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Open AccessArticle

Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis

Faculty of Dentistry, National University of Singapore, 9 Lower Kent Ridge Road, Singapore 119085, Singapore
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, IE Kent Ridge Road, Singapore 119228, Singapore
BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, MD6, 14 medical Drive, #14-01, Singapore 117599, Singapore
Department of Materials Science and Engineering, National University of Singapore, Blk EA, #03-09 9 Engineering Drive 1, Singapore 117575, Singapore
Centre for Advanced 2D Materials and Graphene Research Centre, National University of Singapore, 6 Science Drive 2, Singapore 117546, Singapore
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 574;
Received: 14 December 2018 / Revised: 22 January 2019 / Accepted: 23 January 2019 / Published: 29 January 2019
(This article belongs to the Special Issue Molecular Research on Dental Materials and Biomaterials 2018)
Graphene is capable of promoting osteogenesis without chemical induction. Nevertheless, the underlying mechanism(s) remain largely unknown. The objectives here were: (i) to assess whether graphene scaffolds are capable of supporting osteogenesis in vivo and; (ii) to ascertain the participation of the integrin/FAK mechanotransduction axis during the osteogenic differentiation induced by graphene. MSC-impregnated graphene scaffolds (n = 6) were implanted into immunocompromised mice (28 days). Alternatively, MSCs were seeded onto PDMS substrates (modulus of elasticity = 130, 830 and 1300 kPa) coated with a single monomolecular layer of graphene and cultured in basal medium (10 days). The ensuing expressions of FAK-p397, integrin, ROCK1, F-actin, Smad p1/5, RUNX2, OCN and OPN were evaluated by Western blot (n = 3). As controls, MSCs were plated onto uncoated PDMS in the presence of mechanotransduction inhibitors (echistatin, Y27632 and DMH1). MSC-impregnated graphene scaffolds exhibited positive immunoexpression of bone-related markers (RUNX2 and OPN) without the assistance of osteogenic inducers. In vitro, regardless of the stiffness of the underlying PDMS substrate, MSCs seeded onto graphene-coated PDMS substrates demonstrated higher expressions of all tested osteogenic and integrin/FAK proteins tested compared to MSCs seeded onto PDMS alone. Hence, graphene promotes osteogenesis via the activation of the mechanosensitive integrin/FAK axis. View Full-Text
Keywords: tissue engineering; differentiation; focal adhesion kinase; bone; nanomaterials; osteoblast; mechanical tissue engineering; differentiation; focal adhesion kinase; bone; nanomaterials; osteoblast; mechanical
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MDPI and ACS Style

Xie, H.; Cao, T.; Franco-Obregón, A.; Rosa, V. Graphene-Induced Osteogenic Differentiation Is Mediated by the Integrin/FAK Axis. Int. J. Mol. Sci. 2019, 20, 574.

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