Stem cells could regulate their fate by responding to physical signals from their microenvironment. Recently, a few studies have shown that the spontaneous osteogenic differentiation of mesenchymal stem cells (MSCs) could occur on surfaces with nanoscaled structures (e.g., nanotubes and nanopits), which is essentially useful when designing biomaterial scaffolds for bone tissue engineering applications. However, the osteogenic nanotopography has not been widely investigated and the osteogenic mechanism of surfaces is still not well understood. In this study, oriented nanograting‐like surfaces are fabricated by stretching the nanoholed inverse opal films, which are made through a convenient bottom‐up approach of the self‐assembly of colloidal nanoparticles. The effect of different surface nanotopography on the osteogenic differentiation of rat bone marrow‐derived MSCs (rBMSCs) is examined in the absence of osteogenic inducing media and the underlying mechanisms are investigated using immunofluorescence staining and quantitative real‐time polymerase chain reaction (PCR) analysis. It is found that rBMSCs on the oriented nanograting‐like surfaces show significantly higher expression levels of osteogenic genes and more phosphorylation of Smad1/5, extracellular signal‐regulated kinases (ERKs), and p38, confirming the activation of Smad and mitogen‐activated protein kinase signaling pathways in the nanotopography‐induced osteogenesis. Thus, the oriented nanograting‐like surface nanotopography may provide a new strategy for the surface design of biomaterial scaffolds in bone tissue engineering.
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