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Nanotechnology-based approaches are emerging as promising strategies to treat different bone pathologies such as infection, osteoporosis or cancer. To this end, several types of nanoparticles are being investigated, including those based on mesoporous bioactive glasses (MGN) which exhibit exceptional structural and textural properties and whose biological behaviour can be improved by including therapeutic ions in their composition and loading them with biologically active substances. In this study, the bone regeneration capacity and antibacterial properties of MGNs in the SiO 2 –CaO–P 2 O 5 system were evaluated before and after being supplemented with 2.5% or 4% ZnO and loaded with curcumin. in vitro studies with preosteoblastic cells and mesenchymal stem cells allowed determining the biocompatible MGNs concentrations range. Moreover, the bactericidal effect of MGNs with zinc and curcumin against S. aureus was demonstrated, as a significant reduction of bacterial growth was detected in both planktonic and sessile states and the degradation of a pre-formed bacterial biofilm in the presence of the nanoparticles also occurred. Finally, MC3T3-E1 preosteoblastic cells and S. aureus were co-cultured to investigate competitive colonisation between bacteria and cells in the presence of the MGNs. Preferential colonisation and survival of osteoblasts and effective inhibition of both bacterial adhesion and biofilm formation of S. aureus in the co-culture system were detected. Our study demonstrated the synergistic antibacterial effect of zinc ions combined with curcumin and the enhancement of the bone regeneration characteristics of MGNs containing zinc and curcumin to obtain systems capable of simultaneously promoting bone regeneration and controlling infection. In search of a new approach to regenerate bone and fight infections, a nanodevice based on mesoporous SiO 2 –CaO–P 2 O 5 glass nanoparticles enriched with Zn2+ ions and loaded with curcumin was designed. This study demonstrates the synergistic effect of the simultaneous presence of zinc ions and curcumin in the nanoparticles that significantly reduces the bacterial growth in planktonic state and is capable to degrade pre-formed S. aureus biofilms whereas the nanosystem exhibits a cytocompatible behaviour in the presence of preosteoblasts and mesenchymal stem cells. Based on these results, the designed nanocarrier represents a promising alternative for the treatment of acute and chronic infections in bone tissues, while avoiding the significant current problem of bacterial resistance to antibiotics. [Display omitted] [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]

Mesoporous bioactive glass scaffolds (MBG_Scs), based on 80% SiO2–15% CaO–5% P2O5 (in mol.%) mesoporous sol–gel glasses substituted with Ce2O3, Ga2O3 (both 0.2% or 1.0%) and ZnO (0.4% or 2.0%), were synthesized by combination of evaporation-induced self-assembly and rapid prototyping techniques. Cerium, gallium and zinc trace elements were selected because of their inherent beneficial biological properties. Fabricated scaffolds were characterized and compared with unsubstituted scaffold (B_Sc). All of them contained well interconnected ultralarge pores (pores >400μm) ideal for vascular ingrowth and proliferation of cells. Macropores of size 100–400μm were present inside the scaffolds. In addition, low-angle X-ray diffraction showed that B_Sc and scaffolds with substituent contents up to 0.4% exhibited ordered mesoporosity useful for hosting molecules with biological activity. The textural properties of B_Sc were a surface area of 398m2 g−1, a pore diameter of 4.3nm and a pore volume of 0.43cm3 g−1. A slight decrease in surface area and pore volume was observed upon substitution with no distinct effect on pore diameter. In addition, all the MBG_Scs except 2.0% ZnO_Sc showed quite quick in vitro bioactive response. Hence, the present study is a positive addition to ongoing research into preparing bone tissue engineering scaffolds from bioceramics containing elements of therapeutic significance. [ABSTRACT FROM AUTHOR]

Abstract: Parathyroid hormone-related protein (PTHrP) is an important modulator of bone formation. Recently, we reported that PTHrP (107–111) (osteostatin) coating onto mesoporous ceramics confers osteogenic activity to these materials. Bone repair is dramatically compromised in osteopenia/osteoporosis. Thus, we examined the efficacy of unmodified and organically modified SBA15 ceramics loaded with osteostatin in promoting bone repair in an osteoporotic rabbit model. Osteoporosis was induced in New Zealand rabbits by methylprednisolone administration, and healthy rabbits were used as controls. Tested materials were implanted into a femoral cavitary defect, and animals were sacrificed at 2weeks post-implantation. At this time, implants were encapsulated by a variable layer of fibrotic tissue with no evidence of inflammation. Similarly to observations in normal rabbits, both types of osteostatin-loaded bioceramics induced tissue regeneration associated with increased staining for PCNA, Runx2, osteopontin, and/or vascular endothelial growth factor in osteoporotic rabbits. Our present findings demonstrate that these osteostatin-bearing bioceramics increase the early repair response not only in normal bone but also in osteoporotic bone after a local injury. [Copyright &y& Elsevier]

Abstract: Parathyroid hormone-related protein (PTHrP) is an important regulator of bone remodeling. Recent studies show that this protein can induce osteogenic features through its N- and C-terminal domains. Silica-based ordered mesoporous bioceramics with an SBA-15 structure – known to be bioactive and biocompatible – have recently been evaluated for their capacity to uptake and deliver L-tryptophan. This amino acid corresponds to the end position of the 107–111 domain (called osteostatin) of the native C-terminal PTHrP (107–139) fragment, whose true action in bone metabolism is still ill-defined. In the present study, we assessed some effects of the aforementioned biomaterials pressed into disks, loaded or not with osteostatin, in osteoblastic cell cultures. Our data demonstrate that both unmodified and organically modified SBA-15 loaded with this peptide increase cell growth and the expression of several osteoblastic products (alkaline phosphatase, osteocalcin, collagen, osteoprotegerin, receptor activator of nuclear factor-κB ligand and vascular endothelial growth factor) in osteoblastic cells. These findings support the notion that osteostatin coating confers osteogenic features to silica-based ordered mesoporous materials, which make them suitable biomaterials for bone repair. [Copyright &y& Elsevier]

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]

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]

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]