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Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_15 | Pages 252 - 252
1 Mar 2013
Marouf M Saebnoori E Rahimi MK Shahrabi T Sanjabi S
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INTRODUCTION

Nickel-Titanium (NiTi) with a molar composition of 50:50 or nitinol alloy exhibit special mechanical properties. These properties can be put to excellent use in various biomedical applications including: intravascular stent, orthodontic wires, prosthetic heart valves, angioplastic guides, orthopaedic implants, bone substitution materials, endoscopic instruments, implant stents and filters. Microorganism adhesion properties of nitinol may be decreased by oxidizing agents and surface heat treatment. In the present study, we investigated the microorganism adhesion and cytotoxicity of the thin film of nitinol and compared these properties with that of bulk form.

METHODS

In this analytical comparative study, small parts of thin film and bulk form of nitinol (15 mm×15 mm) were selected and sterilized in autoclave (15 lb for 20 min). Five microorganism, four bacteria (Ecoli, staphylococcus aureus, pseudomonase aerugenosa, bacillus cereus) and one mold form of fungi (candida albicans) were selected. The sample materials (thin film and bulk forms of nitinol) were treated by microorganism suspensions in 37°C for 24h in different culture flasks. Every suspension of five microorganisms was counted before and after examination. Adherence activity of these forms of nitinol was studied by optical and electron microscopy. The interaction between the microorganisms and the two forms of nitinol alloy were studied by variation in number of microorganisms counted after introduction of these living organisms to the surface of the alloy.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 28 - 28
22 Nov 2024
Boyce S Nichol T Smith T Le Maitre C
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Aim. Periprosthetic joint infections follow 1-3% of arthroplasty surgeries, with the biofilm nature of these infections presenting a significant treatment challenge. 1. Prevention strategies include antibiotic-loaded bone cement; however, increases in cementless procedures means there is an urgent need for alternative local antimicrobial delivery methods. 2. A novel, ultrathin, silica-based sol-gel technology is evaluated in this research as an anti-infective coating for orthopaedic prosthetic devices, providing local antibiotic release following surgery. Method. Reduction in clinically relevant microbial activity and biofilm reduction by antimicrobial sol-gel coatings, containing a selection of antibiotics, were assessed via disc diffusion and microdilution culture assays using the Calgary biofilm device. 3. Proliferation, morphology, collagen, and calcium production by primary bovine osteoblasts cultured upon antibiotic sol-gel surfaces were examined, and cytotoxicity evaluated using Alamar blue staining and lactate dehydrogenase assays. Concentrations of silica, calcium and phosphorus compounds within the cell layer cultured on sol-gel coatings and concentrations eluted into media, were quantified using ICP-OES. Furthermore, cellular phenotype was assessed using alkaline phosphatase activity with time in culture. Results. Low antibiotic concentrations within sol-gel had an inhibitory effect on clinically relevant biofilm growth, for example 0.8 mg ml. -1. tobramycin inhibited clinically isolated S. aureus (MRSA) growth with an 8-log reduction in viable colony forming units. There was no significant difference in metabolic activity between untreated and sol-gel exposed primary bovine osteoblasts in elution-based assays. Reduction (2-fold) in metabolic activity in direct contact assays after 48 hours exposure was likely to be due to increased osteoinduction, whereas no impact upon cell proliferation were observed (p=0.92 at 14 days culture). The morphology of primary osteoblasts was unaffected by culture on sol-gel coatings and collagen production was maintained. Calcium containing nodule production within bovine osteoblastic cells was increased 16-fold after 14 days culture upon sol-gel. Conclusions. The ultrathin sol-gel coating showed low cytotoxicity, strong biofilm reducing activity and antimicrobial activity, which was comparable to antibiotics alone, demonstrating that sol-gel delivery of antibiotics could provide local antimicrobial effects to inhibit PJI growth without the need for bone cement. Future work will develop and evaluate sol-gel performance in an ex vivo explant bone infection model which will reduce the need for animal experimentation


