3D-plotted zinc silicate/β-tricalcium phosphate ceramic scaffolds enable fast osteogenesis by activating the p38 signaling pathway

Abstract

Biomaterials in combination with multiple bioactive ions could create a favorable microenvironment for bone remolding. Herein, zinc silicate/β-tricalcium phosphate (ZS/β-TCP) composite ceramic scaffolds with different amounts of ZS (5, 10, and 15 wt%) were constructed using a three-dimensional fiber deposition (3DF) technique. The physicochemical, osteogenic and angiogenic properties of these interconnected macroporous scaffolds were investigated systematically. Simultaneously, GeneChip, alkaline phosphatase (ALP), western blot (WB) and polymerase chain reaction (PCR) were utilized to elucidate the underlying mechanism of the enhancement in osteogenic differentiation. The results showed that the incorporation of ZS significantly improved the mechanical performance by more than 5 fold in comparison with the β-TCP ceramic scaffold (4.79 ± 0.99 MPa). The ZS modified β-TCP scaffolds greatly supported the cytoactivity, adhesion, proliferation of mouse bone marrow mesenchymal stem cells (mBMSCs) and human umbilical vein endothelial cells (HUVECs). The expression levels of osteogenic genes and proteins as well as angiogenic genes were markedly upregulated by the sustained release of bioactive ions (mainly Si and Zn) from the composite scaffolds. The 10ZS/β-TCP demonstrated the best overall performance in vitro. Moreover, the 10ZS/β-TCP displayed a high bone volume fraction, bone maturity and angiogenesis after implantation in the rat skull defects for 6 weeks. It was further verified that ZS/β-TCP scaffolds stimulated the osteogenic differentiation of mBMSCs by activating the p38 signaling pathway directly. The 10ZS/β-TCP ceramic scaffold holds great potential for the fast repair of bone defects, and deep understanding of the mechanism will facilitate the formulation of new strategies for bone repair.