2025, Vol. 29 ›› Issue (28): 5941-5949

In vitro angiogenesis and osteogenesis properties of copper-doped mesoporous bioactive glass

Zeng Yu1, 2, Xie Chengwei3, Hong Yuanqi2, 4, Su Shenghui2, Dong Xieping2   

Abstract: BACKGROUND: Mesoporous bioactive glass has great application potential in bone repair due to its excellent biocompatibility and osteoinductive activity. Incorporating therapeutic ions into mesoporous bioactive glass particles can give the material more ideal biological properties.
OBJECTIVE: To synthesize copper-doped mesoporous bioactive glass and investigate its in vitro angiogenesis and osteogenic differentiation properties.
METHODS: Mesoporous bioactive glass and copper-doped mesoporous bioactive glass were synthesized by microemulsion-assisted sol-gel method. The morphology, structure, composition, and ion release performance of the materials were characterized by scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, and X-ray diffraction. The extracts of mesoporous bioactive glass and copper-doped mesoporous bioactive glass were co-cultured with mouse fibroblasts L929. Biocompatibility of the materials was evaluated by live/dead staining and CCK-8 assay. The extracts of the two materials were co-cultured with human umbilical vein endothelial cells. The angiogenesis-promoting properties of the materials were evaluated by Transwell assay, scratch assay, and CD31 immunofluorescence staining. The extracts of the two materials were co-cultured with mouse bone marrow mesenchymal stem cells. The osteogenic properties of the materials were evaluated by alkaline phosphatase staining (without osteogenic induction solution) and Alizarin red staining (with osteogenic induction solution).
RESULTS AND CONCLUSION: (1) The characterization results exhibited that both mesoporous bioactive glass and copper-doped mesoporous bioactive glass presented a tightly packed granular morphology with similar internal mesoporous structures, and copper-doped mesoporous bioactive glass could continuously release copper ions. (2) The live/dead staining and CCK-8 assay results showed that compared with mesoporous bioactive glass, copper-doped mesoporous bioactive glass could promote the proliferation of L929 cells and had good biocompatibility. (3) The results of Transwell assay, scratch assay, and CD31 immunofluorescence staining exhibited that compared with mesoporous bioactive glass, copper-doped mesoporous bioactive glass could promote the migration of human umbilical vein endothelial cells and the expression of CD31 protein, and promote angiogenesis. (4) The results of alkaline phosphatase staining and alizarin red staining demonstrated that the osteogenic performance of copper-doped mesoporous bioactive glass was stronger than that of mesoporous bioactive glass. The results indicate that copper-doped mesoporous bioactive glass has excellent biocompatibility and the potential to promote angiogenesis and bone regeneration.

Key words: mesoporous bioactive glass, copper, angiogenesis, osteogenesis, inorganic growth factor, tissue engineering, biomaterial, bioactivity, engineered bone material