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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 108 - 108
14 Nov 2024
Marchiori G Zaffagnini S Cavazza L Fabbro GD Grassi A Lopomo NF Giavaresi G Maglio M
Full Access

Introduction. Histology is still considered the gold standard method for the evaluation of soft tissues in the musculoskeletal field, thanks to the possibility of studying structures using different staining and high magnification microscopy. To overcome the intrinsic limits of this method, contrast enhanced microtomographic (CE- microCT) protocols are constantly evolving to allow 3D study of soft tissues. However, no standardized approaches are available, and many concerns exist about the alterations induced to the samples. Method. microCT/histology protocols were explored on human tendons and menisci. To enhance contrast tissues for microCT scanning 1) examethyldisilazane drying 2) 2% phosphotungstic acid (PTA) in alcoholic solution exposition and 3) 2% PTA in aqueous solution exposition were performed; to observe PTA contrast progression, three exposition and scanning times were selected. microCT images were compared to histological slices obtained from the same samples, after rehydration protocols, or from adjacent tissues portion, stained with Picrosirius red to highlight the peculiar collagenic structures. Result. Exposition times influence PTA diffusion and tissue contrast; its specificity for collagenic structure allow a clearer contrast of the tissues. Histological processing on the same samples is possible: PTA removal requires careful washing in basic solution to reduce the hardening of the sample, while drying can be reverted applying inverse protocol. Comparison with microCT images is really accurate if histology is performed on the same sample, although all protocols induce tissue shrinkage with relative packing of collagen fibers. Conclusion. The contrast approaches tested proved effective in highlighting the structures of both tendons and menisci, but the structural effects induced by tissue shrinkage do not allow a completely real microCT visualization of native tissue. Histology can be the reference method to monitor the efficacy of the contrast methods and the alterations induced to define the possibility of improvement of the technique. Acknowledgement. PR23-PAS-P4 “ADJOINT 2”- INAIL


Aims

This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs).

Methods

A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1021 - 1030
1 Sep 2024
Oto J Herranz R Fuertes M Plana E Verger P Baixauli F Amaya JV Medina P

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Methods

We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 3 - 3
2 Jan 2024
Workineh Z Muñoz-Moya E Wills C Noailly J
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Intervertebral discs (IVD) provide flexibility to the back and ensure functional distributions of the spinal loads. They are avascular, and internal diffusion-dependent metabolic transport is vital to supply nutrients to disc cells1, but interactions with personalized IVD shapes and mechanics remain poorly explored. Poromechanical finite element models of seven personalized lumbar IVD geometries, with mean heights ranging from 8 to 16 mm were coupled with a reactive oxygen, glucose and lactate transport model linked with tissue deformations and osmosis . In previous studies, reduced formulations of the divergence of the solute flux (∇ .J = ∇ . (D∇ C) = ∇ D. ∇ C +D∇ 2C) ignored the dependence of the diffusion on the deformation gradients, ∇ D. ∇C. We simulated this phenomenon to explore its significance in mechano-metabolic -transport couplings, in the different geometries, over 24h of simulated rest (8h) and physical activity (16h). ∇ D. ∇ C affected the daily variations of glucose concentrations in IVD thinner than 12 mm but with neglectable variation ranges, while not considering ∇ D. ∇ C in taller discs only slightly overestimated the glucose concentration. Most importantly, tall IVD had nearly 60% less glucose than thin IVD, with local drops below the concentration of 0.5 mM, considered to be critical for disc cells3, in the anterior nucleus pulposus. On the one hand, previous reduced formulations for mechanometabolic-transport models of the IVD seem acceptable, even for patient-specific modelling. On the other hand, tall IVD might suffer from unfortunate combinations of deformation-dependent solute diffusion and large diffusion distances, which may favor early. Acknowledgements: Catalan Government and European Commission (2020 BP 00282; ERC-2021-CoG-O-Health-101044828)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 124 - 124
2 Jan 2024
Pascuet-Fontanet A Segarra-Queralt M Noailly J
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Osteoarthritis (OA) leads to articular cartilage degradation, following complex dysregulation of chondrocyte's metabolism towards a catabolic state. Mechanical and biochemical signals are involved and need to be considered to understand the condition. Regulatory network-based models (RNM) successfully simulated the biological activity of the chondrocyte and the transduction of mechanical signals at the molecular and cell levels. However, the knowledge gap between single-cell regulation and intercellular communication in tissue volumes hinders the interpretability of such models at larger scales. Accordingly, a novel tissue-level biochemical model is proposed. We hypothesise that it is possible to simulate interacting network effects through the transport of diluted species in a finite-element model, to grasp relevant dynamics of cell and tissue regulation in OA. Chondrocyte RNM equations were translated into a reaction term of 18 multi-species diffusion model (e.g., 3 anti-inflammatory and 8 pro-inflammatory interleukins, 3 pro-anabolic and 1 pro-catabolic growth factors, 2 nociceptive factors and 2 pro-inflammatory cytokines). Elements with RNM reaction terms represented the chondrocytes and were distributed randomly through the model, according to known cellular density in the knee cartilage, and could both react to and produce diffusive entities through the pericellular matrix, associated with reduced diffusion coefficients. The model was constructed over a 2D square of 0.47 mm sides considered to be in the middle of the cartilage, so boundary conditions were settled as periodic. Different simulations were initialised with initial concentrations of either healthy or pro-OA mediators. Preliminary results showed that, independently of the initial conditions, the chondrocytes successfully evolved into anabolic states, in absence of sustained pro-catabolic external stimulations, in contrast to single-cell RNM [2]. Our intercellular model suggests that paracrine communication may increase robustness towards cartilage maintenance, and future tests shall reveal new OA dynamics. Acknowledgements: Funding was provided by the European Commission (ERC-2021-CoG-O-Health-101044828)


