title: Stimulation of osteogenesis and angiogenesis of hBMSCs by delivering Si ions and functional drug from mesoporous silica nanospheres.
abstract: Multifunctional bioactive materials with the ability to stimulate osteogenesis and angiogenesis of stem cells play an important role in the regeneration of bone defects. However, how to develop such biomaterials remains a significant challenge. In this study, we prepared mesoporous silica nanospheres (MSNs) with uniform sphere size (∼90 nm) and mesopores (∼2.7 nm), which could release silicon ions (Si) to stimulate the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) via activating their ALP activity, bone-related gene and protein (OCN, RUNX2 and OPN) expression. Hypoxia-inducing therapeutic drug, dimethyloxaloylglycine (DMOG), was effectively loaded in the mesopores of MSNs (D-MSNs). The sustained release of DMOG from D-MSNs could stabilize HIF-1α and further stimulated the angiogenic differentiation of hBMSCs as indicated by the enhanced VEGF secretion and protein expression. Our study revealed that D-MSNs could combine the stimulatory effect on both osteogenic and angiogenic activity of hBMSCs. The potential mechanism of D-MSN-stimulated osteogenesis and angiogenesis was further elucidated by the supplementation of cell culture medium with pure Si ions and DMOG. Considering the easy handling characteristics of nanospheres, the prepared D-MSNs may be applied in the forms of injectable spheres for minimally invasive surgery, or MSNs/polymer composite scaffolds for bone defect repair. The concept of delivering both stimulatory ions and functional drugs may offer a new strategy to construct a multifunctional biomaterial system for bone tissue regeneration.
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Shi
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Jin
authors.initials: J
authors.lastname: Shao
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Zetao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China.
authors.forename: Botao
authors.initials: B
authors.lastname: Song
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China. Electronic address: jchang@mail.sic.ac.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.affiliation: State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People's Republic of China. Electronic address: chengtiewu@mail.sic.ac.cn.
authors.forename: Chengtie
authors.initials: C
authors.lastname: Wu
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, 60 Musk Ave, Kelvin Grove, Brisbane, Queensland 4059, Australia.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008854:Microscopy, Electron; D049329:Nanostructures; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D012822:Silicon Dioxide
keywords: Angiogenesis; Bone regeneration; Mesoporous silica nanospheres; Multifunction; Osteogenesis