Biomaterials with excellent osteogenic and angiogenic activities are desirable to repair massive bone defects. Decellularized matrix from porcine small intestinal submucosa (SIS) has attracted particular attention for tissue regeneration because it has strong angiogenic effects and retains plentiful bioactive components. However, it has inferior osteoinductivity and osteoconductivity. In this study, we developed porous composite of SIS combined with mesoporous bioactive glass (SIS/MBG) with the goal of improving the mechanical and biological properties. SIS/MBG scaffolds showed uniform interconnected macropores ~150 µm), high porosity (~76%), and enhanced compressive strength (~0.87 MPa). The proliferation and osteogenic gene expression (Runx2, ALP, Ocn, and Col-Iα) of rat bone marrow stromal cells (rBMSCs) as well as the proliferation, angiogenic gene expression (VEGF, bFGF, and KDR), and tube formation capacity of human umbilical vein endothelial cells (HUVECs) in SIS/MBG scaffolds were significantly upregulated compared with nonmesoporous bioactive glass (BG)-modified SIS (SIS/BG) and SIS-only scaffolds. Western blot analysis revealed that SIS/MBG induced rBMSCs to osteogenic differentiation through the activation of Wnt/ß-Catenin signaling pathway, and SIS/MBG enhanced angiogenic activity of HUVEC through the activation of PI3k/Akt pathways. The in vivo results demonstrated that SIS/MBG scaffolds significantly enhanced new bone formation and neovascularization simultaneously in critical-sized rat calvarial defects as compared with SIS/BG and SIS. Collectively, the osteostimulative and angiostimulative biomimetic composite scaffold SIS/MBG represents an exciting biomaterial option for bone regeneration.
- angiogenesis,
- mesoporous bioactive glass,
- osteogenesis,
- signal pathways,
- small intestinal submucosa
Available at: http://works.bepress.com/hu-yang/84/
This work was financially supported by the National Natural Science Foundation of China (Grant No. 81672158 and 81371939), International Science & Technology Co-operation Program of China (2013DFG32690), and National Key R&D Program of China (2016YFC1100100).