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 aminefunctionalized 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.

<p>Nanosilver/poly (DL-lactic-co-glycolic acid) on titanium implant surfaces for the enhancement of antibacterial properties and osteoinductivity</p>

“…Although current antibiotics have been coated on orthopedic material surface to prevent infection, binding specificity of a designated bacteria to a specific conventional antimicrobial limits the clinical utility of local antibiotics. [18][19][20][21] Because a wide variety of bacterial species are responsible for implantassociated infections: Gram-positive Staphylococcus bacteria species (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus haemolyticus) and Gram-negative Pseudomonas aeruginosa and Escherichia coli, among which, S. aureus and P. aeruginosa are the two most common pathogens for implant infection. [22][23][24] Narrow-spectrum antibiotic therapies may fail to prevent all implant-associated infecting bacteria, while broad-spectrum antibiotic therapies may induce antibiotic resistance.…”

An antibiofilm coating of 5‐aryl‐2‐aminoimidazole covalently attached to a titanium surface

“…This imposes a significant economic burden on the health sector . Therefore, over the years numerous antibacterial coating strategies have been developed, such as silver‐coated implants, implants coated with chlorhexidine and iodine and antibiotic‐coated implants . However, due to increasing resistance development against the previously mentioned strategies, new antibiofilm coatings are needed .…”

A comparative analysis of antibacterial properties and inflammatory responses for the KR-12 peptide on titanium and PEGylated titanium surfaces

“…17 Polyethylene glycol (PEG) is a long chain polymer that is widely used in tissue engineering, medicine, food, owing to its high degree of hydrophilicity, water solubility, good biocompatibility and lack of toxicity. [23][24][25][26][27] The synthetic hydrophilic polymer PEG and its derivatives are the most widely used antifouling and anti-bacterial materials. AMPs can be covalently immobilised using PEG that bears functional groups suitable for covalent peptide immobilisation.…”