The effects of TiO₂ nanotube arrays with different diameters on macrophage/endothelial cell response and <i>ex vivo</i> hemocompatibility

Abstract

nanotube arrays (TNAs) with different diameters were fabricated by anodization. The diameter could be precisely adjusted from 15 nm (Nano-15) to 120 nm (Nano-120). The effect of distinct nanodimensions on the behavior of ECs/MΦs and their crosstalk was investigated. The results indicated that Nano-15 not only promoted the initial vitality of ECs and function-related gene expression but also enhanced the activation and spread of MΦs. In addition, Nano-15 downregulated the gene expression of inflammatory cytokines and pro-inflammatory M1 markers, while upregulating the gene expression of pro-healing M2 markers, autophagy markers, and growth factors of MΦs. A further investigation conducted using a specialized specimen-conditioned medium (SCM) from MΦs/ECs disclosed that the SCM derived from Nano-15 was able to manipulate a favorable microenvironment to facilitate MΦ-EC crosstalk via downregulation of inflammation-related gene expression and upregulation of function-related gene expression in ECs. Moreover, we further investigated the hemocompatibility of specimens in an ex vivo animal model. The results indicated that both pure Ti and Nano-15 possess satisfactory hemocompatibility, as manifested by the few thrombi that formed around the specimens. Additionally, in comparison with Nano-120, Nano-15 can significantly alleviate platelet activation and manipulate a loose structure of fibrin fibers in a dynamic situation. This study suggests that the application of Nano-15 as a surface coating for coronary stents may be a promising strategy for preventing ISR.