Cao Wanxu, Lin Weimin, Cai Hanxu, Chen Yafang, Man Yi, Liang Jie, Wang Qiguang, Sun Yong, Fan Yujiang, Zhang Xingdong
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu, China.
State Key Laboratory of Oral Diseases, Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Regen Biomater. 2019 Mar;6(2):99-106. doi: 10.1093/rb/rbz005. Epub 2019 Feb 4.
Mechanical signals have been played close attention to regulate chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, dynamic mechanical loading simulation with natural frequencies and intensities were applied to the 3D cultured BMSCs-collagen scaffold constructs. We investigated the effects of dynamic mechanical loading on cell adhesion, uniform distribution, proliferation, secretion of extracellular matrix (ECM) and chondrogenic differentiation of BMSCs-collagen scaffold constructs. The results indicated that dynamic mechanical loading facilitated the BMSCs adhesion, uniform distribution, proliferation and secretion of ECM with a slight contraction, which significantly improved the mechanical strength of the BMSCs-collagen scaffold constructs for better mimicking the structure and function of a native cartilage. Gene expression results indicated that dynamic mechanical loading contributed to the chondrogenic differentiation of BMSCs with higher levels of AGG, COL2A1 and SOX9 genes, and prevented of hypertrophic process with lower levels of COL10A1, and reduced the possibility of fibrocartilage formation due to down-regulated COL1A2. In conclusion, this study emphasized the important role of dynamic mechanical loading on promoting BMSCs chondrogenic differentiation and maintaining the cartilage phenotype for reconstruction of tissue-engineered cartilage, which provided an attractive prospect and a feasibility strategy for cartilage repair.
机械信号在调节骨髓间充质干细胞(BMSCs)的软骨形成分化方面已受到密切关注。在本研究中,将具有自然频率和强度的动态机械加载模拟应用于三维培养的BMSCs - 胶原蛋白支架构建体。我们研究了动态机械加载对BMSCs - 胶原蛋白支架构建体的细胞黏附、均匀分布、增殖、细胞外基质(ECM)分泌以及软骨形成分化的影响。结果表明,动态机械加载促进了BMSCs的黏附、均匀分布、增殖和ECM分泌,并伴有轻微收缩,这显著提高了BMSCs - 胶原蛋白支架构建体的机械强度,从而更好地模拟天然软骨的结构和功能。基因表达结果表明,动态机械加载有助于BMSCs的软骨形成分化,使AGG、COL2A1和SOX9基因水平升高,通过降低COL10A1水平防止肥大过程,并因COL1A2下调而降低纤维软骨形成的可能性。总之,本研究强调了动态机械加载在促进BMSCs软骨形成分化和维持软骨表型以用于组织工程软骨重建方面的重要作用,为软骨修复提供了诱人的前景和可行的策略。