Effects of titanium surface roughness on the mediation of osteogenesis via modulating the immune response of macrophages

Osteoblastic lineage cells are commonly used to evaluate the in vitro osteogenic ability of bone biomaterials. However, contradictory results obtained from in vivo and in vitro studies are not uncommon. With the increasing understanding of osteoimmunology, the immune response has been recognized as playing an important role in bone regeneration. In this study, we examined the effect of submicron-scaled titanium surface roughness (ranging from approximately 100 to 400 nm) on the response of osteoblasts and macrophages. The results showed that osteoblast differentiation enhanced with increased surface roughness of titanium substrates. The cytoskeleton of macrophages altered with the variation in titanium surface roughness. The production of cytokines (TNF-alpha, IL-6, IL-4 and IL-10) could be regulated by titanium surface roughness. Moreover, macrophages cultured on titanium surfaces exhibited a tendency to polarize to M1 phenotype with the increase of surface roughness. Material/macrophage conditioned medium tended to promote osteoblast differentiation with the increase of surface roughness. The results indicate that increasing surface roughness in the submicron range is beneficial for osteogenesis via modulating the immune response of macrophages. Modifying biomaterial surfaces based on their immunomodulatory effects is considered as a novel strategy for the improvement of their biological performance.