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      The possibility of healing alveolar bone defects with simvastatin thermosensitive gel: in vitro/in vivo evaluation

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          In this study, simvastatin (SVT) in situ gels were successfully produced by our group.


          The preparations were characterized in the following aspects: in vitro gelation, drug release, stability and pharmacodynamics.


          In this study, drug content of prepared gels was found to be in the range between 89 and 92%. The pH value was in the range between 6.5 and 7.0. The gelation temperature of the prepared thermogelling solutions was 37°C. In vitro release showed that the release of SVT from in situ gels was slow with burst effects at an early stage. Researches indicated that intraorally slow release SVT in situ gels could effectively promote bone regeneration repair of alveolar bone defect.


          This drug delivery system could prove to be a novel form able to prolong the residence time and to control the release of drug when administered into the oral cavity.

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          Most cited references 18

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          Biodegradability and biocompatibility of thermoreversible hydrogels formed from mixing a sol and a precipitate of block copolymers in water.

          This study examines in vitro and in vivo biodegradation and biocompatibility of a thermogelling polymeric material, which we call a mixture hydrogel. The mixture contains two ABA-type triblock copolymers poly(d,l-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) with different block ratios, and one polymer is soluble in water, but the other is not. The aqueous solutions of some mixtures with appropriate mix ratios form hydrogels at the body temperature. The degradation of mixture hydrogels proceeded by hydrolysis of ester bonds followed by the erosion of gel in phosphate saline buffer solution at 37 degrees C for nearly one month. The mass loss and reduction of molecular weight were detected. The mix ratio was found to significantly influence the degradation profiles. The rapid in vivo gel formation was confirmed after subcutaneous injection of the thermogelling copolymer mixtures into Sprague-Dawley rats. The in vivo degradation was a bit accelerated than in vitro hydrolysis, and the persistence time of injected hydrogels in vivo was found to be tuned by mix ratio. MTT assay and histological observations were used to examine the copolymer mixtures. Both in vitro and in vivo results illustrate acceptable biocompatibility of our materials. As such, the thermosensitive hydrogel of copolymer mixture is confirmed to be a promising candidate of an injectable biomaterial for drug delivery and tissue engineering.
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            The effect of simvastatin on chemotactic capability of SDF-1α and the promotion of bone regeneration.

            The purpose of this study was to investigate the cooperative effects of simvastatin (SIM) and stromal cell-derived factor-1α (SDF-1α) on the osteogenic and migration capabilities of mesenchymal stem cells (MSCs), and construct a cell-free bone tissue engineering system comprising SIM, SDF-1α and scaffold. We found that 0.2 μm SIM significantly increased alkaline phosphatase activity (P < 0.05) of mouse bone marrow MSCs with no inhibition of cell proliferation, and enhanced the chemotactic capability of SDF-1α (P < 0.05). Next, we constructed a novel cell-free bone tissue engineering system using PLGA loaded with SIM and SDF-1α, and applied it in critical-sized calvarial defects in mice. New bone formation in the defect was evaluated by micro-CT, HE staining and immunohistochemistry. The results showed that PLGA loaded with SIM and SDF-1α promoted bone regeneration significantly more than controls. We investigated possible mechanisms, and showed that SDF-1α combined with SIM increased MSC migration and homing in vivo, promoted angiogenesis and enhanced the expression of BMP-2 in newly-formed bone tissue. In conclusion, SIM enhanced the chemotactic capability of SDF-1α and the cell-free bone tissue engineering system composed of SIM, SDF-1α and scaffold promoted bone regeneration in mouse critical-sized calvarial defects.
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              Protective mechanisms of simvastatin in experimental periodontal disease.

              Simvastatin is a cholesterol-lowering drug whose pleiotropic effects may have a therapeutic impact on bone. This study evaluates the effect of simvastatin on rats subjected to experimental periodontal disease.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                04 July 2018
                : 12
                : 1997-2003
                Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, China, yuyouchengdr@ 12345621cn.com
                Author notes
                Correspondence: Youcheng Yu, Department of Stomatology, Zhongshan Hospital, Fudan University, 180# Fenlin Road, Xuhui District, Shanghai, China, Tel +86 21 6404 1990, Email yuyouchengdr@ 12345621cn.com
                © 2018 Ruan et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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