Icariin/Aspirin Composite Coating on TiO2 Nanotubes Surface Induce Immunomodulatory Effect of Macrophage and Improve Osteoblast Activity

Surface coating modification of titanium-based alloys is an efficient way to accelerate early osseointegration in dental implant fields. Icariin (ICA) is a traditional Chinese medicine that has bone activating functions, while aspirin (ASP) is a classical non-steroidal anti-inflammatory drug with good antipyretic and analgesic capabilities. Moreover, poly(lactic-co-glycolic acid) (PLGA) has attracted great attention due to its excellent biocompatibility and biodegradability. We superimposed an ASP/PLGA coating onto ICA loaded TiO2 nanotubes structure so as to establish an icariin/aspirin composite coating on TiO2 nanotubes surface. Scanning electron microscopy, X-ray photoelectron spectroscopy, a contact angle test and a drug release test confirmed the successful preparation of the NT-ICA-ASP/PLGA substrate, with a sustained release pattern of both ICA and ASP. Compared to those cultured on the Ti surface, macrophage cells on the NT-ICA-ASP/PLGA substrate displayed decreased M1 proinflammatory and enhanced M2 proregenerative genes and proteins expression, which implied activated immunomodulatory effect. Moreover, when cultured with conditioned medium from macrophages, osteoblast cells on the NT-ICA-ASP/PLGA substrate revealed improved cell proliferation, adhesion and osteogenic genes and proteins expression, compared with those on the Ti surface. The abovementioned results suggest that the established NT-ICA-ASP/PLGA substrate is a promising candidate for functionalized coating material in Ti implant surface modification.