Engineering nano-structures with controllable dimensional features on micro-topographical titanium surfaces to modulate the activation degree of M1 macrophages and their osteogenic potential

Modulating the activation state and degree of macrophages still remains as a challenge for the topographical design of Ti-based implants. In this work, micro/nano-structured coatings were prepared on Ti substrates by micro-arc oxidation (MAO) and subsequent hydrothermal (HT) treatment. By varying the HT conditions, plate-like nano-structures with an average length of 80, 440 or 780 nm were obtained on MAO-prepared micro-topographical surfaces. Depending on the dimensional features of nano-plates, the specimens were noted as Micro, Micro/Nano-180, Micro/Nano-440 and Micro/Nano-780, respectively. The in vitro results showed that the activation state and degree of macrophages could be effectively modulated by the micro/nano-structured surfaces with various dimensional features. Compared to the Micro surface, the Micro/Nano-180 surface activated both M1 and M2 phenotype in macrophages, while the Micro/Nano-440 and Micro/Nano-780 surfaces polarized macrophages to their M1 phenotype. The activation degree of M1 macrophages followed the trend: Micro < Micro/Nano-180 < Micro/Nano-440 < Micro/Nano-780. However, the osteogenic potential of the activated macrophages in response to various surfaces were in the order: Micro ≈ Micro/Nano-780 < Micro/Nano-180 < Micro/Nano-440. Together, the findings presented in this work indicate that engineering nano-structures with controllable dimensional features is a promising strategy to modulate macrophage activation state and degree. In addition, it is essential to determine the appropriate activation degree of M1 macrophages for enhanced osteogenesis.