Diaphyseal bone defect represents a significant problem for orthopaedic surgeons and patients. Bone is a complex tissue whose structure and function depend strictly on ultrastructural organization of its components: cells, organic (extracellular matrix, ECM) and inorganic components. The purpose of this study was to evaluate bone regeneration in a critical diaphyseal defect treated by implantation of a magnetic scaffold fixed by hybrid system (magnetic and mechanical), supplied through nanoparticle-magnetic (MNP) functionalized with Vascular Endothelial-Growth-Factor-(VEGF) and magnetic-guiding. A critical long bone defect was created in 8 sheep metatarsus diaphysis: it was 20.0 mm in length; the medullary canal was reamed till 8.00 mm of inner diameter. Then a 8.00 mm diameter magnetic rod was fitted into proximal medullary canal (10 mm in length). After that a scaffold made of Hydroxyapatite (outer diameter 17.00 mm) that incorporates magnetite (HA/Mgn 90/10) was implanted to fill critical long bone defect. A magnetic rod (6.00 mm diameter) was firmly incorporated at proximal side into the scaffold. Both magnets had 10 mm length. To give stability to the complex bone-scaffold-bone a plate was used as a bridge; it was fixed proximally by 2 screws and distally by 3 screws. 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 VEGF were injected at the mid portion of the scaffold using a cutaneous marker positioned during surgery as reference point in 4 sheep; other sheep were used as control group. After sixteen weeks, sheep were sacrificed to analyze metatarsi. Macroscopical, radiological and microCT examinations were performed.Introduction
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