In vivo evaluation of the anti-infection potential of gentamicin-loaded nanotubes on titania implants

Ying Yang,1 Hai-yong Ao,1 Sheng-bing Yang,1 Yu-gang Wang,1 Wen-tao Lin,2 Zhi-feng Yu,1 Ting-ting Tang1 1Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 2Department of Orthopedics, Fuzhou Second Hospital, Affiliated Hospital of Xiamen University, Fuzhou, People’s Republic of China Abstract: Titanium-based implants have been widely used in orthopedic surgery; however, failures still occur. Our in vitro study has demonstrated that gentamicin-loaded, 80nm-diameter nanotubes possessed both antibacterial and osteogenic activities. Thus, the aim of this study was to further investigate the in vivo anti-infection effect of the titanium implants with gentamicin-loaded nanotubes. Thirty-six male Sprague Dawley rats were used to establish an implant-associated infection model. A volume of 50µL Staphylococcus aureus suspension (1×105CFU/mL) was injected into the medullary cavity of the left femur, and then the titanium rods without modification (Ti), titanium nanotubes without drug loading (NT), and gentamicin-loaded titanium nanotubes (NT-G) were inserted with phosphate-buffered saline-inoculated Ti rods as a blank control. X-ray images were obtained 1day, 21days, and 42days after surgery; micro-computed tomography, microbiological, and histopathological analyses were used to evaluate the infections at the time of sacrifice. Radiographic signs of bone infection, including osteolysis, periosteal reaction, osteosclerosis, and damaged articular surfaces, were demonstrated in the infected Ti group and were slightly alleviated in the NT group but not observed in the NT-G group. Meanwhile, the radiographic and gross bone pathological scores of the NT-G group were significantly lower than those of the infected Ti group (P