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- Harmankaya, Necati, 1983, et al.
(author)
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Raloxifene and alendronate containing thin mesoporous titanium oxide films improve implant fixation to bone.
- 2013
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In: Acta biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 9:6, s. 7064-73
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Journal article (peer-reviewed)abstract
- This study tested the hypothesis that osteoporosis drug-loaded mesoporous TiO2 implant coatings can be used to improve bone-implant integration. Two osteoporosis drugs, Alendronate (ALN) and Raloxifene (RLX), were immobilized in nanoporous oxide films prepared on Ti screws and evaluated in vivo in rat tibia. The drug release kinetics were monitored in vitro by quartz crystal microbalance with dissipation and showed sustained release of both drugs. The osteogenic response after 28days of implantation was evaluated by quantitative polymerase chain reaction (qPCR), removal torque, histomorphometry and ultrastructural interface analysis. The drug-loaded implants showed significantly improved bone fixation. In the case of RLX, stronger bone-remodelling activity was observed compared with controls and ALN-loaded implants. The ultrastructural interface analysis revealed enhanced apatite formation inside the RLX coating and increased bone density outside the ALN coating. Thus, this novel combination of a thin mesoporous TiO2 carrier matrix and appropriate drugs can be used to accelerate implant fixation in trabecular bone.
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- Karlsson, Johan, 1984, et al.
(author)
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Ex vivo alendronate localization at the mesoporous titania implant/bone interface
- 2015
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In: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 26
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Journal article (peer-reviewed)abstract
- An attractive approach in implant technology is local drug delivery, and design of efficient, safe and reliable treatments. Ourhitherto strategy has been to coat Ti implants with a thin mesoporous TiO2 film that in turnis loaded with an osteoporosis drug, such as Alendronate (ALN) that is known to suppress osteoclastic activity. This system has proven highly successful and results in excellent osseointegration. However, more detailed information about drug-release and distribution at the bone/implant interface is needed. In this study, (14)C-ALN loaded titanium implants were placed up to 8weeks into rat tibia and the spatial-temporal distribution of the drug was evaluated. Autoradiography data demonstrated a sustained release of (14)C-ALN and the releaseddrug remained bound to bone in close vicinity, within 500 micrometers,of the implants. Liquid scintillation counting experiments confirmed that the distal transport of released (14)C-ALN was extremely low. The results are favorable as they show that ALN stays for a long time in the vicinity of the implant and may therefore improve for a long time the mechanical fixation of bone anchored implants. Moreover, these findings suggest due to the low systemic spreading a minimal risk of Alendronate related systemic side effects.
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| 4. |
- Karlsson, Johan, 1984, et al.
(author)
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Localized controlled drug delivery from mesoporous implants
- 2014
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In: 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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Conference paper (peer-reviewed)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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| 5. |
- Karlsson, Johan, 1984, et al.
(author)
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Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants
- 2016
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In: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 104:10, s. 2466-2475
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Journal article (peer-reviewed)abstract
- Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1a/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1a from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1a were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments.
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