Abstract
In bone regeneration, there are some important cellular biological processes, such as mineralization, cell organization, and differentiation. In particular, vascularization into regenerative tissues is a key step for the survival of cells and tissues. In this study, to fabricate biomimetic-engineered bone, including vascular networks, we focused on connective tissue growth factor (CTGF), a multifunctional protein which could regulate the extracellular matrix remodeling. By combination with CTGF and hydroxyapatite (HAp) ceramics (2D) or apatite-fiber scaffold (AFS, 3D), we have fabricated bioactive materials. The CTGF-loaded HAp ceramics could enhance the cellular attachment through interaction with integrin and promote actin cytoskeletal reorganization. CTGF-loaded HAp also enhanced the differentiation of osteoblasts by integrin-mediated activation of the signaling pathway. Under co-culture conditions, both osteoblasts and endothelial cells in the CTGF-loaded AFS were stimulated by CTGF, and each cell could penetrate the central region of the scaffold in vitro and in vivo. Direct cell-cell interaction would also improve the functionality of cells in bone formation. These results suggest that coupling between effective optimized scaffold and CTGF with multifunction could provide better mimicking natural bone by stimulation of angiogenesis.
Highlights
In bone tissue engineering, it is desirable that the scaffold could induce the osteogenesis and angiogenesis for enhancement of cell proliferation, differentiation, and matrix formation
To develop engineered constructs with the enhancement of the vascular networks and bone formation, we focused on connective tissue growth factor (CTGF) and fabricated CTGF-loaded 2D or 3D bioactive materials
We evaluated the ability of angiogenesis by CTGF-loaded Apatite-fiber scaffolds (AFSs) in vivo
Summary
It is desirable that the scaffold could induce the osteogenesis and angiogenesis for enhancement of cell proliferation, differentiation, and matrix formation. In order to mimic native tissue environment, scaffolds with three-dimensional porous structure have been already fabricated by a variety of processes [1,2,3]. Bone is a highly vascularized tissue and has a dynamic remodeling system with complex construction. The highly vascularized tissue is dependent on the spatiotemporal relationship between blood vessels and osteoblastic cells. Vascular networks are indispensable to supply cells with nutrients and oxygen for engineered tissue including bone after implantation. The lack of blood supply will be a major obstacle in tissue regeneration. Cells should induce angiogenesis around the tissue, via the newly formed vessel to deliver the nutrients, to establish a blood supply and remove the metabolic wastes. Various strategies, such as cell kinetics by growth factor delivery, co-culturing systems, application
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