TY - JOUR
T1 - Gelatin-Derived Graphene-Silicate Hybrid Materials Are Biocompatible and Synergistically Promote BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells
AU - Zou, Yulong
AU - Qazvini, Nader Taheri
AU - Zane, Kylie
AU - Sadati, Monirosadat
AU - Wei, Qiang
AU - Liao, Junyi
AU - Fan, Jiaming
AU - Song, Dongzhe
AU - Liu, Jianxiang
AU - Ma, Chao
AU - Qu, Xiangyang
AU - Chen, Liqun
AU - Yu, Xinyi
AU - Zhang, Zhicai
AU - Zhao, Chen
AU - Zeng, Zongyue
AU - Zhang, Ruyi
AU - Yan, Shujuan
AU - Wu, Tingting
AU - Wu, Xingye
AU - Shu, Yi
AU - Li, Yasha
AU - Zhang, Wenwen
AU - Reid, Russell R.
AU - Lee, Michael J.
AU - Wolf, Jennifer Moritis
AU - Tirrell, Matthew
AU - He, Tong Chuan
AU - De Pablo, Juan J.
AU - Deng, Zhong Liang
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/5/17
Y1 - 2017/5/17
N2 - 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.
AB - 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.
KW - Laponite
KW - bone morphogenetic protein
KW - bone tissue engineering
KW - graphene
KW - mesenchymal stem cells
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UR - http://www.scopus.com/inward/citedby.url?scp=85019581743&partnerID=8YFLogxK
U2 - 10.1021/acsami.7b00272
DO - 10.1021/acsami.7b00272
M3 - Article
C2 - 28406027
AN - SCOPUS:85019581743
SN - 1944-8244
VL - 9
SP - 15922
EP - 15932
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 19
ER -