Highly efficient release of simvastatin from simvastatin-loaded calcium sulphate scaffolds enhances segmental bone regeneration in rabbits.

Highly efficient release of simvastatin from simvastatin-loaded calcium sulphate scaffolds enhances segmental bone regeneration in rabbits.
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从负载辛伐他汀的硫酸钙支架中高效释放辛伐他汀可增强兔的节段骨再生

DOI:
10.3892/mmr.2014.2101
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发表时间:
2014-06
影响因子:
3.4
通讯作者:
Li W
Li W
中科院分区:
医学4区
文献类型:
--
作者:
Huang X;Huang Z;Li W

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许多临床和实验研究调查了辛伐他汀对骨再生的影响。本研究研究了辛伐他汀负载硫酸钙(CS)支架体外释放辛伐他汀的情况,以及CS支架对骨髓间充质干细胞(MSCs)成骨分化的影响,以及CS支架局部应用辛伐他汀对骨再生的影响。采用CS、辛伐他汀负载CS或重组人骨形态发生蛋白2 (rhBMP)-2负载CS处理家兔尺骨,共制备了26个完整的1.2 cm骨缺损。辛伐他汀从载辛伐他汀的CS中高效释放,并保持稳定释放。碱性磷酸酶在与辛伐他汀/CS支架共培养7天和14天的MSCs中高表达。加载rhbmp -2和辛伐他汀的CS组缺损x线分析评分显著高于CS组,组织学检查缺损成骨量显著高于CS组(P<0.05)。rhbmp -2加载组与辛伐他汀加载组在x线评分和骨形成方面无显著差异(P < 0.05)。辛伐他汀能够在体外促进MSCs的成骨分化,当从CS支架局部释放到骨缺损中时,能够刺激骨再生。辛伐他汀的有益作用与rhBMP-2相似。综上所述,本研究提示辛伐他汀负载CS支架在骨组织工程中具有很大的应用潜力。
A number of clinical and experimental studies have investigated the effect of simvastatin on bone regeneration. In the present study, the release of simvastatin from simvastatin-loaded calcium sulphate (CS) scaffolds and the effect of these scaffolds on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs) in vitro and the effect of simvastatin locally applied from CS scaffolds on bone regeneration were investigated. A total of 26 complete 1.2-cm bone defects were created in the ulna of rabbits, which were treated with CS, simvastatin-loaded CS or recombinant human bone morphogenetic protein 2 (rhBMP)-2-loaded CS. Simvastatin was highly efficiently released from simvastatin-loaded CS at the onset and stable release was maintained. Alkaline phosphatase was highly expressed in the MSCs co-cultured with simvastatin/CS scaffolds for 7 and 14 days. The defects treated with rhBMP-2-loaded CS and simvastatin-loaded CS showed significantly higher X-ray analysis scores and a larger amount of bone formation as determined by histology compared with the CS group (P<0.05). No significant differences in the X-ray score and bone formation were observed between groups with rhBMP-2-loaded CS and simvastatin-loaded CS (P>0.05). Simvastatin is capable of promoting osteogenic differentiation of MSCs in vitro and stimulating bone regeneration when locally released from CS scaffolds into bone defects. The beneficial effect of simvastatin was similar to that of rhBMP-2. In conclusion, the present study suggested that the simvastatin-loaded CS scaffolds may have great potential in bone tissue engineering.
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