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

Yang, Ying; Ao, Haiyong; Yang, Shengbing; Wang, Yugang; Lin, Wentao; Yu, Zhifeng; Tang, Tingting

doi:10.2147/ijn.s102752

Cited by 29 publications

(43 citation statements)

References 44 publications

(49 reference statements)

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“… 46 , 47 Our previous work also found that the nanotube arrays generated on the implants exhibited alleviated bone infection in vivo , which was similar to the antimicrobial performance of the NT-C in this study. 14 Therefore, it was necessary to use the HACC-loaded nanotube structure to prevent the development of bone infection in vivo. Although the hydrophilic interfaces of the biomaterials played positive roles in the bacterial adherence and biofilm formation inhibition in this study, the in vivo anti-infection potential of the implants depends on the antibacterial agents loaded in the nanotubes.…”

Section: Discussionmentioning

confidence: 99%

“…Forty-five specified pathogen-free grade 8-week-old male Sprague-Dawley rats (weighing 399.07±20.73 g) were randomly assigned to three independent groups ( n =15 for each group). According to the previously reported surgical procedures, 14 , 28 , 29 the left knee was exposed through a middle parapatellar incision after general anesthesia with an intraperitoneal injection of 1% pentobarbital sodium (100 mg·kg −1 body weight). The femoral medullary cavity was widened gradually with Kirschner rods to a diameter of 2.0 mm after the dislocation of the patellar.…”

Section: Methodsmentioning

confidence: 99%

“…Body weight and temperature were selected as the observational indices and were obtained from all 15 animals in each group. 14 , 23 Weight was measured on a precision scale (TCS, Shanghai, China), and body temperature was determined by a veterinary digital infrared thermometer (HRQ-S60, Zhengzhou, China). Knee joint swelling, skin exudation, and other inflammatory signs were regarded as the main local signs of infection.…”

Section: Methodsmentioning

confidence: 99%

“…The rods were placed in 5 mL PBS and then sonicated in an ultrasonic bath at 150 W (B3500S-MT, Shanghai, China) at a frequency of 50 Hz for 5 min, followed by rapid vortex mixing (Vortex Genie 2, Scientific Industries, New York, NY) at maximum power for 1 min to thoroughly dislodge the adhered bacteria. 14 , 29 The adhered bacteria in the collected solutions after ultrasonication were measured by the spread plate method as previously reported. 13 Then, the femurs after explantation were quickly frozen in liquid nitrogen and ground to a powder under sterile conditions.…”

Section: Methodsmentioning

confidence: 99%

“… 12 Our previous in vitro and in vivo studies revealed that gentamicin-loaded nanotubes on titanium substrates exhibited evident antibacterial activity for the two bacterial strains mentioned above. 13 , 14 However, the resistance to β-lactamase, aminoglycoside, lincosamide, trimethoprim, macrolide, tetracycline, and sulfonamide antibiotics in S. aureus and S. epidermidis is widespread in current orthopedics surgery. 15 , 16 Therefore, implants with good antibacterial capability, especially under methicillin-resistant stapthylococci infection, is critical to the successful fixation and healing of bone fractures in current orthopedic surgery.…”

Section: Introductionmentioning

confidence: 99%

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Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes

Yang

Wang

et al. 2016

Bone Res

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Infection is one of the major causes of failure of orthopedic implants. Our previous study demonstrated that nanotube modification of the implant surface, together with nanotubes loaded with quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC), could effectively inhibit bacterial adherence and biofilm formation in vitro. Therefore, the aim of this study was to further investigate the in vitro cytocompatibility with osteogenic cells and the in vivo anti-infection activity of titanium implants with HACC-loaded nanotubes (NT-H). The titanium implant (Ti), nanotubes without polymer loading (NT), and nanotubes loaded with chitosan (NT-C) were fabricated and served as controls. Firstly, we evaluated the cytocompatibility of these specimens with human bone marrow-derived mesenchymal stem cells in vitro. The observation of cell attachment, proliferation, spreading, and viability in vitro showed that NT-H has improved osteogenic activity compared with Ti and NT-C. A prophylaxis rat model with implantation in the femoral medullary cavity and inoculation with methicillin-resistant Staphylococcus aureus was established and evaluated by radiographical, microbiological, and histopathological assessments. Our in vivo study demonstrated that NT-H coatings exhibited significant anti-infection capability compared with the Ti and NT-C groups. In conclusion, HACC-loaded nanotubes fabricated on a titanium substrate show good compatibility with osteogenic cells and enhanced anti-infection ability in vivo, providing a good foundation for clinical application to combat orthopedic implant-associated infections.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes

