Simvastatin and Ezetimibe-Loaded Nanofibers Administered Locally to Augment Bone Healing

Various methods have been introduced for the production of nanofibers. Electrospinning is one of the most common methods for synthesis of nanofibers, because of specific characteristics such as simple setup and mass-production ability (1). During the last decade, nanofibers have gained popularity as a drug delivery system, because of structural properties such as sustained drug release, high porosity, high surface-volume ratio, and cost-effectiveness. For these reasons, a great deal of investigations has focused on the efficacy of drug-loaded nanofibers in the treatment of different disorders (2). To date, many therapeutic agents have been loaded on nanofibers (e.g. anti-inflammatory drugs, antimicrobial drugs, anticancer drugs, cardiovascular drugs, palliative drugs, etc.), and their effectiveness has been evaluated in the treatment of different disorders (3). Bone fracture healing is a complex physiological process that involves several immune and molecular cascades, requiring delicate crosstalk between immune and bone cells. Impairment of such processes could result in fracture nonunio‎n or delayed unio‎n, which are seen in a considerable number of cases. To improve bone healing following the fracture, many strategies have been developed, including bone grafts, growth factors, and osteoconductive scaffolds (4). Even so, the rate of fracture nonunio‎n remains high; the overall risk of nonunio‎n per fracture is reported to be 1.9%, which increases to 9% in specific age groups (5). On a “best-case scenario”, cost-identification query reveals costs of £17,200 for femoral bone non-unio‎ns (6). Fracture nonunio‎n also significantly impairs the physical and mental health and quality of life (QOL) of the affected patients (7). Considering the significant economic and health burden of nonunio‎n on the patient and society, the development of more effective strategies for the prevention of unio‎n problems seems necessary (5). Lipid-lowering agents such as simvastatin have shown osteoconductive effects through inhibition of the mevalonate pathway (8). In this regard, oral statin consumption has been associated with increased bone mineralization, decreased risk of hip fracture, and promoted fracture healing (8). In a meta-analysis of randomized clinical trials, Wang et al. assessed the effects of statins on the bone mineral density of adults. Seven trials and 27,900 participants were included in this meta-analysis. According to this study, statin administration led to a significant increase in bone mineral density of participants when compared to the control group (9). The study by Lin et al. revealed the significant impact of simvastatin on reducing the risk of osteoporosis (10). These characteristics have made statin a good candidate for loading on nanofibers to be used as a bone healing substance. Subsequent investigations have shown the positive effects of local statin-loaded nanofibers in the acceleration of bone healing (11).