International Journal of Nanomedicine (Jan 2019)
High loads of nano-hydroxyapatite/graphene nanoribbon composites guided bone regeneration using an osteoporotic animal model
Abstract
Francilio Carvalho Oliveira,1,2,* Jancineide Oliveira Carvalho,1,2,* Suziete Batista Soares Gusmão,3 Licia de Sousa Gonçalves,2 Liana Martha Soares Mendes,4 Sérgio Antonio Pereira Freitas,2 Gustavo Oliveira de Meira Gusmão,5 Bartolomeu Cruz Viana,3,6 Fernanda Roberta Marciano,1,7,8 Anderson Oliveira Lobo1,3,8 1Institute of Science and Technology, Brasil University, Itaquera 08230-030, São Paulo, Brazil; 2University Center for Health, Humanities and Technology of Piauí, (UNINOVAFAPI), Teresina, Piauí, Brazil; 3LIMAV-Interdisciplinary Laboratory for Advanced Materials, Materials Science and Engineering Graduate Program, Technological Center, UFPI-Federal University of Piauí, Teresina 64049-550, Piaui, Brazil; 4Department of Specialized Medicine, Federal University of Piauí, Teresina 64017-775, Piaui, Brazil; 5Department of Physics, State University of Piaui, Teresina 64002-150, Piaui, Brazil; 6Department of Physics, Federal University of Piauí, Teresina 64049-550, Brazil; 7Nanomedicine Lab, Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 8Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA *These authors contributed equally to this work Background: It has been difficult to find bioactive compounds that can optimize bone repair therapy and adequate osseointegration for people with osteoporosis. The nano-hydroxyapatite (nHAp)/carbon nanotubes with graphene oxides, termed graphene nanoribbons (GNR) composites have emerged as promising materials/scaffolds for bone regeneration due to their bioactivity and osseointegration properties. Herein, we evaluated the action of nHAp/GNR composites (nHAp/GNR) to promote bone regeneration using an osteoporotic model.Materials and methods: First, three different nHAp/GNR (1, 2, and 3 wt% of GNR) were produced and characterized. For in vivo analyses, 36 Wistar rats (var. albinus, weighing 250–300 g, Comissão de Ética no Uso de Animais [CEUA] n.002/17) were used. Prior to implantation, osteoporosis was induced by oophorectomy in female rats. After 45 days, a tibial fracture was inflicted using a 3.0-mm Quest trephine drill. Then, the animals were separated into six sample groups at two different time periods of 21 and 45 days. The lesions were filled with 3 mg of one of the above samples using a curette. After 21 or 45 days of implantation, the animals were euthanized for analysis. Histological, biochemical, and radiographic analyses (DIGORA method) were performed. The data were evaluated through ANOVA, Tukey test, and Kolmogorov-Smirnov test with statistical significance at P<0.05.Results: Both nHAp and GNR exhibited osteoconductive activity. However, the nHAp/GNR exhibited regenerative activity proportional to their concentration, following the order of 3% >2% >1% wt.Conclusion: Therefore, it can be inferred that all analyzed nanoparticles promoted bone regeneration in osteoporotic rats independent of analyzed time. Keywords: biomaterials, in vivo, osteoporosis, carbon nanotubes, graphene, nano-hydroxyapatite, composites