Yang

Wang

et al. 2016

Bone Res

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Approaches based on passive and active antibacterial coating on titanium to achieve antibacterial activity

Qin

Nie

et al. 2018

J Biomedical Materials Res

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Titanium (Ti) and its alloys are widely applied as orthopedic implants for hip and knee prosthesis, fixation, and dental implants. However, Ti and its alloys are bioinert and susceptible to bacteria and biofilm formation. Strategies for improving the antibacterial properties of Ti can be divided into two approaches, namely, passive coating and active coating on the Ti surface. Passive coating on Ti mainly kills the bacteria in contact but does not kill plankton or bacteria dwell in the bone tissue around the Ti implant. Active coating mainly involves the release of antibacterial agents to kill the bacteria, but this may result in the development of bacterial resistance. Both strategies include advantages and disadvantages. This article reviews the current and potential future approaches for improving antibacterial activity on Ti. We mainly focus on current approaches for fabricating antibacterial Ti and its limitations and countermeasures, and provide direction for further studies of biofunctionalization of Ti with antibacterial properties. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2531-2539, 2018.

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Staphylococcus aureus Prosthetic Joint Infection Is Prevented by a Fluorine‐ and Phosphorus‐Doped Nanostructured Ti–6Al–4V Alloy Loaded With Gentamicin and Vancomycin

Auñón

Esteban

Doadrio

et al. 2019

Journal Orthopaedic Research

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Prosthetic joint infection (PJI) is one of the most devastating complications in orthopedic surgery. One approach used to prevent PJI is local antibiotic therapy. This study evaluates the antibiotic release, in vitro cytocompatibility and in vivo effectiveness in preventing PJI caused by Staphylococcus aureus (S. aureus) of the fluorine‐ and phosphorus‐doped, bottle‐shaped, nanostructured (bNT) Ti–6Al–4V alloy loaded with a mixture of gentamicin and vancomycin (GV). We evaluated bNT Ti–6Al–4V loading with a mixture of GV, measuring the release of these antibiotics using high‐performance liquid chromatography. Further, we describe bNT Ti–6Al–4V GV cytocompatibility and its efficacy against S. aureus using an in vivo rabbit model. GV was released from bNT Ti–6Al–4V following a Boltzmann non‐linear model and maximum release values were obtained at 240 min for both antibiotics. The cell proliferation of MCT3T3‐E1 osteoblastic cells significantly increased at 48 (28%) and 168 h (68%), as did the matrix mineralization (52%) of these cells and the gene expression of three of the most important markers related to bone differentiation (more than threefold for VEGF and BGLAP, and 65% for RunX) on bNT Ti–6Al–4V GV compared with control. In vivo study results show that bNT Ti–6Al–4V GV can prevent S. aureus PJI according to histopathological and microbiological results. According to our results, bNT Ti–6Al–4V loaded with a mixture of GV using the soaking method is a promising biomaterial with favorable cytocompatibility and osteointegration, demonstrating local bactericidal properties against S. aureus. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:588–597, 2020

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

Cited by 29 publications

References 44 publications

Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes

Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes

Approaches based on passive and active antibacterial coating on titanium to achieve antibacterial activity

Staphylococcus aureus Prosthetic Joint Infection Is Prevented by a Fluorine‐ and Phosphorus‐Doped Nanostructured Ti–6Al–4V Alloy Loaded With Gentamicin and Vancomycin

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