Silicate bioceramics enhanced vascularization and osteogenesis through stimulating interactions between endothelia cells and bone marrow stromal cells.
The facts that biomaterials affect the behavior of single type of cells have been widely accepted. However, the effects of biomaterials on cell-cell interactions have rarely been reported. Bone tissue engineering involves osteoblastic cells (OCs), endothelial cells (ECs) and the interactions between OCs and ECs. It has been reported that silicate biomaterials can stimulate osteogenic differentiation of OCs and vascularization of ECs. However, the effects of silicate biomaterials on the interactions between ECs and OCs during vascularization and osteogenesis have not been reported, which are critical for bone tissue regeneration in vivo. Therefore, this study aimed to investigate the effects of calcium silicate (CS) bioceramics on interactions between human umbilical vein endothelial cells (HUVECs) and human bone marrow stromal cells (HBMSCs) and on stimulation of vascularization and osteogenesis in vivo through combining co-cultures with CS containing scaffolds. Specifically, the effects of CS on the angiogenic growth factor VEGF, osteogenic growth factor BMP-2 and the cross-talks between VEGF and BMP-2 in the co-culture system were elucidated. Results showed that CS stimulated co-cultured HBMSCs (co-HBMSCs) to express VEGF and the VEGF activated its receptor KDR on co-cultured HUVECs (co-HUVECs), which was also up-regulated by CS. Then, BMP-2 and nitric oxide expression from the co-HUVECs were stimulated by CS and the former stimulated osteogenic differentiation of co-HBMSCs while the latter stimulated vascularization of co-HVUECs. Finally, the poly(lactic-co-glycolic acid)/CS composite scaffolds with the co-cultured HBMSCs and HUVECs significantly enhanced vascularization and osteogenic differentiation in vitro and in vivo, which indicates that it is a promising way to enhance bone regeneration by combining scaffolds containing silicate bioceramics and co-cultures of ECs and OCs.
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
Haiyan
H
Li
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.
Ke
K
Xue
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China.
Ni
N
Kong
Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China. Electronic address: drkailiu@126.com.
Kai
K
Liu
Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, China; Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai 200050, China. Electronic address: Jchang@mail.sic.ac.cn.
Jiang
J
Chang
D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2 / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002516:Ceramics; D018920:Coculture Techniques; D017931:DNA Primers; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D060888:Real-Time Polymerase Chain Reaction; D017640:Silicates / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D055396:Bone Morphogenetic Protein 2; D017931:DNA Primers; D017640:Silicates; D042461:Vascular Endothelial Growth Factor A
Bone tissue engineering; Osteogenesis; Silicate bioceramics; Vascularization