Rapid inactivation of multidrug-resistant bacteria and enhancement of osteoinduction via titania nanotubes grafted with polyguanidines

The rapid in situ inhibition of bacterial contamination and subsequent infection without inducing drug resistance is highly vital for the successful implantation and long-term service of titanium (Ti)-based orthopedic implants. However, the instability and potential cytotoxicity of current coatings have deterred their clinical practice. In this study, anodic oxidized titania nanotubes (TNT) were modified with antibacterial polyhexamethylene guanidine (PG) with the assistance of 3,4-dihydroxyphenylacetic acid. Interestingly, the prepared TNT-PG coating exhibited superior in vitro antibacterial activity than flat Ti-PG coating and effectively killed typical pathogens such as Escherichia coli and superbug methicillin-resistant Staphylococcus aureus with above 4-log reduction (> 99.99 % killed) in only 5 min. TNT-PG coating also exerted excellent hemocompatibility with red blood cells and nontoxicity toward mouse pre-osteoblasts (MC3T3-E1) in 1 week of coculture. In addition, the efficient in vivo anti-infective property of this coating was observed in a rat subcutaneous infection model. More importantly, TNT-PG coating improved the expression of alkaline phosphatase and enhanced the extracellular matrix mineralization of pre-osteoblasts, denoting its osteoinductive capacity. This versatile TNT-PG coating with excellent antibacterial activity and biocompatibility could be a promising candidate for advanced orthopedic implant applications.