title: Copper-doped borosilicate bioactive glass scaffolds with improved angiogenic and osteogenic capacity for repairing osseous defects.
abstract: There is growing interest in the use of synthetic biomaterials to deliver inorganic ions that are known to stimulate angiogenesis and osteogenesis in vivo. In the present study, we investigated the effects of varying amounts of copper in a bioactive glass on the response of human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro and on blood vessel formation and bone regeneration in rat calvarial defects in vivo. Porous scaffolds of a borosilicate bioactive glass (composition 6Na2O, 8K2O, 8MgO, 22CaO, 36B2O3, 18SiO2, 2P2O5, mol.%) doped with 0.5, 1.0 and 3.0wt.% CuO were created using a foam replication method. When immersed in simulated body fluid, the scaffolds released Cu ions into the medium and converted to hydroxyapatite. At the concentrations used, the Cu in the glass was not toxic to the hBMSCs cultured on the scaffolds in vitro. The alkaline phosphatase activity of the hBMSCs and the expression levels of angiogenic-related genes (vascular endothelial growth factor and basic fibroblast growth factor) and osteogenic-related genes (runt-related transcription factor 2, bone morphogenetic protein-2 and osteopontin) increased significantly with increasing amount of Cu in the glass. When implanted in rat calvarial defects in vivo, the scaffolds (3wt.% CuO) significantly enhanced both blood vessel formation and bone regeneration in the defects at 8weeks post-implantation. These results show that doping bioactive glass implants with Cu is a promising approach for enhancing angiogenesis and osteogenesis in the healing of osseous defects.
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, People's Republic of China.
authors.forename: Shichang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, People's Republic of China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China.
authors.forename: Wenhai
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Materials Science and Engineering, and Center for Biomedical Science and Engineering, Missouri University of Science and Technology, Rolla, MO 65409-0340, USA.
authors.forename: Mohamed N
authors.initials: MN
authors.lastname: Rahaman
authors.affiliation: Department of Orthopaedics, Shanghai Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Zhongtang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Materials Science and Engineering, Tongji University, Shanghai 200092, People's Republic of China. Electronic address: wdpshk@tongji.edu.cn.
authors.forename: Deping
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, People's Republic of China. Electronic address: shzhangchangqing@163.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001826:Body Fluids / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology*; D017886:Durapatite / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005898:Glass; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011859:Radiography; D017207:Rats, Sprague-Dawley; D017640:Silicates / Q000494:pharmacology*; D012886:Skull / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017640:Silicates; D015675:Osteocalcin; D003300:Copper; D017886:Durapatite; D000469:Alkaline Phosphatase
keywords: Angiogenesis; Copper-doped bioactive glass; Osteogenesis; Scaffold; Stem cells