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

The immune reaction towards nanomaterials has long been concerned for the safety issue. A con-cept “nanoimmunotoxicity” was generated accordingly to describe this deleterious immunomodulatoryeffects. In additional to the detrimental effects, immune response has also been proved to be an essentialcomponent of the biomaterials-mediated reconstruction of a functional tissue. In this study, we inves-tigate the immunomodualtory effects of mesoporous silica nanoparticles (MSNs) on macrophages andthe effects of the generated osteoimmune environment on bone marrow mesenchymal stromal cells. Itis found that macrophages could uptake MSNs and elicited significant effects on inhibiting the inflam-matory response, which could be due to the inhibition of Wnt5A/Ca2+pathway and the activation ofautophagy. Interestingly, the modulated immune environment enhanced the osteogenic differentiationof bone marrow mesenchymal stromal cells, leading to the increase of mineralized nodules and alka-line phosphatase activity. This suggests that the immunomodulatory effects of nanomaterials are notalways 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 beshifted from “inert” to “immunomoluatory” to modulate an immune environment favourable for tissueregeneration and therapy.