Jia Tan1,2, Jiaxin Li3, Bojun Cao1,2, Junxiang Wu1,2, Dinghao Luo1,2, Zhaoyang Ran1,2, Liang Deng1,2, Xiaoping Li4, Wenbo Jiang2, Kai Xie1,2, Lei Wang1,2, Yongqiang Hao1,2. 1. Shanghai Key Laboratory of Orthopaedic Implants Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China. 2. Clinical and Translational Research Center for 3D Printing Technology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Jin Zun Road No. 115, 200011, Shanghai, China. 3. Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China. 4. Ningxia Orient Ta Ind Co, 119, Yejin Road, Dawukou District, Shizuishan, Ningxia, 753000, PR China.
Abstract
Background: Stable fixation is crucial in fracture treatment. Currently, optimal fracture fixation devices with osteoinductivity, mechanical compatibility, and corrosion resistance are urgently needed for clinical practice. Niobium (Nb), whose mechanical properties are similar to those of bone tissue, has excellent biocompatibility and corrosion resistance, so it has the potential to be the most appropriate fixation material for internal fracture treatment. However, not much attention has been paid to the use of Nb in the area of clinical implants. Yet its role and mechanism of promoting fracture healing remain unclear. Hence, this study aims at elucidating on the effectiveness of Nb by systematically evaluating its osteogenic performance via in vivo and ex vivo tests. Methods: Systematic in vivo and in vitro experiments were conducted to evaluate the osteogenic properties of Nb. In vitro experiments, the biocompatibility and osteopromoting activity of Nb were assessed. And the osteoinductive activity of Nb was assessed by alizarin red, ALP staining and PCR test. In vivo experiments, the effectiveness and biosafety of Nb in promoting fracture healing were evaluated using a rat femoral fracture model. Through the analysis of gene sequencing results of bone scab tissues, the upregulation of PI3K-Akt pathway expression was detected and it was verified by histochemical staining and WB experiments. Results: Experiments in this study had proved that Nb had excellent in-vitro cell adhesion and proliferation-promoting effects without cytotoxicity. In addition, ALP activity, alizarin red staining and semi-quantitative analysis in the Nb group had indicated its profound impact on enhancing osteogenic differentiation of MC3T3-E1 cells. We also found that the use of Nb implants can accelerate fracture healing compared to that with Ti6Al4V using an animal model of femur fracture in rats, and the biosafety of Nb was confirmed in vivo via histological evaluation. Furthermore, we found that the osteogenic effects of Nb were achieved through activation of the PIK/Akt3 signalling pathway. Conclusion: As is shown in the present research, Nb possessed excellent biosafety in clinical implants and accelerated fracture healing by activating the PI3K-Akt signalling pathway, which had good prospects for clinical translation, and it can replace titanium alloy as a material for new functional implants.
Background: Stable fixation is crucial in fracture treatment. Currently, optimal fracture fixation devices with osteoinductivity, mechanical compatibility, and corrosion resistance are urgently needed for clinical practice. Niobium (Nb), whose mechanical properties are similar to those of bone tissue, has excellent biocompatibility and corrosion resistance, so it has the potential to be the most appropriate fixation material for internal fracture treatment. However, not much attention has been paid to the use of Nb in the area of clinical implants. Yet its role and mechanism of promoting fracture healing remain unclear. Hence, this study aims at elucidating on the effectiveness of Nb by systematically evaluating its osteogenic performance via in vivo and ex vivo tests. Methods: Systematic in vivo and in vitro experiments were conducted to evaluate the osteogenic properties of Nb. In vitro experiments, the biocompatibility and osteopromoting activity of Nb were assessed. And the osteoinductive activity of Nb was assessed by alizarin red, ALP staining and PCR test. In vivo experiments, the effectiveness and biosafety of Nb in promoting fracture healing were evaluated using a rat femoral fracture model. Through the analysis of gene sequencing results of bone scab tissues, the upregulation of PI3K-Akt pathway expression was detected and it was verified by histochemical staining and WB experiments. Results: Experiments in this study had proved that Nb had excellent in-vitro cell adhesion and proliferation-promoting effects without cytotoxicity. In addition, ALP activity, alizarin red staining and semi-quantitative analysis in the Nb group had indicated its profound impact on enhancing osteogenic differentiation of MC3T3-E1 cells. We also found that the use of Nb implants can accelerate fracture healing compared to that with Ti6Al4V using an animal model of femur fracture in rats, and the biosafety of Nb was confirmed in vivo via histological evaluation. Furthermore, we found that the osteogenic effects of Nb were achieved through activation of the PIK/Akt3 signalling pathway. Conclusion: As is shown in the present research, Nb possessed excellent biosafety in clinical implants and accelerated fracture healing by activating the PI3K-Akt signalling pathway, which had good prospects for clinical translation, and it can replace titanium alloy as a material for new functional implants.
Authors: Kazuhisa Nakashima; Xin Zhou; Gary Kunkel; Zhaoping Zhang; Jian Min Deng; Richard R Behringer; Benoit de Crombrugghe Journal: Cell Date: 2002-01-11 Impact factor: 41.582
Authors: J F Bartolomé; J S Moya; R Couceiro; C F Gutiérrez-González; F Guitián; A Martinez-Insua Journal: Biomaterials Date: 2015-10-27 Impact factor: 12.479