Local vanadium release from a calcium sulfate carrier accelerates fracture healing

Abstract

This study evaluated the efficacy of using calcium sulfate (CaSO4 ) as a carrier for intramedullary delivery of an organic vanadium salt, vanadyl acetylacetonate (VAC) after femoral fracture. VAC can act as an insulin-mimetic and can be used to accelerate fracture healing in rats. A heterogenous mixture of VAC and CaSO4 was delivered to the fracture site of BB Wistar rats, and mechanical testing, histomorphometry, micro-computed tomography (micro-CT) were performed to measure healing. At 4 weeks after fracture, maximum torque to failure, effective shear modulus, and effective shear stress were all significantly higher (p < 0.05) in rats treated with 0.25 mg/kg VAC-CaSO4 as compared to carrier control rats. Histomorphometry found a 71% increase in percent cartilage matrix (p < 0.05) and a 64% decrease in percent mineralized tissue (p < 0.05) at 2 weeks after fracture in rats treated with 0.25 mg/kg of VAC-CaSO4 . Micro-CT analyses at 4 weeks found a more organized callus structure and higher trending maximum connected z-ray. fraction for VAC-CaSO4 groups. Evaluation of radiographs and serial histological sections at 12 weeks did not show any evidence of ectopic bone formation. As compared to previous studies, CaSO4 was an effective carrier for reducing the dose of VAC required to accelerate femoral fracture healing in rats.