Bone & Joint Research
Vol. 12, Issue 12 | Pages 712 - 721
4 Dec 2023
Dantas P Gonçalves SR Grenho A Mascarenhas V Martins J Tavares da Silva M Gonçalves SB Guimarães Consciência J

Aims

Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters.

Methods

We used the PRISMA extension for scoping reviews for this literature search in three databases. After screening, 16 studies were included for the final analysis.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 63 - 63
24 Nov 2023
Prebianchi SB Santos INM Brasil I Charf P Cunha CC Seriacopi LS Durigon TS Rebouças MA Pereira DLC Dell Aquila AM Salles M
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Aim. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is commonly associated with serious cases of community-onset skin and musculoskeletal infections (Co-SMSI). Molecular epidemiology analysis of CA-MRSA recovered from skin and soft tissues specimens is lacking in Latin America. This study aimed to identify phenotypic and genotypic features of MRSA isolates recovered from patients presenting Co-SMSI. Methods. Consecutive MRSA isolates recovered from Co-SMSI of patients admitted from March 2022 to January 2023 in a Brazilian teaching hospital were tested for antimicrobial resistance and characterized by their genotypic features. Identification was carried out by automated method and through MALDI-TOF MS. Antimicrobial susceptibility was tested by disk diffusion, broth microdilution and E-test strips for determination of the minimal inhibitory concentration (MIC) according to recommendations from the Brazilian Committee on Antimicrobial Susceptibility Testing (BrCAST) and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Gene mecA characterization and Sccmec typing were performed by multiplex polymerase chain reaction (PCR) assay, and gene lukF detection by single PCR. Patients were prospectively followed up for two months, in order to determine their clinical characteristics and outcomes. Results. Overall, 48 Staphylococcus aureus isolates were obtained from 68 samples recovered from patients with Co-SMSI. Twenty two (42%) were phenotypically characterized as MRSA, although mecA gene was only identified in 20 of those samples. Sccmec was untypable in 12 isolates, Sccmec was type II in 4 isolates and 2 were classified as type IVa. LukF gene was identified in 5 isolates. Antimicrobial resistance profile showed that all isolates were susceptible to linezolid and vancomycin with MIC = 1 and MIC = 2 in 66,7% and 33.3%, respectively. Susceptibility to quinolones was worryingly low and none of the isolates were sensitive to usual doses of ciprofloxacin and levofloxacin, and showed increased rates of resistance to increased exposure to these drugs, as well. Isolates were both susceptible to gentamicin and tetracycline in 85% and resistance to also Sulfamethoxazole/Trimethoprim occurred in only 2 isolates. Mortality rate evaluated within 1 month of the initial evaluation was 10% among MRSA isolates. Conclusions. Our results showed that CA-MRSA isolates causing Co-SMSI demonstrated an alarming pattern of multidrug resistance, including to β-lactam and quinolones, which have been commonly prescribed as empirical therapy for patients with skin, soft tissue and musculoskeletal infections


