The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis.

As a newly discovered substrate anchored extracellular vesicles, migrasomes (Migs) may bring a new opportunity for manipulating target cells bioactivities. In this study, the M2 macrophages derived Migs were obtained by titania nanotubes surface (NTs). Due to the benefits of nanostructured, the NTs surface was not only able to induce RAW264.7 for M2 polarization, but also generated more Migs formation, which could be internalized by following seeded mesenchymal stem cells (MSCs). Then the NTs surface induced Migs were collected by density-gradient centrifugation for MSCs treatment. As indicated by immunofluorescence staining, alkaline phosphatase activity and alizarin red staining, the osteogenic differentiation capacity of MSCs was significantly enhanced by Migs treatment, in line with the dosage. By RNA-sequence analysis, the enhancement of osteogenic differentiation was correlated with PI3K-AKT pathway activation that might be originated from the M2 polarization state of donor cells. Finally, the Migs were coated onto Ti surface for therapeutic application. Both the in vitro and in vivo analysis revealed that the Migs coated Ti implant showed significant enhancement of osteogenesis. In conclusion, this study suggests that the nanosurface may be a favorable platform for Migs production, which may bring a new concept for tissue regeneration. This article is protected by copyright. All rights reserved.