogenic differentiation of MC3T3-E1 in the absence of osteogenic supplements or to inhibit osteoclastogenesis of RAW264.7 in the presence of RANKL and this effect could be attributed to their ionic release products. Sr-BGNPs present great potential for bone regeneration applications. These particles may be used as an alternative injectable or incorporated into nano-composites. To extend the applications of BGNPs, quaternary BGNP systems, in which zinc (Zn) (Sr-ZnBGNPs) or Cerium (Ce) (Sr-CeBGNPs) were incorporated into Sr-BGNPs, were developed through the modified two-step post-functionalisation. Sr-ZnBGNPs had the high capacity to kill cancer cells preferentially compared to normal cells because the released Zn ions that cause toxicity to the cancer cells was more present under an acidic environment. The differences in incorporation between these four cations, including Ca, Sr, Zn, and Ce, might be attributed to the different roles as the network modifier or the network former in the silica network.Open Acces

Assessment of physical/mechanical properties and cytotoxicity of dual-cured resin cements containing Sr-bioactive glass nanoparticles and calcium phosphate

The aim was to develop dual-cured resin cements containing Sr-bioactive glass nanoparticles (Sr-BGNPs; 5 or 10 wt%) and monocalcium phosphate monohydrate (MCPM; 3 or 6 wt%). Effects of additives on degree of monomer conversion (DC), biaxial flexural strength/modulus, shear bond strength (SBS), mass/volume change, color stability, ion release, and cytotoxicity were examined. Controls included material without reactive fillers and Panavia SA Plus (PV). Experimental cements showed higher DC than PV regardless of light activation (p<0.05). Mean SBS and color stability were comparable between experimental cements and PV. Cell viability upon the exposure to sample extracts of experimental cements was 80%-92%. High additive concentrations led to lower strength and modulus than PV (p<0.05). The additives increased mass change, reduced color stability, and promoted ion release. The experimental resin cements demonstrated acceptable mechanical/chemical properties and cytotoxicity. The additives reduced the strength but provided ion release, a desirable action to prevent recurrent caries

Effects of Sr/F-Bioactive Glass Nanoparticles and Calcium Phosphate on Monomer Conversion, Biaxial Flexural Strength, Surface Microhardness, Mass/Volume Changes, and Color Stability of Dual-Cured Dental Composites for Core Build-Up Materials

This study prepared composites for core build-up containing Sr/F bioactive glass nanoparticles (Sr/F-BGNPs) and monocalcium phosphate monohydrate (MCPM) to prevent dental caries. The effect of the additives on the physical/mechanical properties of the materials was examined. Dual-cured resin composites were prepared using dimethacrylate monomers with added Sr/F-BGNPs (5 or 10 wt%) and MCPM (3 or 6 wt%). The additives reduced the light-activated monomer conversion by ~10%, but their effect on the conversion upon self-curing was negligible. The conversions of light-curing or self-curing polymerization of the experimental materials were greater than that of the commercial material. The additives reduced biaxial flexural strength (191 to 155 MPa), modulus (4.4 to 3.3), and surface microhardness (53 to 45 VHN). These values were comparable to that of the commercial material or within the acceptable range of the standard. The changes in the experimental composites&rsquo; mass and volume (~1%) were similar to that of the commercial comparison. The color change of the commercial material (1.0) was lower than that of the experimental composites (1.5&ndash;5.8). The addition of Sr/F-BGNPs and MCPM negatively affected the physical/mechanical properties of the composites, but the results were satisfactory except for color stability

An in vitro assessment of biaxial flexural strength, degree of monomer conversion, color stability, and ion release in provisional restorations containing Sr-bioactive glass nanoparticles

