posted on 2018-06-07, 00:00authored byChen 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 Yuan, Linghuan 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
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.