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 6 - 6
24 Nov 2023
Soares F Santos INM Seriacopi LS Durigon TS Cunha CC Dell Aquila AM Salles M
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Aim. Currently, gram-negative bacteria (GNB), including multidrug-resistant (MDR-GNB) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). To characterize the antimicrobial resistance patterns of Gram-negative bacteria (GNB) causing hip prosthetic joint infections in elderly patients treated at a Brazilian tertiary academic hospital. Method. This is a retrospective, cross-sectional study of patients over 60 years of age undergoing hip arthroplasty from 2018 to 2023 at a tertiary academic trauma, which were diagnosed with hip prosthetic joint infection. PJI diagnosed was based on EBJIS criteria, in which intraoperative tissue cultures identified the pathogens. Demographics, reason for arthroplasty, type of implant and susceptibility patterns using disk diffusion method were analysed. Results. Overall, among 17 elderly patients diagnosed with hip infected arthroplasty, 45 bacterial isolated were identified. Debridement, irrigation, antibiotic and implant retention (DAIR) procedures due to uncontrolled infection occurred in 47.0% (n=8/17), and five patients underwent more than two DAIR surgeries. Tissue cultures yielded eleven different bacterial species, with GNB accounted for 64.4% (n=29/45) of pathogens. Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa were identified in 34.5% (n=10/29), 17.25% (n=5/29), 13.8% (n=4/29), and 13.8% (n=4/29), respectively. In the resistance profile analysis, E. coli was most sensitive to antibiotics, whereas K. pneumoniae showed resistance rates higher than 70% for cephalosporins, carbapenems, and quinolones. All A. baumannii isolates were resistant to meropenem, and 80% of these isolates were resistant to amikacin. Conclusions. This study emphasizes the role of GNB in the microbiological profile of PJI among elderly patients at a tertiary hospital in a Brazilian centre. The present study portrays a worryingly higher rates of MDR-GNB, mainly to quinolones and cephalosporins resistance which have been the cornerstone of PJI antibiotic treatment. In addition, higher rates carbapenems and aminoglycosides resistance shows a threat to antibiotic treatment of PJI. More global studies need to be carried out to show a likely change in the microbial epidemiology of PJI


Bone & Joint 360
Vol. 12, Issue 5 | Pages 3 - 4
1 Oct 2023
Ollivere B


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 41 - 41
11 Apr 2023
Deegan A Lawlor L Yang X Yang Y
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Our previous research has demonstrated that minor adjustments to in vitro cellular aggregation parameters, i.e. alterations to aggregate size, can influence temporal and spatial mineral depositions within maturing bone cell nodules. What remains unclear, however, is how aggregate size might affect mineralisation within said nodules over long-term in vivo culture. In this study, we used an osteoblast cell line, MLO-A5, and a primary cell culture, mesenchymal stem cells (MSC), to compare small (approximately 80 µm) with large (approximately 220 µm) cellular aggregates for potential bone nodule development after 8 weeks of culturing in a mouse model (n = 4 each group). In total, 30 chambers were implanted into the intra-peritoneal cavity of 20 male, immunocompromised mice (MF1-Nu/Nu, 4 – 5 weeks old). Nine small or three large aggregates were used per chamber. Neoveil mesh was seeded directly with 2 × 10. 3. cells for monolayer control. At 8 weeks, the animals were euthanised and chambers fixed with formalin. Aggregate integrity and extracellular material growth were assessed via light microscopy and the potential mineralisation was assessed via micro-CT. Many large aggregates appeared to disintegrate, whilst the small aggregates maintained their form and produced additional extracellular material with increased sizes. Both MLO-A5 cells and MSC cells saw similar results. Interestingly, however, the MSCs were also seen to produce a significantly higher volume of dense material compared to the MLO-A5 cells from micro-CT analysis. Overall, a critical cell aggregate size appeared to exist balancing optimal tissue growth with oxygen diffusion, and cell source may influence differentiation pathway despite similar experimental parameters. The MSCs, for example, were likely producing bone via the endochondral ossification pathway, whilst the matured bone cells, MLO-A5 cells, were likely producing bone via the intramembranous ossification pathway


