A Novel Synthetic Bone Graft Substitute for Osteoporotic Patients

Introduction: Osteoporosis is a chronic illness that affects an estimated 75 million people worldwide [1]. The risk of fracture in osteoporotic patients is greatly increased; there were an estimated 9 million osteoporotic fractures in 2000 [2]. Bone graft substitutes are commonly used in orthopaedic surgery as bone fillers and to augment fracture healing. There are currently no bone graft substitute materials specifically designed for sufferers of osteoporosis. Local administration of a drug mimic at a fracture site would allow faster integration of an implant and consequently reduce the risk of re-fracture. A novel biodegradable scaffold has been fabricated through the electrospinning process and has been modified with a novel drug mimic and is designed to act as a bone graft substitute. Materials and Methods: Polycaprolactone (PCL) fibrous scaffolds were produced by electrospinning (Electrospinning parameters: flow rate of 0.05ml/min, voltage 20kV and distance from needle to collector plate of 15cm) and treated with a novel drug mimic. Parietal bones from the calvarial of four day old mice were extracted aseptically and the scaffold was placed in a 1.5mm critical sized defect which would not heal under normal conditions. Pure PCL scaffolds were used as a control. The bone was cultured in Dulbecco's Modified Eagle Medium under standard conditions for up to six weeks. Micro-CT, energy dispersive x-ray spectroscopy and scanning electron microscopy (SEM) were performed at week one and week six.Results and Conclusions: After 6 weeks in culture Micro-CT scanning showed a significant difference in the bone fill percentages between the two scaffold types. There was a significant increase in bone formation in the parietal bone that contained the drug mimic when compared to pure PCL. This increase in bone formation can be attributed to the drug mimic having an effect on proliferating osteoblasts and increasing their activity as well as inhibiting bone resorption in neo-natal osteoclasts. SEM showed that scaffolds with the drug mimic were better integrated into the defect site. There was also an indication of rod-like hydroxyapatite precipitation at the defect site. Phosphorous and calcium levels are a good indication of bone mineralisation; energy dispersive x-ray spectroscopy showed an increase in both calcium and phosphorous levels in the presence of the drug mimic suggesting an increase in mineralisation. Previous EDX analysis has confirmed the presence of calcium ions aggregating at phosphorous rich areas, which is vital in vivo. The novel drug mimic used in this study has been shown to increase bone formation in vitro and could have the potential to act as a bone graft substitute in osteoporotic patients. References[1] European Foundation for Osteoporosis and National Osteoporosis Foundation. Osteoporos Int, 7 (1997), 1-6.[2] Johnell O, et al. Osteoporos Int, 17 (2006), 1726-1733.