Critical Long Bone Defect Treated by Magnetic Scaffolds and Fixed by Permanent Magnets

Diaphyseal bone defect represents a significant problem for orthopaedic surgeons and patients. In order to improve and fasten bone regenerating process we implanted HA biodegradable magnetized scaffolds in a large animal model critical bone defect. A critical long bone defect was created in 6 sheep metatarsus diaphysis; then we implanted a novel porous ceramic composite scaffold (20.0 mm in length; 6.00 mm inner diameter and 17.00 mm outer diameter), made of Hydroxyapatite that incorporates magnetite (HA/Mgn 90/10), proximally fixated by two small cylindrical permanent parylene coated NdFeB magnets (one 6.00 mm diameter magnetic rod firmly incorporated into the scaffold and one 8.00 mm diameter magnetic rods fitted into proximal medullary canal, both 10.00 mm long); to give stability to the complex bone-scaffold-bone, screws and plate was used as a bridge. Scaffolds biocompatibility was previously assessed in vitro using human osteoblast-like cells. Magnetic forces through scaffold were calculated by finite element software (COMSOL Multiphysics, AC/DC Model). One week after surgery, magnetic nanoparticles functionalized with vascular endothelial growth factor (VEGF) were injected at the mid portion of the scaffold using a cutaneous marker positioned during surgery as reference point. After sixteen weeks, sheep were sacrificed to analyze metatarsi. Macroscopical, radiological and microCT examinations were performed. Macroscopical examination shows bone tissue formation inside scaffold pores and with complete coverage of scaffolds, in particular at magnetized bone-scaffold interface. X-rays show a good integration of the scaffold with a good healing process of critical bone defect, and without scaffolds mobilization. These datas were confirmed by the microCT that shown new formation of bone inside the scaffolds, in particular at magnetized bone-scaffold interface. These preliminary results lead our research to exploiting magnetic forces to stimulate bone formation, as attested in both in vitro and in vivo models and to improve fixation at bone scaffold interface, as calculated by finite element software, and moreover to guide targeted drug delivery without functionalized magnetic nanoparticles dissemination in all body. Histological analysis will be performed to confirm and quantify bone tissue regeneration at both interfaces.