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 36 - 36
11 Apr 2023
Boyce S Le Maitre C Smith T Nichol T
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An increasing elderly population means joint replacement surgery numbers are projected to increase, with associated complications such as periprosthetic joint infections (PJI) also rising. PJI are particularly challenging due to antimicrobial resistant biofilm development on implant surfaces and surrounding tissues, with treatment typically involving invasive surgeries and systemic antibiotic delivery. Consequently, functionalisation of implant surfaces to prevent biofilm formation is a major research focus. This study characterises clinically relevant antimicrobials including gentamicin, clindamycin, daptomycin, vancomycin and caspofungin within a silica-based, biodegradable sol-gel coating for prosthetic devices. Antimicrobial activity of the coatings against clinically relevant microorganisms was assessed via disc diffusion assays, broth microdilution culture methods and the MBEC assay used to determine anti-biofilm activity. Human and bovine cells were cultured in presence of antimicrobial sol-gel to determine cytotoxicity using Alamar blue and antibiotic release was measured by LC-MS. Biodegradability in physiological conditions was assayed by FT-IR, ICP-MS and measuring mass change. Effect of degradation products on osteogenesis were studied by culturing mesenchymal stem cells in the presence of media in which sol-gel samples had been immersed. Antimicrobial-loaded coatings showed strong activity against a wide range of clinically relevant bacterial and fungal pathogens with no loss of activity from antibiotic alone. The sol-gel coating demonstrated controlled release of antimicrobials and initial sol-gel coatings showed no loss of viability on MSCs with gentamicin containing coatings. Current work is underway investigating cytotoxicity of sol-gel compositions against MG-63 cells and primary osteoblasts. This research forms part of an extended study into a promising antimicrobial delivery strategy to prevent PJI. The implant coating has potential to advance PJI infection prevention, reducing future burden upon healthcare costs and patient wellbeing


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 113 - 113
11 Apr 2023
de Mesy Bentley K Galloway C Muthukrishnan G Masters E Zeiter S Schwarz E Leckenby J
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Serial section electron microscopy (SSEM) was initially developed to map the neural connections in the brain. SSEM eventually led to the term ‘Connectomics’ to be coined to describe process of following a cell or structure through a volume of tissue. This permits the true three-dimensionality to be appreciated and relationships between cells and structures. The purpose of this study was to utilize this methodology to interrogate S. aureus infected bone. Bone samples were harvested from mice tibia infected with S. aureus and were fixed, decalcified, and osmicated. The samples were paraffin embedded and 5-micron sections were cut to identify regions of bacterial invasion into the osteocyte-lacuna-canalicular-network (OLCN). This area was cut from the paraffin block, deparaffinized, post-fixed and reprocessed into epoxy resin. Serial sections were cut at 60nm and collected onto Kapton tape utilizing the Automated Tape-collecting Ultramicrotome (ATUMtome) system. Samples were mounted onto 4” silicon wafers and post-stained with 2% uranyl acetate followed by 0.3% lead citrate and carbon coated. A ZEISS GeminiSEM 450 scanning electron microscope fitted with an electron backscatter diffusion detector was used to image the sections. The image stack was aligned and segmented using the open-source software, VASTlite. 264 serial sections were imaged, representing approximately 40 × 45 × 15-micron (x, y, z) volume of tissue. 70% of the canaliculi demonstrated infiltration by S. aureus. This study demonstrates that SSEM can be applied to the skeletal system and provide a new solution to investigate the OLCN system. It is feasible that this methodology could be implemented to investigate why some canaliculi are resistant to colonization and potentially opens up a new direction for the prevention of chronic osteomyelitis. In order to make this a realistic target, automated segmentation methodologies utilizing machine learning must be developed and applied to the bone tissue datasets


