title: Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis.
abstract: Infection is one of the most important causes of titanium implant failure in vivo A developing prophylactic method involves the immobilization of antibiotics, especially vancomycin, onto the surface of the titanium implant. However, these methods have a limited effect in curbing multiple bacterial infections due to antibiotic specificity. In the current study, enoxacin was covalently bound to an amine-functionalized Ti surface by use of a polyethylene glycol (PEG) spacer, and the bactericidal effectiveness was investigated in vitro and in vivo The titanium surface was amine functionalized with 3-aminopropyltriethoxysilane (APTES), through which PEG spacer molecules were covalently immobilized onto the titanium, and then the enoxacin was covalently bound to the PEG, which was confirmed by X-ray photoelectron spectrometry (XPS). A spread plate assay, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to characterize the antimicrobial activity. For the in vivo study, Ti implants were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and implanted into the femoral medullary cavity of rats. The degree of infection was assessed by radiography, micro-computed tomography, and determination of the counts of adherent bacteria 3 weeks after surgery. Our data demonstrate that the enoxacin-modified PEGylated Ti surface effectively prevented bacterial colonization without compromising cell viability, adhesion, or proliferation in vitro Furthermore, it prevented MRSA infection of the Ti implants in vivo Taken together, our results demonstrate that the use of enoxacin-modified Ti is a potential approach to the alleviation of infections of Ti implants by multiple bacterial species.
authors: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Bin'en
authors: B
authors: Nie
authors: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Teng
authors: T
authors: Long
authors: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Haiyong
authors: H
authors: Ao
authors: Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
authors: Jianliang
authors: J
authors: Zhou
authors: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Tingting
authors: T
authors: Tang
authors: Shanghai Key Laboratory of Orthopedic Implants, Department of Orthopedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China advbmp2@163.com.|Department of Joint Surgery and Sports Medicine, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors: Bing
authors: B
authors: Yue
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000069343:Bone-Implant Interface; D015365:Enoxacin / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005269:Femur / Q000187:drug effects / Q000382:microbiology / Q000601:surgery; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D011092:Polyethylene Glycols / Q000737:chemistry*; D011437:Propylamines / Q000737:chemistry; D019736:Prostheses and Implants / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012821:Silanes / Q000737:chemistry; D013203:Staphylococcal Infections / Q000382:microbiology / Q000517:prevention & control*; D013499:Surface Properties; D014025:Titanium / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D011437:Propylamines; D012821:Silanes; D015365:Enoxacin; D011092:Polyethylene Glycols; D014025:Titanium; C477625:amino-propyl-triethoxysilane
keywords: enoxacin; immobilization; methicillin-resistant Staphylococcus aureus; polyethylene glycol; prosthesis-related infection; titanium