Thermoresponsive Citrate-Based Graphene Oxide Scaffold Enhances Bone Regeneration from BMP9-Stimulated Adipose-Derived Mesenchymal Stem Cells

Chen Zhao, Zongyue Zeng, Nader Taheri Qazvini, Xinyi Yu, Ruyi Zhang, Shujuan Yan, Yi Shu, Yunxiao Zhu, Chongwen Duan, Elliot Bishop, Jiayan Lei, Wenwen Zhang, Chao Yang, Ke Wu, Ying Wu, Liping An, Shifeng Huang, Xiaojuan Ji, Cheng Gong, Chengfu YuanLinghuan Zhang, Wei Liu, Bo Huang, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Xi Wang, Wenping Luo, Leonardo Oliveira, Aravind Athiviraham, Michael J. Lee, Jennifer Moriatis Wolf, Guillermo A. Ameer, Russell R. Reid, Tong Chuan He*, Wei Huang

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

54 Scopus citations


Effective bone tissue engineering is important to overcome the unmet clinical challenges as more than 1.6 million bone grafts are done annually in the United States. Successful bone tissue engineering needs minimally three critical constituents: osteoprogenitor cells, osteogenic factors, and osteoinductive/osteoconductive scaffolds. Osteogenic progenitors are derived from multipotent mesenchymal stem cells (MSCs), which can be prepared from numerous tissue sources, including adipose tissue. We previously showed that BMP9 is the most osteogenic BMP and induces robust bone formation of immortalized mouse adipose-derived MSCs entrapped in a citrate-based thermoresponsive hydrogel referred to as PPCNg. As graphene and its derivatives emerge as promising biomaterials, here we develop a novel thermosensitive and injectable hybrid material by combining graphene oxide (GO) with PPCNg (designated as GO-P) and characterize its ability to promote bone formation. We demonstrate that the thermoresponsive behavior of the hybrid material is maintained while effectively supporting MSC survival and proliferation. Furthermore, GO-P induces early bone-forming marker alkaline phosphatase (ALP) and potentiates BMP9-induced expression of osteogenic regulators and bone markers as well as angiogenic factor VEGF in MSCs. In vivo studies show BMP9-transduced MSCs entrapped in the GO-P scaffold form well-mineralized and highly vascularized trabecular bone. Thus, these results indicate that GO-P hybrid material may function as a new biocompatible, injectable scaffold with osteoinductive and osteoconductive activities for bone regeneration.

Original languageEnglish (US)
Pages (from-to)2943-2955
Number of pages13
JournalACS Biomaterials Science and Engineering
Issue number8
StatePublished - Aug 13 2018


  • BMP9
  • PPCN
  • bone tissue engineering
  • graphene
  • graphene oxide
  • mesenchymal stem cells
  • scaffold
  • thermoresponsive

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials


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