Safety and Osteointegration of Titanium Screws Coated with a Fibroblast Growth Factor-2-Calcium Phosphate Composite Layer in Non-Human Primates: A Pilot Study.

Spinal instrumentation surgery for older patients with osteoporosis is increasing. Implant loosening may occur due to inappropriate fixation in osteoporotic bone. Developing implants that achieve stable surgical results, even in osteoporotic bone, can reduce re-operation, lower medical costs, and maintain the physical status of older patients. Fibroblast growth factor-2 (FGF-2) promotes bone formation; thus, coating pedicle screws with an FGF-2-calcium phosphate (FGF-CP) composite layer is hypothesized to enhance osteointegration in spinal implants. We designed a long-term implantation pilot study that estimated the safety and bone-forming efficacy of pedicle screws coated with an FGF-CP composite layer in cynomolgus monkeys. Titanium alloy screws, either uncoated (controls) or aseptically coated with an FGF-CP composite layer, were implanted in the vertebral bodies of six female adult cynomolgus monkeys (three monkeys per group) for 85 days. Physiological, histological, and radiographic investigations were performed. There were no serious adverse events, and no radiolucent areas were observed around the screws in either group. The bone apposition rate in the intraosseous region was significantly higher in the FGF-CP group than in the controls. Moreover, as analyzed by Weibull plots, the bone formation rate of the FGF-CP group exhibited a significantly higher regression line slope than the control group. These results demonstrated that there was significantly less risk of impaired osteointegration in the FGF-CP group. Our pilot study suggests that FGF-CP-coated implants could promote osteointegration, be safe, and reduce the probability of screw loosening.