| 1. |
- Cecchinato, Francesca, et al.
(författare)
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In vitro evaluation of human fetal osteoblast response to magnesium loaded mesoporous TiO2 coating.
- 2014
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 102:11, s. 3862-3871
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Tidskriftsartikel (refereegranskat)abstract
- This work aimed to evaluate the in vitro response of Transfected Human Foetal Osteoblast (hFOB) cultured on a magnesium-loaded mesoporous TiO2 coating. The application of mesoporous films on titanium implant surfaces has shown very promising potential to enhance osseointegration. This type of coating has the ability to act as a framework to sustain bioactive agents and different drugs. Magnesium is the element that, after calcium, is the most frequently used to dope titanium implant surfaces, since it is crucial for protein formation, growth factor expression, and aids for bone mineral deposition on implant surfaces. Mesoporous TiO2 films with an average pore-size of 6 nm were produced by the evaporation-induced self-assembly method (EISA) and deposited onto titanium discs. Magnesium loading was performed by soaking the mesoporous TiO2 discs in a magnesium chloride solution. Surface characterization was conducted by SEM, XPS, optical interferometry, and AFM. Magnesium release profile was assessed at different time points using a Magnesium Detection kit. Cell morphology and spreading were observed with SEM. The cytoskeletal organization was stained with TRITC-conjugated Phalloidin and cell viability was evaluated through a mitochondrial colorimetric (MTT) assay. Furthermore, gene expression of bone markers and cell mineralization were analyzed by real time RT-PCR and alizarin-red staining, respectively. The surface chemical analysis by XPS revealed the successful adsorption of magnesium to the mesoporous coating. The AFM measurements revealed the presence of a nanostructured surface roughness. Osteoblasts viability and adhesion as well as the gene expression were unaffected by the addition of magnesium possibly due to its rapid burst release, however, were enhanced by the 3D nanostructure of the TiO2 layer.
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| 2. |
- Cecchinato, Francesca, et al.
(författare)
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Osteogenic potential of human adipose-derived stromal cells on 3-dimensional mesoporous TiO2 coating with magnesium impregnation
- 2015
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Ingår i: Materials Science and Engineering C. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 52, s. 225-234
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the osteogenic response of human adipose-derived stromal cells (ADScs) to mesoporous titania (TiO2) coatings produced with evaporation-induced self-assembly method (EISA) and loaded with magnesium. Our emphasis with the magnesium release functionality was to modulate progenitor cell osteogenic differentiation under standard culture conditions. Osteogenic properties of the coatings were assessed for stromal cells by means of scanning electron microscopy (SEM) imaging, colorimetric mitochondrial viability assay (MTT), colorimetric alkaline phosphates activity (ALP) assay and real time RT-polymerase chain reaction (PCR). Using atomic force microscopy (AFM) it was shown that the surface expansion area (S-dr) was strongly enhanced by the presence of magnesium. From MTT results it was shown that ADSc viability was significantly increased on mesoporous surfaces compared to the non-porous one at a longer cell culture time. However, no differences were observed between the magnesium impregnated and non-impregnated surfaces. The alkaline phosphatase activity confirmed that ADSc started to differentiate into the osteogenic phenotype after 2 weeks of culturing. The gene expression profile at 2 weeks of cell growth showed that such coatings were capable to incorporate specific osteogenic markers inside their interconnected nano-pores and, at 3 weeks, ADSc differentiated into osteoblasts. Interestingly, magnesium significantly promoted the osteopontin gene expression, which is an essential gene for the early biomaterial-cell osteogenic interaction. (C) 2015 Elsevier B.V. All rights reserved.
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| 3. |
- Galli, Silvia, et al.
(författare)
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Local release of magnesium from mesoporous TiO2 coatings stimulates the peri-implant expression of osteogenic markers and improves osteoconductivity in vivo
- 2014
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Ingår i: Acta Biomaterialia. - : Elsevier. - 1742-7061 .- 1878-7568. ; 10:12, s. 5193-5201
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Tidskriftsartikel (refereegranskat)abstract
- Local release of Mg ions from titanium implant surfaces has been shown to enhance implant retention and integration. To clarify the biological events that lead to this positive outcome, threaded implants coated with mesoporous TiO2 thin films were loaded with Mg-ions and placed in the tibia of rabbits for 3 weeks, after surface characterization. Non-loaded mesoporous coated implants were used as controls. Peri-implant gene expression of a set of osteogenic and inflammatory assays was quantified by means of real-time quantitative polymerase chain reaction. The expression of three osteogenic markers (OC, RUNX-2 and IGF-1) was significantly more pronounced in the test specimens, suggesting that the release of Mg ions directly at the implant sites may stimulate an osteogenic environment. Furthermore, bone healing around implants was evaluated on histological slides and by diffraction-enhanced imaging (DEI), using synchrotron radiation. The histological analysis demonstrated new bone formation around all implants, without negative responses, with a significant increase in the number of threads filled with new bone for test surfaces. DEI analysis attested the high mineral content of the newly formed bone. Improved surface osteoconductivity and increased expression of genes involved in the bone regeneration were found for magnesium-incorporation of mesoporous TiO2 coatings.
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| 4. |
- Galli, Silvia, et al.
(författare)
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Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone
- 2017
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Ingår i: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4981 .- 1552-4973. ; 105:7, s. 2118-2125
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe release of magnesium ions (Mg2+) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing. Methods: Titanium implants were coated with mesoporous titania layers and either loaded with Mg2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. Results: Mg2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. Significance: The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation.
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| 5. |
- Galli, Silvia, et al.