AbstractThis study examined the mechanical and chemical properties of an experimental provisional restoration containing Sr-bioactive glass nanoparticles (Sr-BGNPs) compared to commercial provisional materials. The experimental material (TempS10) contained dimethacrylate monomers with added 10 wt% Sr-BGNPs. The degree of monomer conversion (DC) of self-curing (n = 5), biaxial flexural strength (BFS)/modulus (BFM) (n = 5), and color changes (ΔE*00) of materials in red wine (n = 5) were determined. Additionally, ion release (Ca, P, and Sr) in water at 2 weeks was examined (n = 3). The commercial materials tested included polymethyl methacrylate-based provisional material (Unifast) and bis-acrylic materials (Protemp4 and Cooltemp). TempS10 exhibited a comparable degree of monomer conversion (49%) to that of Protemp4 (60%) and Cooltemp (54%) (p > 0.05). The DC of Unifast (81%) was significantly higher than that of other materials (p < 0.05). TempS10 showed a BFS (126 MPa) similar to Cooltemp (102 MPa) and Unifast (123 MPa), but lower than Protemp4 (194 MPa). The immersion time for 2 weeks exhibited no detrimental effect on the strength and modulus of all materials. The highest ΔE*00 at 24 h and 2 weeks was observed with TempS10, followed by Cooltemp, Unifast, and Protemp4. Only TempS10 showed a detectable amount of Ca (0.69 ppm), P (0.12 ppm), and Sr (3.01 ppm). The experimental provisional resin restoration containing Sr-BGNPs demonstrated polymerization and strength comparable to those of bis-acryl provisional restorations but with the added benefit of ion-releasing properties. However, the experimental material demonstrated unsatisfactory color stability

Assessment of Physical/Mechanical Performance of Dental Resin Sealants Containing Sr-Bioactive Glass Nanoparticles and Calcium Phosphate

The aim of this study was to assess the chemical/mechanical properties of ion-releasing dental sealants containing strontium-bioactive glass nanoparticles (Sr-BGNPs) and monocalcium phosphate monohydrate (MCPM). Two experimental sealants, TS1 (10 wt% Sr-BGNPs and 2 wt% MCPM) and TS2 (5 wt% Sr-BGNPs and 4 wt% MCPM), were prepared. Commercial controls were ClinproXT (CP) and BeautiSealant (BT). The monomer conversion (DC) was tested using ATR&ndash;FTIR (n = 5). The biaxial flexural strength (BFS) and modulus (BFM) were determined (n = 5) following 24 h and 7 days of immersion in water. The Vickers surface microhardness (SH) after 1 day in acetic acid (conc) versus water was tested (n = 5). The bulk and surface calcium phosphate precipitation in simulated body fluid was examined under SEM-EDX. The ion release at 4 weeks was analyzed using ICP-MS (n = 5). The DC after 40 s of light exposure of TS1 (43%) and TS2 (46%) was significantly lower than that of CP (58%) and BT (61%) (p &lt; 0.05). The average BFS of TS1 (103 MPa), TS2 (123 MPa), and BT (94 MPa) were lower than that of CP (173 MPa). The average BFM and SH of TS1 (2.2 GPa, 19 VHN) and TS2 (2.0 GPa, 16 VHN) were higher than that of CP (1.6 GPa, 11 VHN) and BT (1.3 GPa, 12 VHN). TS1 showed higher Ca, P, and Sr release than TS2. Bulk calcium phosphate precipitation was detected on TS1 and TS2 suggesting some ion exchange. In conclusion, the DC of experimental sealants was lower than that of commercial materials, but their mechanical properties were within the acceptable ranges. The released ions may support remineralizing actions

The development of resin-coating materials for enhancing elemental release of coated glass ionomer cements

This study aimed to develop resin coatings containing monocalcium phosphate monohydrate (MCPM), Sr/F-doped bioactive glass (Sr/F-BAGs), and pre-reacted glass ionomer fillers (SPG) that enhance ion release without detrimentally affecting the mechanical properties of GIC. The objective of this study was to evaluate the degree of monomer conversion (DC), biaxial flexural strength, surface microhardness, and ion release of the GICs coated with experimental coating materials compared to a commercial product (EQUIA Coat, EC). Four experimental resin coating materials containing 10–20 wt% of MCPM with Sr/F-BAGs and 5–10 wt% SPG were prepared. The DC of the coating material was determined using ATR-FTIR. The flexural strength and surface microhardness of the coated GICs were assessed. Fluoride and elemental (Ca,P,Sr,Si,Al) release were measured using fluoride-specific electrodes and ICP-OES. The DC of the experimental coating material (60–69 %) was higher than that of EC (55 %). The strength of GICs coated with experimental materials (35–40 MPa) was comparable to EC (37 MPa). However, their surface microhardness (13–24 VHN) was lower than EC (44 VHN). The experimental coating materials reduced fluoride release by ∼43 %, similar to EC (∼40 %). However, experimental coating materials promoted higher P and Sr release than EC. In conclusion, GICs coated with the experimental resin coating containing ion-releasing additives exhibited mechanical properties similar to those of the commercial product. The new coating materials promoted a higher level of ion release for GICs. These properties could potentially enhance remineralizing actions for the coated GICs