“Cortex-Like” Topography Of Implants Improved Osseointegration Via Macrophages Polarization

The purpose of this study is to investigate the effect of “cortex-like” micro/nano topography of titanium implants on the behaviours of macrophge which can regulate inflammatory response and influence osseointegration. The TiO2 “cortex-like” coating was fabricated using sodium tetraborate electrolytes through micro-arc oxidation. RAW264.7 cells were respectively cultured on the polished titanium (Ti-P), the “volcano-like” titanium (Ti-V), the “cortex-like” titanium (Ti-C) to observe the macrophage polarization by FE-SEM, immunofluorescence, RT-qPCR and detect cytokine secretion by RT-qPCR. We used alkaline phosphatase stain, alizarin red stain and RT-qPCR analysis to evaluate osteoblast differentiation in condition medium. The impacts of the “cortex-like” coating on the immune environment, angiogenesis, and osteogenesis were evaluated in an animal study by H&E, masson, immunohistochemistry and immunofluorescence staining. Ti-C groups exhibited significant boost in mocrophage proliferation. Higher expression of CD206 and lower of CD86 were observed in Ti-C groups. Ti-C groups mainly actived the alternatively actived pathway to generate M2 phenotypes, which was characterized by ascending the level of IL-10, and decreasing of TNF-α. Osteoblast related-protein COL1,OCN,RUNX2,BMP2,ALP expression, ALP activity, mineralization formation in vitro and bone formation in vivo manifested TI-C> Ti-V> TI-P. “Cortex-like” coating on titanium implants participate in osseointegration through inducing the discrepency of macrophage polarization in the immune microenviroment. “Cortex-like” coating enhence osseointegration and mediate anti-inflammatory regulation providing a new idea to optimize implants.