Nano-Roughness-Mediated Macrophage Polarization for Desired Host Immune Response

Abstract

Macrophage polarization is a significant event in the host immune response, which can be modulated by modifying the surface of a biomaterial. Previous studies have demonstrated the modulation of macrophage polarization using different surface features; however, none of these studies reflect the effect of surface properties on unstimulated macrophage polarization for a prolonged period. To better understand the impact of surface features, in this work differentiated THP-1 cells are employed to control macrophage polarization on nano-rough surfaces for a duration of 7 days. Model nano-rough substrates are fabricated by immobilizing gold nanoparticles (AuNPs) of predetermined sizes (16, 38, 68 nm) on a 2-methyl-2-oxazoline thin film, followed by tailoring the outermost surface chemistry. All modified surfaces support high levels of cell adhesion and proliferation. Over time, the expression of pro-inflammatory cytokines decreases, whereas the expression of anti-inflammatory cytokines increases on all modified surfaces. Similarly, pro-inflammatory interleukin (IL)-1β gene expression is downregulated, and anti-inflammatory IL-10-gene expression is upregulated, regardless of the surface roughness. Analysis of cell morphology reveals that the predominant cell type on the modified surfaces exhibits M2 anti-inflammatory phenotype. Herein, how surface features can modulate macrophage responses over an extended period is highlighted, offering insights for the development of future biomaterial implants.