Favorable manipulation of macrophage/endothelial cell functionality and their cross-talk on silicon-doped titania nanotube arrays

Abstract

Inflammatory reactions and the functionality of endothelial cells (ECs) on the surfaces of coronary stents are critical in the prevention of in-stent restenosis and subsequent neoatherosclerosis. However, the interactions between immune cells and ECs on modified coronary stent surfaces have long been underestimated. In the present study, silicon (Si)-doped titania nanotube arrays (TNA-Sis) were obtained via the facile anodization of magnetron-sputtered Ti–Si coatings. The synergetic effects of titania nanotube arrays (TNAs) and chemical cues (Si) on the functionality of macrophages (MΦs)/ECs and their cross-talk were investigated. The results indicated that TNA-Sis specimens, in comparison with TNAs alone, not only promoted the initial vitality of ECs, enhanced the expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO), and activated multiple cell signaling pathways (vWF, PECAM, eNOS), but also induced a favorable immune response through the polarization of MΦs to a pro-healing M2 phenotype via the activation of cell autophagy, resulting in the downregulation of inflammatory reactions. This beneficial immune response further facilitated cross-talk between ECs and MΦs, resulting in profoundly increased functionality of ECs on TNA-Sis surfaces. This study demonstrated that using TNA-Sis surface coatings for coronary stents may be a promising strategy to prevent in-stent restenosis.