title: Silicate bioceramics induce angiogenesis during bone regeneration.
abstract: The capacity to induce rapid vascular ingrowth during new bone formation is an important feature of biomaterials that are to be used for bone regeneration. Akermanite, a Ca-, Mg- and Si-containing bioceramic, has been demonstrated to be osteoinductive and to promote bone repair. This study further demonstrates the ability of akermanite to promote angiogenesis and investigates the mechanism of this behavior. The akermanite ion extract predominantly caused Si-ion-stimulated proliferation of human aortic endothelial cells. The Si ion in the extract was the most important component for the effect and the most effective concentration was found to be 0.6-2 μg ml(-1). In this range of Si ion concentration, the stimulating effect of the ceramic ion extract was demonstrated by the morphology of cells at the primary, interim and late stages during in vitro angiogenesis using ECMatrix™. The akermanite ion extract up-regulated the expression of genes encoding the receptors of proangiogenic cytokines and also increased the expression level of genes encoding the proangiogenic downstream cytokines, such as nitric oxide synthase and nitric oxide synthesis. Akermanite implanted in rabbit femoral condyle model promoted neovascularization after 8 and 16 weeks of implantation, which further confirmed its stimulation effect on angiogenesis in vivo. These results indicate that akermanite ceramic, an appropriate Si ion concentration source, could induce angiogenesis through increasing gene expression of proangiogenic cytokine receptors and up-regulated downstream signaling. To our knowledge, akermanite ceramic is the first Si-containing ceramic demonstrated to be capable of inducing angiogenesis during bone regeneration.
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Wanyin
authors.initials: W
authors.lastname: Zhai
authors.forename: Hongxu
authors.initials: H
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Lin
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Kerong
authors.initials: K
authors.lastname: Dai
authors.forename: Kawazoe
authors.initials: K
authors.lastname: Naoki
authors.forename: Guoping
authors.initials: G
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002130:Calcium Phosphates / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002516:Ceramics / Q000737:chemistry / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007477:Ions / Q000737:chemistry; D008422:Materials Testing; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D017640:Silicates / Q000737:chemistry / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D002130:Calcium Phosphates; D007477:Ions; D017640:Silicates; C023506:Glass ceramics; C018392:tricalcium phosphate