Evaluating the osteoimmunomodulatory properties of micro-arc oxidized titanium surface at two different biological stages using an optimized in vitro cell culture strategy.

It is known that introducing a porous ceramic coating on titanium (Ti) implant surface fabricated by micro-arc oxidation (MAO) could enhance the differentiation of osteoblasts. However, the osteogenic capacity of MAO-fabricated coating still remains unknown when immune cells especially macrophages are involved. The influence of the inflammatory microenvironment and the co-influence of the inflammatory microenvironment and surface characteristics of MAO-fabricated coating on osteoblast response need to be explored. In this study, a new in vitro cell culture strategy is proposed by mimicking the biological events happened after implantation based on the recruitment of osteoblasts to biomaterial surfaces to investigate biological performances of MAO-modified Ti surface. It is found that macrophages grown on MAO-modified Ti surface were switched to M1-like phenotype, evidenced by the promoted expressions of inflammatory genes (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β) and production of pro-inflammatory cytokine TNF-α. Moreover, the inflammatory microenvironment created by macrophage/MAO-modified Ti surface interactions could promote the collagen syntheses and matrix mineralization of osteoblast-like cells grown tissue culture plate. When osteoblasts were cultured on MAO-modified Ti surface and cultured by macrophage/MAO-modified Ti surface conditioned medium (CM), the alkaline phosphatase (ALP) activity and collagen synthesis of osteoblast-like cells were promoted. This study suggests that MAO-modified Ti surface is beneficial for osteogenesis at both stages after implantation (before and after osteoblast recruitment to biomaterial surfaces).