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

Abstract

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.

Screw Osteointegration—Increasing Biomechanical Resistance to Pull-Out Effect

“…One of the most commonly employed cement augmentation methods is the polymethylmethacrylate (PMMA) injection. PMMA significantly increases the axial pull-out strength of augmented pedicle screws in both primary and revision procedures, being a valuable technique for reinforcing the bone–screw interface [ 9 , 40 , 60 ]. Despite being widely used in orthopedic surgery, PMMA cement augmentation had a delayed adoption in spinal surgery due to a series of risks.…”

“…Despite being widely used in orthopedic surgery, PMMA cement augmentation had a delayed adoption in spinal surgery due to a series of risks. The main problems with using this type of cement are the possibility of thermal necrosis caused by the exothermic polymerization reaction of PMMA, the risk of neural injury in case of polymer extravasation, and challenges in performing revision surgery [ 9 , 40 , 41 , 61 ]. In more detail, the leakage of PMMA into the spinal canal may produce permanent thermal damage to the spinal cord, while the non-biodegradable nature of this polymer translates into a lasting stenosing mass left in the spinal canal in the event of extravasation [ 40 ].…”

“…Since then, ensuring the mechanical stability of the spine has become a must for obtaining successful surgical outcomes, with scientists developing more and more varied and effective orthopedical implants [ 2 , 7 , 8 ]. Utilizing internal fixation systems, such as screws, rigid rods, plates, wires, and cages, is vital for stabilizing the spine’s structure, restoring its endurance, and protecting its function [ 2 , 5 , 6 , 9 , 10 ].…”

“…With spinal instrumentation at hand, spinal surgery represents a challenging treatment approach for spinal diseases, supposing the utilization of complex spinal fixation constructs and prolonged operative times. Moreover, performing spinal surgery on patients with osteoporosis is even more difficult, as these people are prone to perioperative complications which may also result in mechanical failures, such as screw pull-out or loosening [ 7 , 9 , 11 , 12 ]. A proper selection of fixation devices is mandatory to avoid procedure failure and eliminate the necessity of revision surgeries.…”

Potential of Titanium Pins Coated with Fibroblast Growth Factor-2–Calcium Phosphate Composite Layers to Reduce the Risk of Impaired Bone–Pin Interface Strength in the External Fixation of Distal Radius Fractures

“…We developed titanium (Ti) screws coated with human recombinant fibroblast growth factor (FGF)-2–calcium phosphate (CP) composite layers by immersing them in an infusion fluid-based supersaturated CP solution containing FGF-2 at 37 °C for 48 h [ 8 ]. The risk of impaired bone apposition to the screw was analyzed using Weibull plot analysis, a method commonly employed to analyze the lifetime, failure probability or risk, and reliability of industrial products [ 9 ].…”