In vitro and in vivo evaluation of the osteogenic ability of implant surfaces with a local delivery of simvastatin.
OBJECTIVE
This study established local delivery with a calcium phosphate (CaP) coating and investigated effects of delivery on implant osseointegration by in vitro and in vivo experiments.


METHODS
Simvastatin was prepared onto titanium surfaces with varying concentration (10⁻⁷, 10⁻⁶, 10⁻⁵, and 10⁻⁴ mol/L). Surface characteristics were performed by field-emission scanning electron microscope (FSEM), x-ray diffractometer (XRD), and fourier transform infrared spectroscopy (FTIR). Alkaline phosphatase activity (ALP) and osteocalcin release were used to measure osteoblastic activities. Ovariectomized rats randomly received control and test implants in both tibiae. After 4 and 12 weeks of implantation, the tibiae were retrieved and prepared for histomorphometric evaluation.


RESULTS
FSEM observation showed that the size of flakes decreased with an increase of simvastatin concentrations. XRD and FTIR examinations demonstrated that all coatings were composed of octacalcium phosphate (OCP). Simvastatin-loaded titanium surface had an increased effect on ALP activities at different concentrations on day 4 and day 7, and only the 10⁻⁶ mol/L group showed significant differences on day 14 (P<.05). The 10⁻⁶ mol/L group showed significant expression of osteocalcin (P<.05). Test implants (10⁻⁶ mol/L) showed a significantly greater bone area and bone-implant contact compared to control implants during the observation periods (P<.05).


CONCLUSIONS
It was concluded that the local delivery of simvastatin was established onto implant surfaces using the biomimetic CaP coating and could improve osteoblast function and implant osseointegration in ovariectomized rats.
Shifang
S
Zhao
Fang
F
Wen
Fuming
F
He
Li
L
Liu
Guoli
G
Yang
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D040761:Biomimetic Materials / Q000008:administration & dosage; D002130:Calcium Phosphates / Q000378:metabolism; D020099:Coated Materials, Biocompatible; D016503:Drug Delivery Systems / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D020007:Implants, Experimental; D016348:Osseointegration / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism; D010052:Ovariectomy; D019919:Prosthesis Implantation / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013499:Surface Properties; D013977:Tibia / Q000187:drug effects / Q000601:surgery*; D013997:Time Factors; D014025:Titanium / Q000737:chemistry
D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D015675:Osteocalcin; C022045:octacalcium phosphate; C020243:calcium phosphate; D019821:Simvastatin; D014025:Titanium; D000469:Alkaline Phosphatase