Gelatin-Derived Graphene-Silicate Hybrid Materials Are Biocompatible and Synergistically Promote BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

Yulong Zou, Nader Taheri Qazvini, Kylie Zane, Monirosadat Sadati, Qiang Wei, Junyi Liao, Jiaming Fan, Dongzhe Song, Jianxiang Liu, Chao Ma, Xiangyang Qu, Liqun Chen, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye WuYi Shu, Yasha Li, Wenwen Zhang, Russell R. Reid, Michael J. Lee, Jennifer Moritis Wolf, Matthew Tirrell, Tong Chuan He, Juan J. De Pablo, Zhong Liang Deng

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Graphene-based materials are used in many fields but have found only limited applications in biomedicine, including bone tissue engineering. Here, we demonstrate that novel hybrid materials consisting of gelatin-derived graphene and silicate nanosheets of Laponite (GL) are biocompatible and promote osteogenic differentiation of mesenchymal stem cells (MSCs). Homogeneous cell attachment, long-term proliferation, and osteogenic differentiation of MSCs on a GL-scaffold were confirmed using optical microscopy and scanning electron microscopy. GL-powders made by pulverizing the GL-scaffold were shown to promote bone morphogenetic protein (BMP9)-induced osteogenic differentiation. GL-powders increased the alkaline phosphatase (ALP) activity in immortalized mouse embryonic fibroblasts but decreased the ALP activity in more-differentiated immortalized mouse adipose-derived cells. Note, however, that GL-powders promoted BMP9-induced calcium mineral deposits in both MSC lines, as assessed using qualitative and quantitative alizarin red assays. Furthermore, the expression of chondro-osteogenic regulator markers such as Runx2, Sox9, osteopontin, and osteocalcin was upregulated by the GL-powder, independent of BMP9 stimulation; although the powder synergistically upregulated the BMP9-induced Osterix expression, the adipogenic marker PPARγ was unaffected. Furthermore, in vivo stem cell implantation experiments demonstrated that GL-powder could significantly enhance the BMP9-induced ectopic bone formation from MSCs. Collectively, our results strongly suggest that the GL hybrid materials promote BMP9-induced osteogenic differentiation of MSCs and hold promise for the development of bone tissue engineering platforms.

Original languageEnglish (US)
Pages (from-to)15922-15932
Number of pages11
JournalACS Applied Materials and Interfaces
Volume9
Issue number19
DOIs
StatePublished - May 17 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.

Keywords

  • Laponite
  • bone morphogenetic protein
  • bone tissue engineering
  • graphene
  • mesenchymal stem cells

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