Self-assembled nanosheets on NiTi alloy facilitate endothelial cell function and manipulate macrophage immune response

Abstract

Stenting has been widely adopted for the treatment of cardiovascular diseases, but the complications such as in-stent restenosis and late stent thrombosis cannot be completely avoided, which are closely related to endothelial dysfunction and inflammatory response. In the present work, oxide nanosheets were grown on the surface of nearly equiatomic NiTi alloy by alkaline corrosion (AC), aiming at yielding favorable endothelial functionality and immune microenvironment. The results show nanosheets mainly composed of TiO2, Ni(OH)2, and K2TiO3 can be grown on the alloy in KOH solution of 2.5–15 M at room temperature. The AC-treated samples significantly promote endothelial cell (EC) functionality such as proliferation, migration, NO production, VEGF secretion, and angiogenesis. In addition, the sample grown in KOH of 15 M can switch macrophages to an anti-inflammatory M2 phenotype and up-regulate the gene expression of VEGF to facilitate EC functionality. These results demonstrate that the nanosheets can directly and indirectly up-regulate EC functionality, possibly leading to rapid re-endothelialization of the stents thus addressing the stent-related complications.