Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat
Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat
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DOI：
10.1111/clr.13105
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发表时间：
2018-02-01
影响因子：
4.3
通讯作者：
Lang, Niklaus P.
中科院分区：
文献类型：
--
作者：
Hao, Jia;Chou, Joshua;Lang, Niklaus P.
目的：探讨新型原位凝胶形成系统--SrHA/Alg(锶羟基磷灰石/海藻酸盐)骨膜下注射对大鼠颅骨垂直向骨增厚的影响。材料与方法将合成的SrHA/Alg溶液与不同剂量的SIM(0.01、0.02、0.1、0.2 mg)复合，形成以下几组：(1)单纯的SrHA/Alg，(2)SrHA/Alg/0.01，(3)SrHA/Alg/0.02，(4)SrHA/Alg/0.1，(5)SrHA/Alg/0.2。分析SIM的释放模式，并观察大鼠原代骨膜来源细胞(PDC)的反应。20只雄性Wistar大鼠进行颅骨骨膜下注射实验，每只大鼠接受200-L单次骨膜下注射含不同剂量SIM(0、0.01、0.02和0.1 mg)的SrHA/Alg(n=5)。0.2 mg剂量组没有进行体内试验，因为在体外发现了严重的毒性。结果SrHA/Alg/0.2组SIM释放缓慢，PDC活性下降。在SrHA/Alg/0.01和SrHA/Alg/0.02组中，碱性磷酸酶阳性面积和矿化面积显著增加(p
ObjectivesTo evaluate whether the subperiosteal injection of simvastatin (SIM) with a novel in situ gel-forming system, SrHA/Alg (strontium hydroxyapatite/alginate), can stimulate vertical bone augmentation in a rat calvarial model.Material and methodsThe SrHA/Alg solution was synthesized and combined with different doses of SIM (0.01, 0.02, 0.1, and 0.2mg) to form the following groups: (1) SrHA/Alg only, (2) SrHA/Alg/0.01, (3) SrHA/Alg/0.02, (4) SrHA/Alg/0.1, and (5) SrHA/Alg/0.2. The SIM release pattern was analyzed, and rat primary periosteum-derived cell (PDC) responses were investigated. Twenty male Wistar rats were enrolled in the calvarial subperiosteal injection experiment with each animal receiving a 200-l single subperiosteal injection of SrHA/Alg with different amounts of SIM (0, 0.01, 0.02, and 0.1mg) incorporated (n=5). The 0.2mg dose group was not tested in vivo due to the severe toxicity found in vitro. The new bone formation was assessed histologically and radiologically at 8weeks.ResultsThe slow release of SIM was confirmed, and PDC viability decreased in the SrHA/Alg/0.2 group. Alkaline phosphatase positive areas and mineralization areas were significantly greater in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups (p