Simvastatin Loaded Nano Hydroxyapatite in Bone Regeneration: A Study in the Rabbit Femoral Condyle

Abstract

Background: Enhancement of the bone regenerative capacity of the bone substitutes could be achieved by incorporating bioactive agents such as proteins, and different drugs. Simvastatin, an inhibitor of cholesterol synthesis, stimulates bone formation by enhancing the expression of Bone Morphogenetic Protein-2 (BMP-2) in osteoblasts. Objective: The objective of the study is to evaluate bone regeneration following simvastatin loaded nano-hydroxyapatite scaffold in the bone defect created on the femoral condyle of rabbits. Methods: Twelve adult, New Zealand white rabbits were used in the study. Twenty-four defects of size 5x8 mm were created on the lateral aspect of the femoral condyle. The defects were filled with either Nano-Hydroxyapatite (nHA) particles alone or nHA with Simvastatin (SIM). The condyles were retrieved after 8 weeks and analyzed using micro CT and histology. Results: The Bone Mineral Density (BMD) was significantly higher for the defects filled with SIM loaded nHA compared to the nHA site. Micro CT showed a significantly higher bone volume in the defects filled with Simvastatin loaded site compared to the control site. Quantitative analysis of the histologic sections also showed significantly higher bone volume in the defects filled with SIM loaded nHA (57.2±4.8) compared to nHA alone (50.1±5.5). Conclusion: Based on the results, it can be concluded that local delivery of simvastatin enhanced the bone regeneration in rabbit femoral condyle. Simvastatin could be used as an activator to enhance bone regeneration in bone defects along with hydroxyapatite ceramics.