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_19 | Pages 66 - 66
22 Nov 2024
Ye Z van der Wildt B Vogely C Weinans H Poot A van der Wal B
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Aim. Prosthetic joint infections (PJI) remain a great challenge in orthopedic surgery with a high mortality rate. It is particularly complicated by biofilms and infections caused by Methicillin-resistant Staphylococcus aureus (MRSA). It concurrently shields bacteria from host immune responses and confers resistance to antibiotics. This study aims to investigate the efficacy of radioimmunotherapy as an innovative therapeutic modality to address the challenges posed by MRSA and its biofilm. Method. We induced specific monoclonal antibodies 4497-IgG1 as carriers, which target wall teichoic acids (WTA) existing on MRSA and its biofilm. Radionuclides actiniumr-225 (. 225. Ac, α-emitter) and lutetium-177 (. 177. Lu, β-emitter) were conjugated with mAbs using DOTA as chelator. Quality control was assessed using thin layer chromatography and immunoreactivity assays. . 225. Ac- and . 177. Lu-labelled 4497-IgG1 were employed to evaluate the susceptibility of MRSA and its biofilm to the radioimmunotherapy in vitro. Planktonic MRSA and biofilms, at concentrations of 10. 8. and 10. 7. CFU/mL, were incubated at 37°C for 60 minutes in PBS containing either . 225. Ac-mAb (0 - 14.8 kBq) or . 177. Lu-mAb (0 - 14.8 MBq). Radiolabelled dunituximab and free radionuclides serve as isotype-matched negative control. The bacterial viability and metabolic activity were subsequently quantified using CFU and XTT assays. Results. The radiochemical purity of the . 225. Ac-mAbs and . 177. Lu-mAbs complex were determined to be 95.4% and 96.16%. Immunoreactivity fractions of them were measured at 81.8% and 80.8%. . 225. Ac-mAbs and . 177. Lu-mAbs exhibited significant and dose-dependent antimicrobial effects on both planktonic MRSA and biofilm. . 225. Ac- and . 177. Lu-4497IgG1 at doses of 7.4 kBq and 7.4 MBq resulted in more than 4-log reduction in bacterial counts. In biofilms, 2-log reduction at the highest . 225. Ac radioactivity of 14,8kBq. The . 177. Lu complex showed a strong dose-dependent effect, with a reduction of up to 4-log. The XTT assay confirmed these findings, showing a decrease in metabolic activity corresponding to a decrease in bacterial counts, and a slight increase in metabolic activity at the lower dose. Conclusions. Our study demonstrates the efficacy of . 225. Ac and . 177. Lu-labelled 4497-IgG1 antibodies in mediating dose-dependent bactericidal effects against planktonic MRSA and biofilms in vitro. This indicates that radioimmunotherapy could be a potential targeted therapeutic strategy against MRSA and its biofilm. Further research in preclinical and clinical settings is warranted to validate and refine these findings on biofilm-associated implant infections


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 93 - 93
1 Dec 2019
Jensen LK Henriksen NL Blirup SA Jensen HE
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Aim. To conduct a systematic review of non-rodent animal models (rabbit, pig, dog, goat and sheep) of bone infection. In the future, anti-infective technologies aiming to fight bone infections are depending on evaluation in reliable animal models. Therefore, it is highly relevant to evaluate the scientific quality of existing bone infection models. Method. PubMed and Web of Science were searched systematically. To be included in the systematic review, publications had to deal with bacterial inoculation of non-rodent animals in order to model bone infections in humans. Data was extracted on study design e.g. bacterial inoculation dose and infection time, methodological quality and post-mortem evaluation with respect to registration and quantification of pathology and microbiology. Results. In total, 316 publications were included in the systematic review. A substantial lack of study design information (e.g. bacterial identity and infection time) was demonstrated in many of the papers, which hampers reproducibility and continuation of the established work. Furthermore, the methodological study quality was found to be low as definition of infection, randomization, power analysis and blinding were only seldom reported. The use of histology has increased in recent years, but a semi-quantitative scoring of the lesions was often missing, i.e. no objective quantification of outcome. Most of the studies focused on whether the inoculated bacteria were present within the bone tissue post mortem or not. However, very often the bacterial burden was not quantified. In many of the models, different antimicrobial interventions were examined, and the lack of quantitative microbiology makes it difficult to estimate and reproduce the effects objectively. Although, antimicrobial effects were described for most interventions, a lack of sterile outcome was observed in many models. Failure to report a sterile outcome reduces the possibility for obtaining valuable knowledge regarding effective antibiotic doses in-vivo. Based on the present review a standard study template guideline for animal models of bone infections was established. The guideline describes details related to the animal, pathogen, animal + pathogen (infected animal) and post mortem analysis that are of crucial importance for validation of results and reproducibility. Conclusions. Due to a substantial lack of uniformity we miss the opportunity to get maximal knowledge from the preclinical literature. The new guideline will improve reproducibility of future models and translation of findings to the clinical setting. Bone infection organisations/societies and journal editors should encourage compliance with the new guideline. Reference: JBJS, 2019, In press


The Bone & Joint Journal
Vol. 97-B, Issue 5 | Pages 582 - 589
1 May 2015
Brennan SA Ní Fhoghlú C Devitt BM O’Mahony FJ Brabazon D Walsh A

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications. Cite this article: Bone Joint J 2015; 97-B:582–9