Unique regulation of TiO₂ nanoporous topography on macrophage polarization via MSC-derived exosomes

The comprehensive recognition of communications between bone marrow mesenchymal stem cells (bm-MSCs) and macrophages in the peri-implant microenvironment is crucial for implantation prognosis. Our previous studies have clarified the indirect influence of Ti surface topography in the osteogenic differentiation of bm-MSCs through modulating macrophage polarization. However, cell communication is commutative and multi-directional. As the immune regulatory properties of MSCs have become increasingly prominent, whether bm-MSCs could also play an immunomodulatory role on macrophages under the influence of Ti surface topography is unclear. To further illuminate the communications between bm-MSCs and macrophages, the bm-MSCs inoculated on Ti with nanoporous topography were indirectly co-cultured with macrophages, and by blocking exosome secretion or extracting the purified exosomes to induce independently, we bidirectionally confirmed that under the influence of TiO₂ nanoporous topography with 80-100 nm tube diameters, bm-MSCs can exert immunomodulatory effects through exosome-mediated paracrine actions and induce M1 polarization of macrophages, adversely affecting the osteogenic microenvironment around the implant. This finding provides a reference for the optimal design of the implant surface topography for inducing better bone regeneration.