Simvastatin-loaded porous implant surfaces stimulate preosteoblasts differentiation: an in vitro study.
OBJECTIVE
Recent studies demonstrate that simvastatin stimulates bone formation, suggesting the potential application in dental implantology. In this study, our lab developed a simvastatin-loaded titanium porous surface. The aim was to investigate the effect of simvastatin-loaded titanium surfaces on the promotion of osteogenesis in preosteoblasts (MC3T3-E1) in vitro.


METHODS
The control group consisted of cells cultured on titanium disks without any intervention for different time intervals (4, 7, and 14 days), and the experimental groups (simvastatin-loaded groups) consisted of cells cultured on titanium disks that were preincubated in varying concentration (10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L, and 10(-4) mol/L) of simvastatin for the same time intervals of the control group. Alkaline phosphatase (ALP) activity, type I collagen synthesis, and osteocalcin release were used to measure the cellular osteoblastic activities.


RESULTS
All simvastatin-loaded groups showed increased ALP activity compared with the control group at every time point, especially the 10(-7) mol/L group, which significantly increased the activity almost fourfold at 4 days (P < .05). In the type I collagen synthesis assay, all simvastatin-loaded groups showed an increase, and the effect was inverse dose dependent (maximal at 10(-7) mol/L). This stimulatory effect of simvastatin was also observed in the osteocalcin release assay (P < .05; at 10(-7) mol/L, 10(-6) mol/L, maximal at 10(-7) mol/L).


CONCLUSIONS
These results indicate that simvastatin-loaded porous implant surfaces promote accelerated osteogenic differentiation of preosteoblasts, which have the potential to improve the nature of osseointegration.
Yang
Fan
F
Department of Oral Implantology, Stomatology Hosptital, Medical School, Zhejiang University, Hangzhou, China.
Zhao
Shi-fang
SF
Zhang
Feng
F
He
Fu-ming
FM
Yang
Guo-li
GL
D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000096:biosynthesis; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D016348:Osseointegration / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000096:biosynthesis; D016062:Porosity; D019821:Simvastatin / Q000494:pharmacology*; D013499:Surface Properties; D014025:Titanium
D024042:Collagen Type I; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015675:Osteocalcin; D019821:Simvastatin; D014025:Titanium; D000469:Alkaline Phosphatase