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

Abstract

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.

Integrating physicomechanical and biological strategies for BTE: biomaterials-induced osteogenic differentiation of MSCs

“…Furthermore, Wang et al discovered that the alteration in the diameter of micropatterned nanotubes also affected the polarization direction: macrophages on small diameter(30nm) nanotubes were more inclined to M2 polarization, and those on large diameter(100nm) nanotubes had the opposite results 281 . Similar conclusion was obtained by using Ti nanotubes with diameters of 80-100nm 290 . And by blocking the secretion of MSCs exosomes, it was concluded that M1 polarization was regulated by the paracrine pathway of MSCs.…”

Nano implant surface triggers autophagy through membrane curvature distortion to regulate the osteogenic differentiation

“…differentiation through autophagy. The nano surfaces with different dimensions have been prepared by anodization, which is a well-documented technique with excellent biocompatibility as previously reported [13,23]. From the proteomic analysis, autophagy was top enriched as KEGG enrichment analysis in the comparison between nano and smooth surfaces.…”

Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine

“…Conversely, another study demonstrated that the TiO 2 nanoporous topography promoted MSC-Exo to play an immunomodulatory role by inducing the M1 polarization of macrophages, potentially having a detrimental impact on the osteogenesis process. 157 Furthermore, the stiffness of the extracellular matrix (ECM) also mattered. Excessive ECM deposition in the tumour microenvironment may lead to an increase in substrate hardness, thereby promoting the secretion and modulating the biological behaviours of exosomes derived from cancer cells.…”