<p>The Role of Autophagy in M2 Polarization of Macrophages Induced by Micro/Nano Topography</p>

Background: The proper topography of implant surface can induce macrophages polarization, whereas the regulation mechanism has not been fully deciphered. The study aimed to examine the regulation mechanism of macrophages M2 polarization by titanium (Ti) implant surface micro/nano topography. Results: Firstly, the titanium implant micropits-nanotubular surface with ∼ 30 nm diameters (MNT) can induce the M2 polarization of RAW264.7 spontaneously, as indicated by the spindle-like cell morphological alteration and specific molecular marker arginase-1 (Arg1) expression. Next, the autophagic vacuoles (AVs) number is significantly increased on MNT surface, as confirmed by the monodansylcadaverine (MDC) and CYTO-ID staining as well as the transmission electron microscope (TEM) observation. In addition, increasing or decreasing the autophagosomes number by rapamycin or 3-methyladenine (3-MA) will result in augmentation or attenuation of Arg1. Furthermore, blocking the fusion between autophagosomes and lysosomes by bafilomycin also significantly reduces Arg1, even in the presence of rapamycin. Finally, the ERK phosphorylation is selectively upregulated on MNT surface and the AVs number and Arg1 expression are significantly suppressed by U0126 treatment. Conclusion: Our findings suggest that the ERK-Beclin-1-autophagy axis may play a pivotal role in the regulation of M2 polarization induced by nanotopography. Keywords: macrophages polarization, micro/nano topography, TiO2 nanotubes, autophagy, ERK