Nanotopography Drives Stem Cell Fate Toward Osteoblast Differentiation Through α1β1 Integrin Signaling Pathway

Abstract

The aim of our study was to investigate the osteoinductive potential of a titanium (Ti) surface with nanotopography, using mesenchymal stem cells (MSCs) and the mechanism involved in this phenomenon. Polished Ti discs were chemically treated with H2 SO4 /H2 O2 to yield nanotopography and rat MSCs were cultured under osteogenic and non-osteogenic conditions on both nanotopography and untreated polished (control) Ti surfaces. The nanotopography increased cell proliferation and alkaline phosphatase (Alp) activity and upregulated the gene expression of key bone markers of cells grown under both osteogenic and non-osteogenic conditions. Additionally, the gene expression of α1 and β1 integrins was higher in cells grown on Ti with nanotopography under non-osteogeneic condition compared with control Ti surface. The higher gene expression of bone markers and Alp activity induced by Ti with nanotopography was reduced by obtustatin, an α1β1 integrin inhibitor. These results indicate that α1β1 integrin signaling pathway determines the osteoinductive effect of nanotopography on MSCs. This finding highlights a novel mechanism involved in nanosurface-mediated MSCs fate and may contribute to the development of new surface modifications aiming to accelerate and/or enhance the process of osseointegration.

Bone tissue response to plasma-nitrided titanium implant surfaces

“…Several Ti surface modifications have been proposed in order to improve the process of implant osseointegration 1 , 2 , 6 , 14 , 15 , 17 , 20 . As plasma-nitrided Ti surfaces favor osteoblast differentiation, here, we have investigated bone tissue response to these surfaces and compared with machined ones.…”

“…It has been observed that Ti with nanotopography favors osteoblast differentiation in several culture models 14 , 17 , 20 . Also, biological coatings such as bone apatite and type I collagen enhance bone formation in contact with Ti implants 6 , 25 .…”

Stem cell responses to nanotopography

“…Additionally, α1 and β1 integrin gene expression was higher in cells grown on nanotopography under nonosteogenic conditions compared with those on a control Ti surface. The higher osteogenic gene expression induced by Ti with nanotopography was reduced by obtustatin, a α1β1 integrin inhibitor …”

Local release of magnesium from mesoporous TiO 2 coatings stimulates the peri-implant expression of osteogenic markers and improves osteoconductivity in vivo

“…Osteogenic cells and proteins of the extracellular matrix can interact with nano-sized surface features, triggering biological pathways for faster bone healing [2][3][4][5]. Intriguingly, most of the commercially available implants possess randomized nano-sized surface features, normally formed spontaneously by the oxidation of titanium in air [6].…”