Immunomodulation effect of a hierarchical macropore/nanosurface on osteogenesis and angiogenesis

Immune systems play pivotal roles in determining the in vivo osseointegration of bone implants. While much evidence has shown that hierarchical implant surfaces can exhibit excellent osteogenic ability, their immune response has not been well elucidated, which will preclude accurate knowledge of their osseointegration performance. In this study, the immunomodulatory properties of a hierarchical macropore/nanosurface as well as the detailed mechanism was investigated. Macrophages were found to switch to M2 phenotype on the hierarchical surface, and decreased levels of inflammatory gene expression as well as increased expression of anti-inflammatory genes were endowed, which were probably regulated by the decisive role of cytoskeleton tension induced by specific cell shape. In addition, enhanced osteogenic differentiation of bone marrow mesenchymal stem cells and angiogenesis of human umbilical vein endothelial cells could be observed when stimulated by a RAW cells/hierarchical surface conditioned medium, which were probably due to increased expression of BMP-2 and VEGF of RAW cells, respectively. These findings give comprehensive knowledge into detailed mechanism of the immunomodulatory behavior of the hierarchical surface, which will also provide insight into the surface design of advanced bone biomaterials with satisfactory immunomodulation properties.