Pamidronate-Encapsulated Electrospun Polycaprolactone-Based Composite Scaffolds for Osteoporotic Bone Defect Repair

Bone fractures associated with osteoporosis are a major concern all over the world especially among the elderly population and postmenopausal women. Bisphosphonates (BPs) are widely used clinically for both treatment and prevention of osteoporosis despite their poor oral bioavailability and undesired side effects. Local delivery of BPs from polymeric scaffolds can improve the efficacy and overcome the undesirable side effects associated with oral bisphosphonate therapy. The aim of the present study is to explore the effectiveness of pamidronate (PDS) encapsulated electrospun polycaprolactone/polycaprolactone-polyethyleneglycol-polycaprolactone/nanohydroxyapatite (PCH) scaffolds in healing critical-size calvarial defects in an osteoporotic rat animal model. Prior to implantation studies, the effect of PDS on the fiber architecture, mechanical properties, and in vitro degradation behavior was evaluated. The in vitro release of PDS from PCH scaffolds in phosphate buffer saline (PBS) at 37 °C was monitored for a period of 21 days. An osteoporotic animal model was successfully developed in Wistar rats by bilateral ovariectomy. Results of micro CT (computed tomography) and blood serum analysis confirmed the osteoporotic model induction in rats. Critical-size calvarial defects of 8 mm size were created in osteoporotic rats, and the in vivo osteogenic efficacy of PCH-PDS scaffolds was evaluated by micro CT, histology, and histomorphometry. Micro CT analysis showed improved osseous tissue integration with the use of PDS-loaded PCH scaffolds after 12 week post implantation. Histology, density measurement using micro CT, and histomorphometry further substantiate that PCH-PDS scaffolds have the potential to be used for the repair of osteoporotic bone defects. Our findings revealed that incorporation of PDS onto PCH scaffolds provides a promising biomaterial that could be used for regenerating osteoporosis-related fractures.