Nanohydroxyapatite/Graphene Nanoribbons Nanocomposites Induce in Vitro Osteogenesis and Promote in Vivo Bone Neoformation

Joelson S. Medeiros, Aureliano M. Oliveira, Jancineide O. de Carvalho, Ritchelli Ricci, Maria do C. C. Martins, Bruno V. M. Rodrigues, Thomas J. Webster, Bartolomeu C. Viana, Luana M. R. Vasconcellos, Renata A. Canevari, Fernanda R. Marciano, Anderson O. Lobo

Index: 10.1021/acsbiomaterials.7b01032

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Abstract

Nanomaterials based on graphene oxide nanoribbons (GNR) and nanohydroxyapatite (nHAp) serve as attractive materials for bone tissue engineering. Herein, we evaluated the potential of nHAp/GNR toward in vitro analysis of specific genes related to osteogenesis and in vivo bone regeneration using animal model. Three different concentrations of nHAp/GNR composites were analyzed in vitro using a cytotoxicity assay, and osteogenic potential was determined by ALP, OPN, OCN, COL1, and RUNX2 genes and alkaline phosphatase assays. In vivo bone neoformation using a well-established in vivo rat tibia defect model was used to confirm the efficiency of the optimized composite. The scaffolds were nontoxic, and the osteogenesis process was dose-dependent (at 200 μg mL–1 of nHAp/GNR) compared to controls. The in vivo results showed higher bone neoformation after 15 days of nHAp/GNR implantation compared to all groups. After 21 days, both nHAp/GNR composites showed better lamellar bone formation compared to control. We attributed this enhanced bone neoformation to the high bioactivity and surface area presented by nHAp/GNR composites, which was systematically evaluated in previous studies. These new in vivo results suggest that nHAp/GNR composites can be exploited for a range of strategies for the improved development of novel dental and orthopedic bone grafts to accelerate bone regeneration.