Huang Xin, Huang Zhongming, Li Weixu
Department of Orthopedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
Mol Med Rep. 2014 Jun;9(6):2152-8. doi: 10.3892/mmr.2014.2101. Epub 2014 Apr 1.
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.
多项临床和实验研究探讨了辛伐他汀对骨再生的影响。在本研究中，研究了载辛伐他汀硫酸钙（CS）支架中辛伐他汀的释放情况、这些支架对体外骨髓间充质干细胞（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。在兔尺骨上共制造26个1.2厘米长的完全骨缺损，分别用CS、载辛伐他汀CS或载重组人骨形态发生蛋白2（rhBMP）-2的CS进行治疗。载辛伐他汀CS在开始时能高效释放辛伐他汀，并维持稳定释放。与载辛伐他汀/CS支架共培养7天和14天的MSCs中碱性磷酸酶高表达。与CS组相比，载rhBMP-2的CS和载辛伐他汀的CS治疗的缺损在X线分析评分上显著更高，组织学检查显示骨形成量更大（P<0.05）。载rhBMP-2的CS组和载辛伐他汀的CS组在X线评分和骨形成方面未观察到显著差异（P>0.05）。辛伐他汀能够在体外促进MSCs的成骨分化，并在从CS支架局部释放到骨缺损中时刺激骨再生。辛伐他汀的有益作用与rhBMP-2相似。总之，本研究表明载辛伐他汀的CS支架在骨组织工程中可能具有巨大潜力。
