Significant effect of simvastatin and/or ezetimibe-loaded nanofibers on the healing of femoral defect: An experimental study

Fracture healing complications are associated with significant healthcare and economic burden. In this study, we aimed to investigate how the combined administration of local simvastatin and ezetimibe into the femoral defect of the animal model affects the bone-healing process in comparison with their monotherapy. A total of 32 four-month-old adult male Wistar rats were randomized into the four study groups: simvastatin + ezetimibe-loaded nanofibers (group 1), simvastatin-loaded nanofibers (group 2), ezetimibe-loaded nanofibers (group 3), and non-loaded nanofibers (group 4). After the generation of femoral defects, the predesigned nanofibers were locally administered into the defect site. The healing measures were serum and bone osteoprotegerin (OPG) expression, pathologic evaluation of union (Allen's fracture healing scores), and radiographic evaluation of bone density (Hounsfield scale) at weeks 2 and 4. The improvement of all evaluated healing measures was remarkably superior in rats that were treated with loaded nanofibers in comparison with the control group. Also, the improvement of all evaluated healing measures was considerably more in the simvastatin-ezetimibe combination therapy group compared to their monotherapy. All the evaluated measures were superior in the ezetimibe monotherapy group compared to the simvastatin monotherapy group. The cumulative effect of simvastatin and ezetimibe on the induction of bone healing is more significant than the individual effect of these drugs. Therefore, local administration of nanofibers loaded with simvastatin and ezetimibe could be regarded as a promising osteoinductive compound for the acceleration of bone repair.