(författare)
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Osteoconductive potential of mesoporous titania implant surfaces loaded with magnesium : an experimental study in the rabbit
- 2015
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Ingår i: Clinical Implant Dentistry and Related Research. - : John Wiley & Sons. - 1523-0899 .- 1708-8208. ; 17:6, s. 1048-1059
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mesoporous coatings enable incorporation of functional substances and sustainedly release them at the implant site. One bioactive substance that can be incorporated in mesoporous is magnesium, which is strongly involved in bone metabolism and in osteoblast interaction. Purpose: The aim of this experimental study was to evaluate the effect of incorporation of magnesium into mesoporous coatings of oral implants on early stages of osseointegration. Material and Methods: Titanium implants were coated with thin films of mesoporous TiO2 having pore diameters of 6 nm and were loaded with magnesium. The implant surfaces were extensively characterized by means of interferometry, atomic force microscopy, scanning electron microscopy, and energy-dispersive spectroscopy and then placed in the tibiae of 10 rabbits. After 3 weeks of healing, osseointegration was evaluated by means of removal torque testing and histology and histomorphometry. Results: Histological and biomechanical analyses revealed no side effects and successful osseointegration of the implants. The biomechanical evaluation evidenced a significant effect of magnesium doping on strengthening the implant-bone interface. Conclusions: A local release of magnesium from the implant surfaces enhances implant retention at the early stage of healing (3 weeks after implantation), which is highly desirable for early loading of the implant.
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| 6. |
- Galli, Silvia, et al.
(författare)
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The effect of magnesium on early osseointegration in osteoporotic bone : a histological and gene expression investigation
- 2017
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 28:7, s. 2195-2205
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Tidskriftsartikel (refereegranskat)abstract
- Magnesium has a key role in osteoporosis and could enhance implant osseointegration in osteoporotic patients. Titanium implants impregnated with Mg ions were installed in the tibia of ovariectomized rats. The release of Mg induced a significant increase of bone formation and the expression of anabolic markers in the peri-implant bone. The success of endosseous implants is highly predictable in patients possessing normal bone status, but it may be impaired in patients with osteoporosis. Thus, the application of strategies that adjuvate implant healing in compromized sites is of great interest. Magnesium has a key role in osteoporosis prevention and it is an interesting candidate for this purpose. In this study, the cellular and molecular effects of magnesium release from implants were investigated at the early healing stages of implant integration. Osteoporosis was induced in 24 female rats by means of ovariectomy and low-calcium diet. Titanium mini-screws were coated with mesoporous titania films and were loaded with magnesium (test group) or left as native (control group). The implants were inserted in the tibia and femur of the rats. One, 2 and 7 days after implantation, the implants were retrieved and histologically examined. In addition, expression of genes was evaluated in the peri-implant bone tissue at day 7 by means of quantitative polymerase chain reactions with pathway-oriented arrays. The histological evaluation revealed that new bone formation started already during the first week of healing for both groups. However, around the test implants, new bone was significantly more abundant and spread along a larger surface of the implants. In addition, the release of magnesium induced a significantly higher expression of BMP6. These results provide evidence that the release of magnesium promoted rapid bone formation and the activation of osteogenic signals in the vicinity of implants placed in osteoporotic bone.
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| 7. |
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| 8. |
- Karlsson, Johan, 1984, et al.
(författare)
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In vivo biomechanical stability of osseointegrating mesoporous TiO2 implants
- 2012
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 8:12, s. 4438-4446
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Tidskriftsartikel (refereegranskat)abstract
- Mesoporous materials are of high interest as implant coatings to receive an enhanced osseointegration. In this study, titanium implants coated with mesoporous TiO(2) thin films have been evaluated both in vitro and in vivo. Material characterization showed that, with partly crystalline TiO(2) (anatase), long-range-ordered hydrophilic mesoporous thin films with a pore size of 6nm were obtained. Evaluation of the mechanical resistance showed that the films were robust enough to withstand the standard implantation procedure. In vitro apatite formation was studied using simulated body fluids, showing that the pores are accessible for ions and that formation of apatite was increased due to the presence of the mesopores. An in vivo study using a rabbit model was executed in which the removal torque and histomorphometry were evaluated. The results show that the biomechanical stability of the TiO(2) coating was unaffected by the presence of mesopores and that osseointegration was achieved without any signs of inflammation.
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| 9. |
- Karlsson, Johan, 1984, et al.
(författare)
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Localized controlled drug delivery from mesoporous implants
- 2014
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Ingår i: Technical Proceedings of the 2014 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2014. Washington, DC, United States, 15-18 June 2014. - 9781482258271
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Konferensbidrag (refereegranskat)abstract
- Mesoporous materials possess both a well-defined topography on the nanometer scale, and they may serve as hosts for drugs. In this work, titanium implants coated with mesoporous TiO2 thin films have been evaluated both in vitro and in vivo. Material characterization showed that, long-range ordered mesoporous TiO2, with a pore-size of 6 nm, and a narrow pore-size distribution were obtained. An in vivo study demonstrated that the films were robust enough to withstand the implantation procedure. The in vitro apatite formation experiments showed that formation of apatite was higher on the mesoporous surface compared to its nonporous counterpart. In a separate in vivo study, two osteoporosis drugs, alendronate (ALN) and raloxifene (RLX), were immobilised into the nanoporous oxide films. The in vitro drug release tests carried out showed a sustained release of both drugs. The osteogenic response after 28 days of implantation of the drug-loaded implants showed a significantly improved bone fixation.
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| 10. |
- Raphel, J., et al.
(författare)
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Engineered protein coatings to improve the osseointegration of dental and orthopaedic implants
- 2016
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 83, s. 269-282
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Tidskriftsartikel (refereegranskat)abstract
- Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cpTi and Ti6A14V surfaces using scalable spin and dip coating processes with photoactive covalent cross linking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 h, compared to 38% adhesion on uncoated Ti6A14V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6A14V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell -adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure.
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