Ozawa Ryotaro, Saita Makiko, Sakaue Sho, Okada Ryusaku, Sato Takenori, Kawamata Ryota, Sakurai Takashi, Hamada Nobushiro, Kimoto Katsuhiko, Nagasaki Yukio
Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, Kanagawa, Japan.
Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
Acta Biomater. 2020 Jul 1;110:82-94. doi: 10.1016/j.actbio.2020.04.003. Epub 2020 Apr 27.
Dental implant surgery is a routine treatment in clinical dentistry. However, implant surgery is associated with an increased risk of bacterially induced peri-implantitis and the production of reactive oxygen species (ROS), with no established treatment. We recently designed a new redox injectable gel (RIG) containing nitroxide radicals for the treatment of peri-implantitis. Here, we investigated the antioxidative effect of RIG as a preventive therapy for ROS-associated peri-implantitis in a rat model of alveolar bone resorption and in vitro. In each rat, the maxillary first molar tooth was replaced with a screw-type implant, and rats were assigned to one of four groups: an implant alone, an implant with infection, implant with infection and treatment with nRIG (a non-nitroxide radical-containing injectable hydrogel) or RIG. We confirmed the long-term retention of RIG in the peri-implant region and found that RIG significantly protected the alveolar bone volume and decreased lipid peroxidation. In culture, we found that RIG restored osteoblast proliferation and differentiation in the presence of hydrogen peroxide (HO)-induced oxidative stress. Moreover, using a malondialdehyde assay of lipid peroxidation, we found that RIG suppressed oxidative stress in HO-treated rat osteoblasts. Overall, RIG is anticipated as a prophylactic treatment for peri-implantitis and may help preserve oral function. Statement of Significance 1. Implant surgery is associated with an increased risk of bacterially induced peri-implantitis and the production of reactive oxygen species (ROS). We designed a novel redox injectable gel (RIG) containing nitroxide radicals for the treatment of peri-implantitis. In this study, we investigated the antioxidative effect of RIG as a preventive therapy for ROS-associated peri-implantitis in a rat model and in vitro. 2. We showed that treatment with RIG reduces oxidative damage in a rat peri-implantitis model, protecting against bone resorption and a loss of bone density. We showed that RIG inhibits HO-mediated decreases in proliferation, osteoblast differentiation, and mineralization, and also against lipid peroxidation in vitro. Our results indicate that RIG has an antioxidative effect of peri-implantitis.
牙种植手术是临床牙科的常规治疗方法。然而,种植手术会增加细菌诱导的种植体周围炎和活性氧(ROS)产生的风险,且尚无成熟的治疗方法。我们最近设计了一种含氮氧自由基的新型氧化还原可注射凝胶(RIG)用于治疗种植体周围炎。在此,我们在大鼠牙槽骨吸收模型和体外研究了RIG作为与ROS相关的种植体周围炎预防性治疗的抗氧化作用。在每只大鼠中,用上颌第一磨牙替换为螺旋型种植体,并将大鼠分为四组之一:仅种植体组、感染种植体组、感染种植体并用nRIG(不含氮氧自由基的可注射水凝胶)治疗组或RIG治疗组。我们证实了RIG在种植体周围区域的长期留存,并发现RIG显著保护牙槽骨体积并减少脂质过氧化。在培养中,我们发现RIG在过氧化氢(HO)诱导的氧化应激存在下恢复了成骨细胞的增殖和分化。此外,通过脂质过氧化的丙二醛测定,我们发现RIG抑制了HO处理的大鼠成骨细胞中的氧化应激。总体而言,RIG有望作为种植体周围炎的预防性治疗方法,并可能有助于保持口腔功能。重要性声明1. 种植手术会增加细菌诱导的种植体周围炎和活性氧(ROS)产生的风险。我们设计了一种含氮氧自由基的新型氧化还原可注射凝胶(RIG)用于治疗种植体周围炎。在本研究中,我们在大鼠模型和体外研究了RIG作为与ROS相关的种植体周围炎预防性治疗的抗氧化作用。2. 我们表明,RIG治疗可减少大鼠种植体周围炎模型中的氧化损伤,防止骨吸收和骨密度丧失。我们表明,RIG在体外抑制HO介导的增殖、成骨细胞分化和矿化的降低,以及脂质过氧化。我们的结果表明RIG对种植体周围炎具有抗氧化作用。