Hydrophilic titanium surface-induced macrophage modulation promotes pro-osteogenic signalling

Abstract

Objectives: As biomaterial-induced modulation of mediators of the immune response may be a potential therapeutic approach to enhance wound healing events, the aim of this study was to delineate the effects of titanium surface modification on macrophage phenotype and function. Material and methods: Rodent bone marrow-derived macrophages were polarized into M1 and M2 phenotypes and cultured on micro-rough (SLA) and hydrophilic modified SLA (modSLA) titanium discs. Macrophage phenotype and cytokine secretion were subsequently assessed by immunostaining and ELISA, respectively. Osteoblast gene expression in response to culture in the M1 and M2 macrophage conditioned media was also evaluated over 7 days by RT-PCR. Results: M1 macrophage culture on the modSLA surface promoted an M2-like phenotype as demonstrated by marked CD163 protein expression, Arg1 gene expression and the secretion of cytokines that significantly upregulated in osteoblasts the expression of genes associated with the TGF-ß/BMP signalling pathway and osteogenesis. In comparison, M2 macrophage culture on SLA surface promoted an inflammatory phenotype and cytokine profile that was not conducive for osteogenic gene expression. Conclusions: Macrophages are able to alter or switch their phenotype according to the signals received from the biomaterial surface. A hydrophilic micro-rough titanium surface topography elicits a macrophage phenotype associated with reduced inflammation and enhanced pro-osteogenic signalling.