Immunomodulatory effects of mesoporous silica nanoparticles on osteogenesis: From nanoimmunotoxicity to nanoimmunotherapy

Abstract

The immune reaction towards nanomaterials has long been concerned for the safety issue. A concept “nanoimmunotoxicity” was generated accordingly to describe this deleterious immunomodulatory effects. In additional to the detrimental effects, immune response has also been proved to be an essential component of the biomaterials-mediated reconstruction of a functional tissue. In this study, we investigate the immunomodualtory effects of mesoporous silica nanoparticles (MSNs) on macrophages and the effects of the generated osteoimmune environment on bone marrow mesenchymal stromal cells. It is found that macrophages could uptake MSNs and elicited significant effects on inhibiting the inflammatory response, which could be due to the inhibition of Wnt5A/Ca2+ pathway and the activation of autophagy. Interestingly, the modulated immune environment enhanced the osteogenic differentiation of bone marrow mesenchymal stromal cells, leading to the increase of mineralized nodules and alkaline phosphatase activity. This suggests that the immunomodulatory effects of nanomaterials are not always detrimental, but can be beneficial for tissue regeneration. In addition to the detrimental effects, the positive effects of nanomaterial-mediated immune response should be emphasized. The concept “nanoimmumotherpy” was proposed accordingly, and the paradigm on design nanomaterials should be shifted from “inert” to “immunomoluatory” to modulate an immune environment favourable for tissue regeneration and therapy.