title: Graphene Oxide-Copper Nanocomposite-Coated Porous CaP Scaffold for Vascularized Bone Regeneration via Activation of Hif-1α.
abstract: Graphene has been studied for its in vitro osteoinductive capacity. However, the in vivo bone repair effects of graphene-based scaffolds remain unknown. The aqueous soluble graphene oxide-copper nanocomposites (GO-Cu) are fabricated, which are used to coat porous calcium phosphate (CaP) scaffolds for vascularized bone regeneration. The GO-Cu nanocomposites, containing crystallized CuO/Cu2 O nanoparticles of ≈30 nm diameters, distribute uniformly on the surfaces of the porous scaffolds and maintain a long-term release of Cu ions. In vitro, the GO-Cu coating enhances the adhesion and osteogenic differentiation of rat bone marrow stem cells (BMSCs). It is also found that by activating the Erk1/2 signaling pathway, the GO-Cu nanocomposites upregulate the expression of Hif-1α in BMSCs, resulting in the secretion of VEGF and BMP-2 proteins. When transplanted into rat with critical-sized calvarial defects, the GO-Cu-coated calcium phosphate cement (CPC) scaffolds (CPC/GO-Cu) significantly promote angiogenesis and osteogenesis. Moreover, it is observed via histological sections that the GO-Cu nanocomposites are phagocytosed by multinucleated giant cells. The results suggest that GO-Cu nanocomposite coatings can be utilized as an attractive strategy for vascularized bone regeneration.
authors.affiliation: Department of Prosthodontics, Oral Bioengineering and regenerative medicine Lab, Ninth People's Hospital affiliated to Shanghai Jiao, Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Clinical Research Center, Shanghai Jiading Central Hospital, 1 Chengbei Road, Shanghai, 201800, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Department of Prosthodontics, Oral Bioengineering and regenerative medicine Lab, Ninth People's Hospital affiliated to Shanghai Jiao, Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Prosthodontics, Oral Bioengineering and regenerative medicine Lab, Ninth People's Hospital affiliated to Shanghai Jiao, Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Guanglong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Prosthodontics, Oral Bioengineering and regenerative medicine Lab, Ninth People's Hospital affiliated to Shanghai Jiao, Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Guangzheng
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Prosthodontics, Oral Bioengineering and regenerative medicine Lab, Ninth People's Hospital affiliated to Shanghai Jiao, Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Xiansong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Bio-Nano Science and Engineering, Key Laboratory for Thin Film and Microfabrication of Ministryof Education, Research Institute of Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Prosthodontics, Oral Bioengineering and regenerative medicine Lab, Ninth People's Hospital affiliated to Shanghai Jiao, Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000737:chemistry / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000737:chemistry*; D006108:Graphite / Q000737:chemistry*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D053761:Nanocomposites; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000502:physiology; D010087:Oxides / Q000737:chemistry*; D016062:Porosity; D051381:Rats; D011916:Rats, Inbred F344; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D001843:Bone Cements; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010087:Oxides; D006108:Graphite; D003300:Copper; C020243:calcium phosphate
keywords: Hif-1α; bone regeneration; copper nanocomposites; graphene oxides; vascularization