Bone tissue engineering strategy based on the synergistic effects of silicon and strontium ions.

Multipotent human bone marrow mesenchymal stem cells (hBMSCs) are commonly used as seed cells in bone tissue engineering, but their clinical application is limited due to two challenges. One is the expansion of hBMSCs without loss of the stemness, and the other is the stimulation of osteogenic differentiation of hBMSCs when combined with biomaterials. In this study we demonstrated an approach by firstly elucidating the functional effects and optimal concentrations of Si and Sr ions on the proliferation and osteogenic differentiation of hBMSCs, and then designing bioactive bioceramic/alginate hydrogels which could release Si and Sr bioactive ions in the same optimal concentrations range for activation of the cells in vivo. The results showed that Si and Sr ions could synergistically stimulate cell proliferation without losing the stemness. Furthermore, at higher concentrations, Si and Sr ions stimulated osteogenic differentiation instead of enhancing proliferation. The designed bioactive hydrogels revealed activity to stimulate not only the osteogenic differentiation of encapsulated hBMSCs, but also the blood vessel formation in vivo. These results suggested that the design of biomaterials based on the biological function of different material elements was an effective approach for bone tissue engineering applications. STATEMENT OF SIGNIFICANCE: The clinical application of multipotent human bone marrow mesenchymal stem cells (hBMSCs) in bone tissue engineering is limited due to two challenges. One is the expansion of cells without loss of the stemness, and the other is the stimulation of osteogenic differentiation of hBMSCs within the biomaterial scaffolds. Herein, we demonstrated an approach by firstly elucidating the functional effects and optimal concentrations of Si and Sr ions on the proliferation without losing stemness and osteogenic differentiation of hBMSCs, and then designing a bioactive bioceramic/alginate hydrogel which could release Si and Sr ions for in vivo activation of cells. The bioactive hydrogels revealed activity to stimulate not only osteogenic differentiation of encapsulated hBMSCs, but also the blood vessel formation in vivo. Our work provided an effective approach to design effective biomaterials for tissue engineering.