He Wei, Elkhooly Tarek A, Liu Xujie, Cavallaro Alex, Taheri Shima, Vasilev Krasimir, Feng Qingling
State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.
J Mater Chem B. 2016 Feb 28;4(8):1466-1479. doi: 10.1039/c5tb02482j. Epub 2016 Feb 3.
Silver nanoparticle (AgNP) based antibacterial surfaces were fabricated using plasma polymerization technology and their effects on differentiation of human bone-marrow derived mesenchymal stem cells (hMSCs) were investigated in this study. The results showed that AgNP coated surfaces do not affect the initial adhesion, spreading and proliferation of hMSCs. Furthermore, the silver coated surface promoted adipogenic differentiation of hMSCs as demonstrated by more accumulation of lipid droplets and upregulation of adipogenesis-related genes such as peroxisome proliferator activated receptor gamma (PPARγ), adipocyte determination and differentiation factor (ADD1) and CCAAT/enhancer binding protein alpha (C/EBPα). In addition, silver incorporation activated the expression of antioxidant enzymes as a consequence of the accumulation of intracellular reactive oxygen species (ROS) in adipogenic induced cells, which was correlated with the enhanced adipogenic capacity of hMSCs. ROS generation was enhanced due to silver ion release and consequently reduced osteogenesis at the early stage after 7 days of osteogenic induction as a result of reducing alkaline phosphatase (ALP) activity. However, the differentiation and mineralization capacity of osteoblasts were restored after 14 days of osteogenic induction, which indicated that adipogenesis favors intracellular ROS accumulation mediated by silver coatings compared to osteogenesis. None of the osteogenic related genes was affected by ROS mediated by AgNP dissolution. The findings in this work are instructive for the use of silver as an antibacterial agent in the areas of tissue engineering, stem cell therapies and implantable biomedical devices.
本研究采用等离子体聚合技术制备了基于银纳米颗粒(AgNP)的抗菌表面,并研究了其对人骨髓间充质干细胞(hMSCs)分化的影响。结果表明,涂覆有AgNP的表面不影响hMSCs的初始黏附、铺展和增殖。此外,银涂层表面促进了hMSCs的成脂分化,脂质滴积累增多以及成脂相关基因如过氧化物酶体增殖物激活受体γ(PPARγ)、脂肪细胞决定和分化因子(ADD1)以及CCAAT/增强子结合蛋白α(C/EBPα)的上调证明了这一点。此外,由于成脂诱导细胞中细胞内活性氧(ROS)的积累,银的掺入激活了抗氧化酶的表达,这与hMSCs增强的成脂能力相关。由于银离子释放,ROS生成增加,因此在成骨诱导7天后的早期,由于碱性磷酸酶(ALP)活性降低,成骨作用减弱。然而,成骨诱导14天后,成骨细胞的分化和矿化能力得以恢复,这表明与成骨作用相比,成脂作用更有利于银涂层介导的细胞内ROS积累。没有一个成骨相关基因受到AgNP溶解介导的ROS的影响。这项工作中的发现对于在组织工程、干细胞治疗和可植入生物医学设备领域使用银作为抗菌剂具有指导意义。