Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (2): 239-244.doi: 10.3969/j.issn.2095-4344.1511

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Simvastatin sustained-release microspheres promote osteogenesis of bone tissue engineering in vitro

Qing Wei1, Dai Yanjun2, Huang Lijuan1, Ren Jing1, Zheng Jiajun1, Tuo Qiang2, Ren Xiaohua2, Mu Yandong1, 2   

  1. 1School of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China; 2School of Medicine, University of Electronic Science and Technology, Chengdu 610000, Sichuan Province, China
  • Received:2018-10-15 Online:2019-01-18 Published:2019-01-18
  • Contact: Mu Yandong, MD, Chief physician, School of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China; School of Medicine, University of Electronic Science and Technology, Chengdu 610000, Sichuan Province, China
  • About author:Qing Wei, Master candidate, Physician, School of Stomatology, Southwest Medical University, Luzhou 646000, Sichuan Province, China
  • Supported by:

    the Project of Sichuan Science and Technology Department, No. 2016TD0008 (to MYD)

Abstract:

 BACKGROUND: In recent years, domestic and foreign studies have assembled simvastatin sustained-release microspheres onto scaffold materials. It has been found that simvastatin can be used to repair bone defects and good results have been obtained.

OBJECTIVE: To investigate the effect of simvastatin sustained-release microspheres on tissue engineering osteogenesis.
METHODS: Nanoliposome simvastatin sustained-release microspheres were prepared by thin-film dispersion method. The particle size, polydispersity coefficient and encapsulation efficiency were measured. The sustained release properties of free simvastatin solution and simvastatin sustained-release microsphere solution were measured by dialysis device. The third generation of human placental mesenchymal stem cells was inoculated on porous hydroxyapatite ceramic scaffolds. The cells were cultured in two groups after adherent growth. The experimental group was treated with simvastatin sustained-release microspheres, and the normal medium was added to the blank group. Transcriptome sequencing was carried out after 7, 14, 21 days. The expression levels of osteogenic genes were verified by real-time fluorescence quantitative PCR.
RESULTS AND CONCLUSION: (1) The average particle size of simvastatin sustained-release microspheres was (77.27±6.4) nm, the polydispersity coefficient was 0.131±0.040, and the encapsulation efficiency was 85.6%. (2) The rapid release of free simvastatin solution exceeded 80% total dose in the first 3 days. While the simvastatin sustained-release microsphere solution released only about 40% of the drug in the first 3 days, and had been slowly released until the 14th day, and the cumulative release at the 14th day was close to 80%. (3) Transcriptome sequencing showed that the osteogenesis-related genes such as bone morphogenetic protein 2, bone morphogenetic protein 4 and vascular endothelial growth factor were enriched and expressed in the experimental group. (4) Real-time quantitative PCR showed that the mRNA levels of bone morphogenetic protein 2, bone morphogenetic protein 4 and vascular endothelial growth factor were significantly higher in the experimental group than the blank group at 7, 14 and 21 days (P < 0.05). These results indicate that simvastatin sustained-release microspheres can promote osteogenic performance for tissue engineering. 

Key words: Hydroxyapatites, Liposomes, Tissue Engineering

CLC Number: