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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 6 - 6
2 Jan 2024
Orellana F Grassi A Wahl P Nuss K Neels A Zaffagnini S Parrilli A
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A comprehensive understanding of the self-repair abilities of menisci and their overall function in the knee joint requires three-dimensional information. However, previous investigations of the meniscal blood supply have been limited to two-dimensional imaging methods, which fail to accurately capture tissue complexity. In this study, micro-CT was used to analyse the 3D microvascular structure of the meniscus, providing a detailed visualization and precise quantification of the vascular network.

A contrast agent (μAngiofil®) was injected directly into the femoral artery of cadaver legs to provide the proper contrast enhancement. First, the entire knee joint was analysed with micro-CT, then to increase the applicable resolution the lateral and medial menisci were excised and investigated with a maximum resolution of up to 4 μm. The resulting micro-CT datasets were analysed both qualitatively and quantitatively. Key parameters of the vascular network, such as vascular volume fraction, vessel radius, vessel length density, and tortuosity, were separately determined for the lateral and medial meniscus, and their four circumferential zones defined by Cooper.

In accordance with previous literature, the quantitative micro-CT data confirm a decrease in vascular volume fraction along the meniscal zones. The highest concentration of blood vessels was measured in the meniscocapsular region 0, which is characterized by vascular segments with a significantly larger average radius. Furthermore, the highest vessel length density observed in zone 0 suggests a more rapid delivery of oxygen and nutrients compared to other regions. Vascular tortuosity was detected in all circumferential regions, indicating the occurrence of vascular remodelling in all tissue areas.

In conclusion, micro-CT is a non-invasive imaging technique that allows for the visualization of the internal structure of an object in three dimensions. These advanced 3D vascular analyses have the potential to establish new surgical approaches that rely on the healing potential of specific areas of the meniscus.

Acknowledgements: The authors acknowledge R. Hlushchuk, S. Halm, and O. Khoma from the University of Bern for their help with contrast agent perfusions.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims

There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO4) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO4 applied locally to treat ODAI.

Methods

A total of 30 operations with ceftriaxone-loaded CaSO4 had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS).


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 40 - 40
1 Dec 2021
Wiesli M Kaiser J Gautier E Wick P Maniura K Rottmar M Wahl P
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Aim

Implant-associated infection usually require prolonged treatment or even removal of the implant. Local application of antibiotics is used commonly in orthopaedic and trauma surgery, as it allows reaching higher concentration in the affected compartment, while at the same time reducing systematic side effects. Ceftriaxone release from calcium sulphate has a particularly interesting, near-constant release profile in vitro, making it an interesting drug for clinical application. Purpose of the present study was to investigate the potential cytotoxicity of different ceftriaxone concentrations and their influence on osteogenic differentiation of human pre-osteoblasts.

Method

Human pre-osteoblasts were cultured up to 28 days in different ceftriaxone concentrations, ranging between 0 mg/L and 50’000 mg/L. Cytotoxicity was determined quantitatively by measuring lactate dehydrogenase release, metabolic activity, and cell proliferation. Gene expression analysis of bone-specific markers as well as mineralization and protein expression of collagen-I (Col-I) were investigated to assess osteogenic differentiation.


Bone & Joint Research
Vol. 10, Issue 3 | Pages 218 - 225
1 Mar 2021
Wiesli MG Kaiser J Gautier E Wick P Maniura-Weber K Rottmar M Wahl P

Aims

In orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells.

Methods

Human preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied.


Bone & Joint Research
Vol. 10, Issue 2 | Pages 96 - 104
28 Jan 2021
Fang X Zhang L Cai Y Huang Z Li W Zhang C Yang B Lin J Wahl P Zhang W

Aims

Microbiological culture is a key element in the diagnosis of periprosthetic joint infection (PJI). However, cultures of periprosthetic tissue do not have optimal sensitivity. One of the main reasons for this is that microorganisms are not released from the tissues, either due to biofilm formation or intracellular persistence. This study aimed to optimize tissue pretreatment methods in order to improve detection of microorganisms.

Methods

From December 2017 to September 2019, patients undergoing revision arthroplasty in a single centre due to PJI and aseptic failure (AF) were included, with demographic data and laboratory test results recorded prospectively. Periprosthetic tissue samples were collected intraoperatively and assigned to tissue-mechanical homogenization (T-MH), tissue-manual milling (T-MM), tissue-dithiothreitol (T-DTT) treatment, tissue-sonication (T-S), and tissue-direct culture (T-D). The yield of the microbial cultures was then analyzed.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 296 - 306
1 May 2017
Samara E Moriarty TF Decosterd LA Richards RG Gautier E Wahl P

Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Methods

In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 66 - 66
1 Dec 2016
Samara E Moriarty F Decosterd LA Richards G Gautier E Wahl P
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Aim

Thermal stability is a key property determining the suitability of an antibiotic agent for local application. Long-term data describing thermal stability without interference from carrier materials are scarce.

Method

In this study, a total of 38 common antibiotic agents have been maintained at 37 °C in saline solution, and degradation and antibacterial activity assessed over 6 weeks. The impact of an initial supplementary heat exposure mimicking exothermically-curing bone cement has also been tested. Antibiotic degradation was assessed by chromatography coupled to mass spectrometry or immunoassays, as appropriate. Antibacterial activity was determined by Kirby-Bauer disk diffusion assay.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 84 - 84
1 Dec 2016
Wahl P Post V Richards G Moriarty F
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Aim

Determine the time concentration profile required to achieve vancomycin-mediated eradication of Staphylococcus aureus biofilm. This is critical for the identification of performance targets for local antibiotic delivery, yet has not been described.

Method

Mature S. aureus UAMS-1 biofilms were grown on titanium-aluminum-niobium discs in Mueller Hinton broth (MHB). After 7 days, the discs were incubated in MHB containing vancomycin at 100, 200, 500, 1′000 and 2′000 mg/L. Both static and shaking conditions were tested. Samples were retrieved at intervals for up to 28 days for quantification of residual biofilm by sonication and serial dilution plating. One additional disc was processed per time point for scanning electron microscopy.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 283 - 283
1 Jul 2014
Post V Wahl P Uckay I Zimmerli W Corvec S Loiez C Ochsner P Moriarty F
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Summary

Staphylococcus aureus isolates from Fracture fixation device related infections contained fewer isolates that form a strong biofilm in comparison with isolates from Prosthetic joint infections. Both orthopaedic implant related infection groups possessed fnbB and sdrE more frequently than the non-implant related infection groups.

Introduction

One of the most common pathogen causing musculoskeletal infections is Staphylococcus aureus. The aim was to characterise S. aureus isolated from these infections and to look for differences between the isolates from orthopaedic implant related infections (OIRI) and those in non-implant related infections (NIRI). The OIRI are further differentiated in those associated with fracture fixation (FFI) devices and those found in prosthetic joint infections (PJI).


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVII | Pages 79 - 79
1 Sep 2012
Wahl P Livio F Jacobi M Gautier E Buclin T
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Introduction

Calcium sulphate is a resorbable void filler that can be used for local antibiotic delivery.

Results from clinical studies on chronic osteomyelitis thus treated with local vancomycin have already been published. Despite significant exposure to this drug, there are no pharmacokinetic studies published so far. Based on observations in our patients, a model predicting vancomycin serum and wound fluid levels and toxicity potential is presented.

Methods

Following implantation of Osteoset® added with vancomycin, serum and wound fluid concentrations of this antibiotic have been monitored systematically. The pharmacokinetic analysis was performed using a non-linear mixed-effects model based on a one-compartment model with first-degree absorption.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 609 - 609
1 Oct 2010
Wahl P Gautier E Livio F
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Introduction: Purified plaster of Paris can be used as a resorbable carrier material for local antibiotic therapy. Clinical use already has been published with vancomycin and the aminoglycosides gentamycin and tobramycin. Calcium sulphate pellets with vancomycin can be manufactured during operation from Osteoset® and vancomycin powder, whereas calcium sulphate with tobramycin is available as ready-to-use pellets under the brand name Osteoset T®. Results are promising. However, no data on systemic serum levels in humans have been published so far, despite well known toxicity issues of these antibiotics in systemic therapy.

Methods: Following implantation of calcium sulphate with vancomycin or tobramycin, systemic serum levels of these antibiotics have been measured for up to 10 days, and prospectively gathered. Considering serum levels and renal function, pharmacokinetics have been estimated.

Results: Between August 2006 and February 2008, calcium sulphate with vancomycin has been implanted in 15 patients, and with tobramycin in 12 patients. Whereas vancomycin levels remained very low, tobramycin levels close to the usually accepted trough levels could be observed at 24h post-operation.

Conclusion: Vancomycin added to calcium sulphate has a safe systemic profile. On the contrary, significant serum levels of tobramycin can be measured more than 24h after implantation. Caution is mandatory when using this antibiotic, and explantation should be considered if levels too high are observed.