Effect of reactive oxygen species overproduction on osteogenesis of porous titanium implant in the present of diabetes mellitus

Clinical evidence indicates diabetes as a major risk factor for titanium implant treatment with high failure rates and poor osteointegration, but the underlying mechanism involved remains elusive. We hypothesize that reactive oxygen species (ROS) overproduction may contribute to the impaired osteogenesis of porous titanium implants (pTi) under diabetic conditions. To test this hypothesis, we cultured primary rabbit osteoblasts onto pTi and studied the cellular performance when subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and NS + H2O2(an oxidant),In-vivo performance of pTi was investigated by transplanting them intofemoral condyledefects of diabetic rabbits, which received vehicle or NAC treatment respectively. Results showed that diabetic conditions induced significant cellular apoptosis, depressed osteoblast function evidenced by impaired cell attachment and morphology, decreased cell proliferation and differentiation, and compromised in-vivo osteogenesis of pTi, while cellular ROS generation was increased derived from mitochondrial dysfunction. Scavenging ROS with NAC markedly attenuated cell apoptosis and osteoblast dysfunction, and improved bone ingrowth within pTi. Furthermore, treatment with H2O2 exerted similar adverse effect on cellular behavior as diabetes. This study furthers our knowledge on the potential role of ROS overproduction in the diabetes-induced impaired osteogenesis of titanium implants, and indicates anti-oxidative treatment as a promising strategy to promote the treatment efficacy of pTi in diabetic patients. (C) 2012 Elsevier Ltd. All rights reserved.