Bone & Joint 360
Vol. 12, Issue 2 | Pages 6 - 9
1 Apr 2023
O’Callaghan J Afolayan J Ochieng D Rocos B


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_2 | Pages 3 - 3
10 Feb 2023
Sundaram A Woods J Clifton L Alt V Clark R Carey Smith R
Full Access

Complex acetabular reconstruction for oncology and bone loss are challenging for surgeons due to their often hostile biological and mechanical environments. Titrating concentrations of silver ions on implants and alternative modes of delivery allow surgeons to exploit anti-infective properties without compromising bone on growth and thus providing a long-term stable fixation. We present a case series of 12 custom acetabular tri-flange and custom hemipelvis reconstructions (Ossis, Christchurch, New Zealand), with an ultrathin plasma coating of silver particles embedded between layers of siloxane (BioGate HyProtect™, Nuremberg, Germany). At the time of reporting no implant has been revised and no patient has required a hospital admission or debridement for a deep surgical site infection. Routine follow up x-rays were reviewed and found 2 cases with loosening, both at their respective anterior fixation. Radiographs of both cases show remodelling at the ilium indicative of stable fixation posteriorly. Both patients remain asymptomatic. 3 patients were readmitted for dislocations, 1 of whom had 5 dislocations within 3 weeks post-operatively and was immobilised in an abduction brace to address a lack of muscle tone and has not had a revision of their components. Utilising navigation with meticulous implant design and construction; augmented with an ultrathin plasma coating of silver particles embedded between layers of siloxane with controlled and long-term generation of silver ion diffusion has led to outstanding outcomes in this series of 12 custom acetabular and hemipelvis reconstructions. No patients were revised for infection and no patients show signs of failure of bone on growth and incorporation. Hip instability remains a problem in these challenging mechanical environments and we continue to reassess our approach to this multifaceted problem


The Bone & Joint Journal
Vol. 105-B, Issue 1 | Pages 11 - 16
1 Jan 2023
San-Julián M Gómez-Álvarez J Idoate MÁ Aquerreta JD Vázquez-García B Lamo-Espinosa JM

Paediatric bone sarcomas are a dual challenge for orthopaedic surgeons in terms of tumour resection and reconstruction, as it is important to minimize functional and growth problems without compromising survival rates. Cañadell’s technique consists of a Type I epiphysiolysis performed using continuous distraction by an external fixator prior to resection. It was designed to achieve a safe margin due to the ability of the physeal cartilage to be a barrier to tumour spread in some situations, avoiding the need for articular reconstruction, and preserving the growth capacity most of the times. Despite initial doubts raised in the scientific community, this technique is now widely used in many countries for the treatment of metaphyseal paediatric bone sarcomas. This annotation highlights the importance of Cañadell’s work and reviews the experience of applying it to bone sarcoma patients over the last 40 years.

