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.