Wu Yuehao, Wu Jinjie, Huang Xu, Zhu Xiupeng, Zhi Wei, Wang Jianxin, Sun Dong, Chen Xuening, Zhu Xiangdong, Zhang Xingdong
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, Sichuan, China.
Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Mater Today Bio. 2023 Dec 2;23:100891. doi: 10.1016/j.mtbio.2023.100891. eCollection 2023 Dec.
The strategy of coupling the micro-vibration mechanical field with Ca/P ceramics to optimize the osteogenic microenvironment and enhance the functional activity of the cells can significantly improve the bone regeneration of the graft. However, the regulation mode and mechanism of this coupling strategy are not fully understood at present. This study investigated the influence of different waveforms of the electrical signals driving Microvibration Stimulation (MVS) on this coupling effect. The results showed that there were notable variances in calcium phosphate dissolution and redeposition, protein adsorption, phosphorylation of ERK1/2 and FAK signal pathways and activation of calcium channels such as TRPV1/Piezo1/Piezo2 in osteogenic microenvironment under the coupling action of hydroxyapatite (HA) ceramics and MVS driven by different electrical signal waveforms. Ultimately, these differences affected the osteogenic differentiation process of cells by a way of time-sequential regulation. Square wave-MVS coupled with HA ceramic can significantly delay the high expression time of characteristic genes (such as Runx2, Col-I and OCN) in MC3T3-E1 cells during the early, middle and late stage of differentiation, while maintain the high proliferative activity of MC3T3-E1 cells. Triangle wave signal-MVS coupled with HA ceramic promoted the osteogenic differentiation of cells in the early and late stages. Sine wave-MVS shows the effect on the process of osteogenic differentiation in the middle stage (such as the up-regulation of ALP synthesis and Col-I gene expression in the early stage of stimulation). In addition, Square wave-MVS showed the best coupling effect. The bone graft constructed under square wave-MVS formed new bone tissue and mature blood vessels only 2 weeks after subcutaneous implantation in nude mice. Our study provides a new non-invasive regulation model for precisely optimizing the osteogenic microenvironment, which can accelerate bone regeneration in bone grafts more safely, accurately and reliably.
将微振动机械场与钙磷陶瓷相结合以优化成骨微环境并增强细胞功能活性的策略，可显著改善移植物的骨再生。然而，目前对这种耦合策略的调控方式和机制尚未完全了解。本研究探讨了驱动微振动刺激（MVS）的电信号不同波形对这种耦合效应的影响。结果表明，在羟基磷灰石（HA）陶瓷与不同电信号波形驱动的MVS耦合作用下，成骨微环境中磷酸钙的溶解与再沉积、蛋白质吸附、ERK1/2和FAK信号通路的磷酸化以及TRPV1/Piezo1/Piezo2等钙通道的激活存在显著差异。最终，这些差异通过时序调控的方式影响细胞的成骨分化过程。方波-MVS与HA陶瓷耦合可显著延迟MC3T3-E1细胞在分化早、中、晚期特征基因（如Runx2、Col-I和OCN）的高表达时间，同时维持MC3T3-E1细胞的高增殖活性。三角波信号-MVS与HA陶瓷耦合促进细胞在早期和晚期的成骨分化。正弦波-MVS在中期对成骨分化过程有影响（如在刺激早期上调ALP合成和Col-I基因表达）。此外，方波-MVS显示出最佳的耦合效果。在方波-MVS作用下构建的骨移植物在裸鼠皮下植入仅2周后就形成了新骨组织和成熟血管。我们的研究提供了一种新的非侵入性调控模型，用于精确优化成骨微环境，能够更安全、准确和可靠地加速骨移植物中的骨再生。
