Department of Orthopedics, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box: 16635-148, Tehran, Iran; Nanotechnology Institute, Amirkabir University of Technology, P.O. Box: 15875-4413, Tehran, Iran.
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box: 16635-148, Tehran, Iran.
Mater Sci Eng C Mater Biol Appl. 2020 Jan;106:110163. doi: 10.1016/j.msec.2019.110163. Epub 2019 Sep 5.
Nanotopography and stiffness are major physical cues affecting cell fate. However, the current nanofiber modifications techniques are limited by their ability to control these two physical cues irrespective of each other without changing the materials' surface chemistry. For this reason, the isolated effects of topography and stiffness on osteogenic regulation in electrospun nanofibers have been studied incompletely. Here, we investigated 1. how functionalized multiwall carbon nanotubes (F-MWCNTs) loaded in Polycaprolactone (PCL) nanofibers control their physical properties and 2. whether the resulting unique structures lead to distinctive phenotypes in bone progenitor cells. Changes in material properties were measured by high-resolution electron microscopes, protein adsorption and tensile tests. The effect of the developed structures on human mesenchymal stem cell (MSC) osteogenic differentiation was determined by extensive quantification of early and late osteogenic marker genes. It was found that F-MWCNT loading was an effective method to independently control the PCL nanofiber surface nanoroughness or stiffness, depending on the applied F-MWCNT concentration. Collectively, this suggests that stiffness and topography activate distinct osteogenic signaling pathway. The current strategy can help our further understanding of the mechano-biological responses in osteoprogenitor cells, which could ultimately lead to improved design of bone substitute biomaterials.
纳米形貌和硬度是影响细胞命运的主要物理线索。然而，当前的纳米纤维修饰技术受到其控制这两个物理线索的能力的限制，无法在不改变材料表面化学性质的情况下将它们彼此独立地控制。出于这个原因，电纺纳米纤维中拓扑结构和硬度对成骨调节的单独影响尚未得到充分研究。在这里，我们研究了：1. 负载在聚己内酯（PCL）纳米纤维中的官能化多壁碳纳米管（F-MWCNT）如何控制其物理性质；2. 由此产生的独特结构是否会导致骨祖细胞的独特表型。通过高分辨率电子显微镜、蛋白质吸附和拉伸试验来测量材料性能的变化。通过对早期和晚期成骨标志物基因的广泛定量，确定了所开发结构对人骨髓间充质干细胞（MSC）成骨分化的影响。结果发现，F-MWCNT 负载是一种有效方法，可以根据施加的 F-MWCNT 浓度，独立控制 PCL 纳米纤维的表面纳米粗糙度或硬度。总的来说，这表明硬度和形貌激活了不同的成骨信号通路。目前的策略可以帮助我们进一步了解成骨前体细胞中的机械生物学反应，这最终可能导致改进骨替代生物材料的设计。
