Cholesterol production inhibitor (statin) increased angiogenesis in surgically created femoral defect in an animal model.

Abstract

This study investigated the effects of dual delivery of statin and vancomycin on the healing process of a femoral defect injury using tricalcium phosphate lysine (TCPL) delivery system in an animal model. The experimental design consisted of 14 rats divided into the following three groups: Group I animals (n=5) served as the intact control without treatment. Group II animals (n=5) were subjected to a surgically induced defect (2 mm, midshaft of the right femur) and implanted (IM) with TCPL capsules loaded with vancomycin (20mg) (TCPL-AB). Group III animals (n=4) were operated on in a similar fashion as Group II, and subsequently implanted with TCPL capsules loaded vancomycin (20 mg) plus statin (5 mg). The animals were euthanized at 30 days post-implantation using overdose of isoflourane. The right femurs were then harvested in addition to the vital organs, the reproductive organs, and sample of the adjacent skeletal muscles. The hard and soft tissues were evaluated histopathologically by following laboratory standard techniques. The results of this study indicated that statin plus vancomycin treated animals healed in a greater magnitude than the sham group (independent evaluators (p<0.001)). Histomorphometric analysis demonstrated that exposure to sustained delivery of statin resulted in increased in cortical width compared to the sham and control groups (p<0.05). Furthermore, the periosteal area was significantly greater than the areas observed in sham group (p<0.05). Image analysis revealed that there were more bone formation in the vancomycin and statin exposed animals than the sham. Overall, the use of TCPL system was able to deliver statin in a sustained manner without eliciting any adverse effects on the reproductive, vital organs and the muscles. In conclusion, data obtained from this study demonstrated that sustained delivery of statin resulted in a remarkable increase in osteogenic activity.