Regulation of macrophage polarization and functional status by modulating hydroxyapatite ceramic micro/nano-topography

Recent studies on osteoimmunology have revealed the indispensable role of immune cells in osteogenesis. The surface topography of biomaterials plays a critical role in regulating cellular behaviors; however, little attention is paid to its effects on the immune response. Three dense hydroxyapatite (HA) disks with grain size in nano-scale (∼100 nm) to submicron (∼500 nm) range were prepared to investigate their role in macrophage polarization and functional status. It was found that HA ceramics with nano-topography promoted macrophage phenotypic switching from the pro-inflammatory M1 type to the pro-healing M2 type. A reduction in grain size could significantly inhibit the secretion of pro-inflammatory cytokine and increase the proportion of CD206+ M2 population in vitro. Meanwhile, nano-topography could reduce tissue inflammation, up-regulate gene expression of M2 phenotypic marker, and raise the fraction of ARG+ M2 macrophages in vivo. This might be attributed to the differential integrin expression to regulate the activation of intracellular signaling cascades. These findings indicate that the surface topography of HA ceramics regulates macrophage responses, thereby adjusting inflammation and subsequent tissue regeneration. An improved understanding of the relationship between material features and its immunomodulatory potential may help to design bone substitute materials with good biological performance.