Dual-Purpose Magnesium-Incorporated Titanium Nanotubes for Combating Bacterial Infection and Ameliorating Osteolysis to Realize Better Osseointegration

ACS Biomater Sci Eng. 2019 Oct 14;5(10):5368-5383. doi: 10.1021/acsbiomaterials.9b00938. Epub 2019 Oct 2.

Abstract

Currently, implant-related bone infection characterized by aggravated bone resorption and osteolysis, remains a severe challenge in plastic and orthopedic surgery. Therefore, surface modification of implants endowed with both antibacterial potential and suppression of osteoclastogenesis offers new insight into relevant therapeutic strategies. In this study, we designed magnesium (Mg)-incorporated nanotube-modified titanium implants (NT-Mg) that combine dual-functional Mg with antimicrobial properties of titania nanotubes with specific diameter. The surface characterization, in vitro degradation, antibacterial properties, cytocompatibility, and inhibitory effects on osteoclastogenesis together with the in vivo anti-infection potential and osseointegration of the implants were systematically investigated. Our results demonstrated that NT-Mg implants maintained continuous and reliable release of Mg ion from the titania nanotubes (TNTs), producing long lasting antimicrobial activity. The nanotubular structure and alkaline microenvironment during degradation were the two main reasons responsible for the antimicrobial properties of NT-Mg. In addition, NT-Mg exhibited favored osteoprogenitor cell adhesion and proliferation without obvious cytotoxicity. Moreover, Mg2+ released in the degraded liquid suppressed osteoclastogenesis via down-regulation of NF-κB/NFATc1 signaling. Finally, we established an implant-related bone infection model to assess the in vivo anti-infection potential and osseointegration of the NT-Mg implant. As expected, NT-Mg implants significantly prevented bone infection and osteolysis, leading to improved osseointegration. Based on these promising findings, the dual-functional magnesium-incorporated titania nanotubes represent an efficient alternative to realize better osseointegration in severe implant-related bacterial infections.

Keywords: dual-functional; implant-related infection; magnesium; osseointegration; titania nanotubes.