@article{38ce03afc08547d2bf6ee3c8940954a0,
title = "Thermoresponsive Citrate-Based Graphene Oxide Scaffold Enhances Bone Regeneration from BMP9-Stimulated Adipose-Derived Mesenchymal Stem Cells",
abstract = "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.",
keywords = "BMP9, PPCN, bone tissue engineering, graphene, graphene oxide, mesenchymal stem cells, scaffold, thermoresponsive",
author = "Chen Zhao and Zongyue Zeng and Qazvini, {Nader Taheri} and Xinyi Yu and Ruyi Zhang and Shujuan Yan and Yi Shu and Yunxiao Zhu and Chongwen Duan and Elliot Bishop and Jiayan Lei and Wenwen Zhang and Chao Yang and Ke Wu and Ying Wu and Liping An and Shifeng Huang and Xiaojuan Ji and Cheng Gong and Chengfu Yuan and Linghuan Zhang and Wei Liu and Bo Huang and Yixiao Feng and Bo Zhang and Zhengyu Dai and Yi Shen and Xi Wang and Wenping Luo and Leonardo Oliveira and Aravind Athiviraham and Lee, {Michael J.} and Wolf, {Jennifer Moriatis} and Ameer, {Guillermo A.} and Reid, {Russell R.} and He, {Tong Chuan} and Wei Huang",
note = "Funding Information: The reported work was supported in part by research grants from the National Institutes of Health (Grants CA226303 and DE020140 to T.C.H. and R.R.R.), the U.S. Department of Defense (Grant OR130096 to J.M.W.), the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust (R.R.R., T.C.H., and G.A.A.), the Scoliosis Research Society (T.C.H. and M.J.L.), the NIST CHiMAD (Grant 70NANB14H012 to N.T.Q.), the National Key Research and Development Program of China (Grants 2016YFC1000803 and 2011CB707906 to T.C.H.), and the National Natural Science Foundation of China (Grants 81371972 and 81572142 to W.H.). Z.Z., R.Z., Y.S., Y.W., W.Z., L.A., C.Y., B.H., Y.F., and B.Z. received scholarship funding from the China Scholarship Council. This project was also supported in part by The University of Chicago Cancer Center Support Grant (P30CA014599) and the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430. In addition, the reported work utilized The University of Chicago{\textquoteright}s MRSEC Facilities, which are supported by the National Science Foundation (Grant NSF-DMR-1420709).",
year = "2018",
month = aug,
day = "13",
doi = "10.1021/acsbiomaterials.8b00179",
language = "English (US)",
volume = "4",
pages = "2943--2955",
journal = "ACS Biomaterial Science and Engineering",
issn = "2373-9878",
publisher = "American Chemical Society",
number = "8",
}