In vitro and in vivo evaluation of antibacterial activity of polyhexamethylene guanidine (PHMG)-loaded TiO2 nanotubes

Abstract

Artificial joint replacement is an effective surgical method for treating end-stage degenerative joint diseases, but peripheral bacterial infection of prosthesis can compromise the effect of the surgery. Herein, antibacterial effects of titanium dioxide nanotubes (TNTs) coated with polyhexamethylene guanidine (PHMG) were examined via in vitro and in vivo experiments. TNTs with a pore diameter 46.4 ± 5.9 nm and length of 300–500 nm for the slice and 650–800 nm for the rod were fabricated by anodization. Then, 3.46 ± 0.40 mg and 1.27 ± 0.28 mg of PHMG were coated onto the TNT slice and rod, respectively. In vitro studies of the release of PHMG showed that the antibacterial agent was released in two stages: initial burst release and relatively slow release. In vitro and in vivo antibacterial studies showed that the PHMG-loaded TNTs (PHMG-TNTs) had excellent antibacterial abilities to prevent bacterial infections. Clinical pathological analysis of rabbit femurs indicated that the implanted PHMG-TNTs had no apparent pathological changes. Real-time quantitative reverse transcription polymerase chain reaction analysis of the femur tissues around the implants showed that the expression of osteogenic-related genes, including runt-related transcription factor 2, osteocalcin, alkaline phosphatase, bone sialoprotein, bone morphogenetic protein 2 and vascular endothelial growth factor A, was significantly upregulated in the PHMG-TNT implanted group as compared to the other groups. Overall, these findings provide a promising approach for the fabrication of antibacterial and bone biocompatible titanium-based implants in orthopedics.