Objectives. The present study intended to further verify that simvastatin-loaded nanomicelles (SVNs) enhanced the role of simvastatin (SV) in promoting osteoblast differentiation in vitro and to evaluate the effect of SVNs on bone defect repair in vivo. Methods. SVNs were synthesized by dialysis. MG63 cells were subjected to intervention with 0.25 μmol/l of SVNs and SV. A 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay kit and flow cytometry were used to determine cell proliferation activity, cell cycle distribution, and apoptosis. The osteoblastic differentiation of MG 63 cells was evaluated by measuring alkaline phosphatase (ALP) activity, ALP staining, and the expression levels of the osterix (Osx) and osteocalcin (OC) proteins. In addition, 0.5 mg of SVNs or SV was applied to the skull defect area of rabbits. Micro-CT, hematoxylin and eosin (HE) staining, and Masson’s trichrome staining were used for qualitative and quantitative evaluation of new bone in three dimensions and two dimensions. Results. The SVNs had a mean diameter of 38.97 nm. The encapsulation and drug-loading efficiencies were and , respectively. In vitro, SVNs and SV can inhibit the proliferation activity and promote osteogenic differentiation of MG63 cells by arresting MG63 cells at the G0/G1 phase without increasing the apoptosis rate. In vivo quantitative results showed that the bone mineral density (BMD), bone volume (BV)/total volume (TV) ratio, and trabecular number (Tb.N) in the gelatin sponge with SVNs (SVNs-GS) group and gelatin sponge with SV (SV-GS) group were 362.1%, 292.0%; 181.3%, 158.0%; and 215.2%, 181.8% of those in the blank control (BC) group, respectively. Histological results identified the new bone tissue in each group as irregular fibrous bone, and the arrangement of trabecular bone was disordered. There were significantly more osteoblasts and new capillaries around the trabecular bone in the SVNs-GS group and SV-GS group than in both the BC and drug-free nanomicelle (DFNs) groups. Both in vitro and in vivo, SVNs exhibited greater osteogenic efficacy than SV. Conclusion. SVNs significantly improved the osteogenic efficacy of SV.

中文翻译：

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载有辛伐他汀的Nanomicelles增强辛伐他汀的成骨作用

目标。本研究旨在进一步验证载有辛伐他汀的纳米胶束（SVN）增强了辛伐他汀（SV）在体外促进成骨细胞分化中的作用，并评估SVN对体内骨缺损修复的作用。方法。通过透析合成SVN。MG63细胞进行干预0.25  μ摩尔/升的SVN和SV。使用3-（4,5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑（MTS）分析试剂盒和流式细胞仪确定细胞增殖活性，细胞周期分布和凋亡。通过测量碱性磷酸酶（ALP）活性，ALP染色以及osterix（Osx）和骨钙素（OC）蛋白的表达水平来评估MG 63细胞的成骨分化。另外，将0.5mg SVN或SV施用于兔子的颅骨缺损区域。使用Micro-CT，苏木精和曙红（HE）染色以及Masson三色染色在三个维度和两个维度对新骨进行定性和定量评估。结果。SVN的平均直径为38.97 nm。封装和载药效率分别为 和 ，分别。在体外，SVN和SV可通过将MG63细胞阻滞在G0 / G1期而抑制其增殖活性并促进MG63细胞的成骨分化，而不增加细胞凋亡率。体内定量结果显示，SVNs（SVNs-GS）组和明胶海绵的明胶海绵中的骨矿物质密度（BMD），骨体积（BV）/总体积（TV）比和骨小梁数（Tb.N） SV（SV-GS）组分别为362.1％，292.0％; 181.3％，158.0％；分别为空白对照组（BC）组的215.2％和181.8％。组织学结果表明，每组中的新骨组织为不规则的纤维骨，并且小梁骨的排列混乱。SVNs-GS组和SV-GS组的骨小梁周围成骨细胞和新的毛细血管明显多于BC组和无药纳米胶束（DFNs）组。在体外和体内，SVN都比SV表现出更大的成骨功效。结论。SVN显着改善了SV的成骨功效。