Controlling the Growth and Differentiation of Human Mesenchymal Stem Cells by the Arrangement of Individual Carbon Nanotubes

Abstract

Carbon nanotube (CNT) networks on solid substrates have recently drawn attention as a means to direct the growth and differentiation of stem cells. However, it is still not clear whether cells can recognize individual CNTs with a sub-2 nm diameter, and directional nanostructured substrates such as aligned CNT networks have not been utilized to control cell behaviors. Herein, we report that human mesenchymal stem cells (hMSCs) grown on CNT networks could recognize the arrangement of individual CNTs in the CNT networks, which allowed us to control the growth direction and differentiation of the hMSCs. We achieved the directional growth of hMSCs following the alignment direction of the individual CNTs. Furthermore, hMSCs on aligned CNT networks exhibited enhanced proliferation and osteogenic differentiation compared to those on randomly oriented CNT networks. As a plausible explanation for the enhanced proliferation and osteogenic differentiation, we proposed mechanotransduction pathways triggered by high cytoskeletal tension in the aligned hMSCs. Our findings provide new insights regarding the capability of cells to recognize nanostructures smaller than proteins and indicate their potential applications for regenerative tissue engineering.

Exposure to Carbon Nanotubes Leads to Changes in the Cellular Biomechanics

“…[4] Their unique properties provide a tremendous potential for applications in fields as diverse as electronics, [5] aerospace industries, [6] sensors, [7] actuators, [8] or composites. [9] Based on their properties, researchers have also been exploring CNTs potential for biological and biomedical applications as drug delivery systems, [10] substrate for cells growth in tissue regeneration, [11] therapeutic cerasela-zoica …”

“…agents, [11] or as vectors for gene transfection. [12] Such broad applications of CNTs have led to an increased production level and thus increased concerns regarding human and environmental exposure.…”

MWCNTs enhance hBMSCs spreading but delay their proliferation in the direction of differentiation acceleration

“…22 As an explanation for the enhanced proliferation and osteogenic differentiation, mechanotransduction pathways triggered by high cytoskeletal tension in the aligned hMSCs have been proposed. 23 Our results on vinculin gene expression on MWCNTs-TCP contribute to this direction. FAK and vinculin are major players in the focal adhesion processes activated by integrin-fibronectin interactions.…”

Tissue induction, the relationship between biomaterial’s microenvironment and mesenchymal stem cell differentiation

“…Previous studies found that the different micro-patterned ECM surface of biomaterial has a significant effect on the adsorption quantity of protein and life behavior of stem cells [25]. These results showed that micro-patterned size not only controls the adsorption quantity of bone growth factor protein, but also impacts on cell adhesion and morphology, as well as protein expression during the cell growth process [28]. Compared with un-micro-patterned plane biomaterials, micro-patterned surface can promote cells to secrete more type II collagen and type VI collagen, which indicates its role in regulation of cell growth [27]; On the other hand, even with the same size and shape of micro-pattern, different ECM protein micro-patterns have significant different effects on cell adhesion and protein expression.…”