Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu 610031, China.
J Mater Chem B. 2020 May 21;8(19):4278-4288. doi: 10.1039/d0tb00223b. Epub 2020 Apr 20.
The bone defects caused by trauma and disease have become a major difficulty in the treatment of clinical bone defects, and bone tissue engineering has become a promising treatment strategy. It was found that mechanical stimulation regulated the development of bone constructs by affecting the distribution and differentiation of cells on them. In this study, tissue-engineered bone grafts with enhanced bioactivity and self-adaptability were constructed by BMSCs and biphasic calcium phosphate (BCP) scaffolds under periodic micro-vibration stimulation (MVS) with a frequency of 40 Hz and a magnitude of 0.3 g. The results of the material characterization indicated that the BCP scaffolds created a more favourable osteogenic micro-environment with promoted calcium ion release, protein adsorption and mineralization deposition under the micro-vibration stimulation. The in vitro results showed that the apoptosis of BMSCs increased significantly on day 1, but from day 3 on, the proliferation increased and apoptosis decreased. Cells were evenly distributed on the scaffolds, exhibiting tight adhesion in a flat-shape and distinct matrix mineralization. F-actin and ALP expression significantly increased and meanwhile osteogenesis-related genes including Runx2, Col-I, ALP, and OCN were significantly up-regulated. Western blotting results suggested that the ERK1/2 and Wnt/β-catenin signalling pathways were involved in the osteogenic behaviour of BMSCs induced by MVS. In vivo experiments showed that grafts had stronger osteoinduction and mechanical adaptability. Taken together, this study suggested that micro-vibration stimulation combined with BCP scaffolds with good osteoinduction could be a promising approach for constructing tissue engineered bone grafts with enhanced bioactivity, mechanical adaptability, and bone regeneration repair capability.
创伤和疾病引起的骨缺损已成为临床骨缺损治疗的一大难题，而骨组织工程已成为一种有前途的治疗策略。研究发现，机械刺激通过影响细胞在其上的分布和分化来调节骨构建体的发育。在这项研究中，通过周期性微振动刺激（频率为 40 Hz，幅度为 0.3 g），用 BMSCs 和双相钙磷（BCP）支架构建了具有增强的生物活性和自适应性的组织工程化骨移植物。材料特性的结果表明，BCP 支架在微振动刺激下创造了更有利的成骨微环境，促进了钙离子释放、蛋白质吸附和矿化沉积。体外结果表明，BMSCs 的细胞凋亡在第 1 天显著增加，但从第 3 天开始，增殖增加，凋亡减少。细胞均匀分布在支架上，呈扁平状紧密附着，基质矿化明显。F-肌动蛋白和碱性磷酸酶表达显著增加，同时成骨相关基因包括 Runx2、Col-I、ALP 和 OCN 也显著上调。Western blot 结果表明，ERK1/2 和 Wnt/β-catenin 信号通路参与了 MVS 诱导的 BMSCs 成骨行为。体内实验表明，移植物具有更强的成骨诱导和机械适应性。总之，这项研究表明，微振动刺激与具有良好成骨诱导能力的 BCP 支架相结合，可能是构建具有增强生物活性、机械适应性和骨再生修复能力的组织工程化骨移植物的一种有前途的方法。