Cite this article: Bone Joint J 2023;105-B(1):11–16.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 57 - 57
1 Dec 2022
Champagne A McGuire A Shearer K Brien D Martineau PA Bardana DD
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Reconstruction of the anterior cruciate ligament (ACL) allows to restore stability of the knee, in order to facilitate the return to activity (RTA). Although it is understood that the tendon autograft undergoes a ligamentous transformation postoperatively, knowledge about longitudinal microstructural differences in tissue integrity between types of tendon autografts (ie, hamstring vs. patella) remains limited. Diffusion tensor imaging (DTI) has emerged as an objective biomarker to characterize the ligamentization process of the tendon autograft following surgical reconstruction. One major limitation to its use is the need for a pre-injury baseline MRI to compare recovery of the graft, and inform RTA. Here, we explore the relationship for DTI biomarkers (fractional anisotropy, FA) between knees bilaterally, in healthy participants, with the hypothesis that agreement within a patient's knees may support the use of the contralateral knee as a reference to monitor recovery of the tendon autograft, and inform RTA. Fifteen participants with no previous history of knee injuries were enrolled in this study (age, 26.7 +/− 4.4 years; M/F, 7/8). All images were acquired on a 3T Prisma Siemens scanner using a secured flexible 18-channel coil wrapped around the knee. Both knees were scanned. A 3D anatomical Double Echo Steady State (DESS) sequence was acquired on which regions of interest (ROI) were placed consistent with the footprints of the ACL (femur, posteromedial corner on medial aspect of lateral condyle; tibia, anteromedial to intercondylar eminence). Diffusion images were acquired using fat saturation based on optimized parameters in-house. All diffusion images were pre-processed using the FMRIB FSL toolbox. The footprint ROIs of the ACL were then used to reconstruct the ligament in each patient with fiber-based probabilistic tractography (FBPT), providing a semi-automated approach for segmentation. Average FA was computed for each subject, in both knees, and then correlated against one another using a Pearson correlation to assess the degree of similarity between the ACLs. A total of 30 datasets were collected for this study (1/knee/participant; N=15). The group averaged FA (+/− standard deviation) for the FBPT segmented ACLs were found to equal 0.1683 +/− 0.0235 (dominant leg) and 0.1666 +/− 0.0225 (non-dominant leg). When comparing both knees within subjects, reliable agreement was found for the FBPT-derived ACL with a linear correlation coefficient (rho) equal to 0.87 (P < 0 .001). We sought to assess the degree of concordance in FA between the knees of healthy participants with hopes to provide a method for using the contralateral “healthy” knee in the comparison of autograft-dependent longitudinal changes in microstructural integrity, following ACL reconstruction. Our results suggest that good agreement in anisotropy can be achieved between the non-dominant and dominant knees using DTI and the FBPT segmentation method. Contralateral anisotropy of the ACL, assuming no previous injuries, may be used as a quantitative reference biomarker for monitoring the recovery of the tendon autograft following surgical reconstruction, and gather further insight as to potential differences between chosen autografts. Clinically, this may also serve as an index to supplement decision-making with respect to RTA, and reduce rates of re-injuries


Bone & Joint Research
Vol. 11, Issue 12 | Pages 862 - 872
1 Dec 2022
Wang M Tan G Jiang H Liu A Wu R Li J Sun Z Lv Z Sun W Shi D

Aims

Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA.

Methods

We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs.


Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L

Aims. There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). Methods. The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites. Results. Following the addition of RIF to CaS/HA-VAN/GEN, adequate injectability and setting of the CaS/HA composites were noted. Sustained release of RIF above the minimum inhibitory concentrations of S. aureus was observed until study endpoint (day 35). Only combinations of CaS/HA-VAN/GEN + RIF exhibited antibacterial and antibiofilm effects yielding no viable bacteria at study endpoint. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with CaS/HA-VAN/GEN + RIF. Conclusion. Our in vitro results indicate that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for local delivery in clinically demanding bone infections. Cite this article: Bone Joint Res 2022;11(11):787–802


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 32 - 32
1 Oct 2022
Tøstesen S Stilling M Hanberg P Thillemann TM Falstie-Jensen T Tøttrup M Knudsen M Petersen ET Bue M
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Aim. Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). Method. In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected from a central venous catheter as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus (fT > MIC (4 µg/mL)). Results. During the two dosing intervals, mean fT > MIC (4 µg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 µg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. Conclusions. In conclusion, weight-adjusted cefuroxime fT > MIC (4 µg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI. Acknowledgments. We would like to thank Department of Clinical Medicine, the surgical research laboratories, Aarhus University Hospital and Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Denmark, for supporting this study. This research was funded by Novo Nordisk Foundation, grant number [NNF20OC0062032, 2020]


Bone & Joint Research
Vol. 11, Issue 8 | Pages 548 - 560
17 Aug 2022
Yuan W Yang M Zhu Y

Aims

We aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.

Methods

Five datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.