Niobium promotes fracture healing in rats by regulating the PI3K-Akt signalling pathway: An in vivo and in vitro study

铌通过调节 PI3K-Akt 信号通路促进大鼠骨折愈合:一项体内和体外研究

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作者:Jia Tan, Jiaxin Li, Bojun Cao, Junxiang Wu, Dinghao Luo, Zhaoyang Ran, Liang Deng, Xiaoping Li, Wenbo Jiang, Kai Xie, Lei Wang, Yongqiang Hao

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.

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.

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

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.

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