Abstract
Insufficient nutrition exchange and limited transportation of blood supply in a porous only scaffold often hinder bone formation, even though the porous scaffold is loaded with cells or growth factors. To overcome these issues, we developed a cell- and growth factor-free approach to induce bone formation in a critical-size bone defect by using an interconnected porous beta-tricalcium phosphate (β-TCP) scaffold with multiple channels. In vitro cell experimental results showed that multiple channels significantly promoted cell attachment and proliferation of human bone marrow mesenchymal stem cells, stimulated their alkaline phosphatase activity, and up-regulated the osteogenic gene expression. Multiple channels also considerably stimulated the expression of various mechanosensing markers of the cells, such as focal adhesion kinase, filamentous actin, and Yes-associated protein-1 at both static and dynamic culturing conditions. The in vivo bone defect implantation results demonstrated more bone formation inside multiple-channeled scaffolds compared to non-channeled scaffolds. Multiple channels prominently accelerated collagen type I, bone sialoprotein and osteocalcin protein expression. Fluorochrome images and angiogenic marker CD31 staining exhibited more mineral deposition and longer vasculature structures in multiple-channeled scaffolds, compared to non-channeled scaffolds. All the findings suggested that the creation of interconnected multiple channels in the porous β-TCP scaffold is a very promising approach to promote bone tissue regeneration.
Highlights
Insufficient nutrition exchange and limited transportation of blood supply in a porous only scaffold often hinder bone formation, even though the porous scaffold is loaded with cells or growth factors
We found that multiple channels in a porous β-TCP scaffold promoted mandibular bone and vasculature formation in beagle dogs with the assistance of bone forming peptide-1 (BFP-1)[16]
According to the studies which displayed that shear stress plays an essential role in modulating mesenchymal stem cell osteogenic differentiation, collagen secretion, and matrix mineralization[18,19,20,21], in this study we hypothesize that the multiple channels created inside porous β-TCP scaffold can activate shear force-driven mechanotransduction of cells, which can effectively stimulate the attachment, proliferation, and differentiation of mesenchymal stem cells in vitro, and sustainably activate osteogenesis and bone mineralization mechanism in vivo
Summary
Insufficient nutrition exchange and limited transportation of blood supply in a porous only scaffold often hinder bone formation, even though the porous scaffold is loaded with cells or growth factors. Limited nutrient diffusion and transportation within the porous scaffold results in insufficient vascularization, low cell proliferation and survival rate, which in turn decreases bone formation and engraftment rate. These issues shadowed porous β-TCP scaffold’ ability in bone regeneration, and in repair of large craniofacial bone d efects[11,12,13,14,15]. Channel-pore geometry, which activated certain integrins to promote endothelial cell infiltration and migration[17] It is still unclear whether the interconnected multiple channels-pores architecture can induce osteogenic stem cell differentiation in vitro and promote vascularization and bone regeneration in vivo.
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