Micro-patterned titanium coatings with a grid-like structure doped with vancomycin against bacteria and affecting osteogenic differentiation

Abstract

Titanium and its alloy are widely used in orthopedic surgery. However, Ti implant-associated infections continue to be the primary cause of titanium implant failure. The present study aimed to investigate the effects of micro-patterned titanium coatings doped with vancomycin on antibacterial activity and osteogenic differentiation and to improve the bioactivity of the inert titanium. A micro-pattern was fabricated on titanium, then calcium phosphate bone cement and vancomycin were doped on the micro-patterned titanium with a grid-like structure on the surface for anti-bacterial activity. Staphylococcus aureus and methicillin-resistant S. aureus were applied to investigate the bacterial adhesion and biofilm formation at 6 h, 24 h, 3 d and 7 d using the spread plate method, confocal laser scanning microscopy and scanning electron microscopy. Human bone marrow mesenchymal stem cells were used for investigating the cell biocompatibility and osteogenic differentiation of the titanium substrate. The result showed that vancomycin could release on the micro-patterned titanium within 6 d and the burst release was reduced. The calcium phosphate bone cement-vancomycin doped micro-patterned titanium with a grid-like structure could resist bacterial infection for 7 d. The osteogenic differentiation of human bone marrow mesenchymal stem cells with the titanium substrate was analysed by the alkaline phosphatase activity and alizarin red staining semi-quantitative analysis of the micro-patterned Ti (Tp) and the CPC-VCM doped micro-pattern Ti (TV), and was demonstrated to be higher than that of the Ti without patterning (T0) at 7 d and 14 d, respectively. The real-time PCR also indicated that the Tp and TV upregulated human alkaline phosphatase, type I collagen at 7 d and osteopontin were also upregulated after incubation for 14 d. The in vitro study indicated that calcium phosphate bone cement-vancomycin doped on the micro-patterned titanium with a grid-like structure surface is a promising approach to fabricate multi-biofunctional titanium against bacteria and promoting osteogenic differentiation.