Introduction. Instability in ACL deficient knees can lead to medial compartment osteoarthritis. The risk of developing significant OA is 5x higher in knees with ACL deficiency. In associated Varus, there is quicker progression of the medial OA along with a varus thrust exerting strain on the ACL graft. The simultaneous valgus HTO and ACL reconstruction decompresses the medial tibiofemoral joint, corrects the mechanical-axis and reduces strain on the graft. Outcomes for this simultaneous procedure are still unclear in literature and we attempt evaluating its functional outcome. Methods. This Panel study was performed using data from 2019 to 2022 on 21 patients who had ACL insufficiency with Varus or medial OA and underwent a simultaneous Opening-wedge HTO with Arthroscopic ACL reconstruction. The mean follow-up was 2 years. The patients were evaluated with IKDC and Lysholm scores, Lachman test and ROM pre and post-operatively. The HKA was compared pre and post-operatively and the complications were evaluated. The progression of OA was evaluated with serial radiographs post-operatively. Results. There was a significant improvement in lifestyle and knee joint function post-operatively. The mechanical femorotibial angle was corrected from an average of 8.2° Varus to 0.8° Valgus. There was a significant improvement in IKDC and Lysholm scoring (IKDC score improved to 86.20 from 34.48 and the Lysholm score improved to 89 points from 37 points). There was significant improvement in the laxity which was evaluated by Lachman test. One patient had a clinical progression of medial-OA. No patients had non-union, graft or implant failure. Conclusion. Single stage HTO and ACL Reconstruction in patients with medial OA or Varus with ACL insufficiency is an option showing a satisfactory functional and radiological outcome along with activity scores

Aims

This cross-sectional study aimed to investigate the in vivo ankle kinetic alterations in patients with concomitant chronic ankle instability (CAI) and osteochondral lesion of the talus (OLT), which may offer opportunities for clinician intervention in treatment and rehabilitation.

Aims

Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

Aims

Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting.

The December 2024 Oncology Roundup³⁶⁰ looks at: Non-reversed great saphenous vein grafts for vascular reconstruction after resection of lower limb sarcoma; Detrimental effects of COVID-19 pandemic on patients with limb bone sarcoma: reference centre experience; Whole-body staging guidelines in sarcoma; Intraoperative marrow margin frozen section in limb bone sarcoma resection; Vacuum-assisted closure and paediatric oncological limb salvage; Treatment differences and long-term outcomes in adults and children with Ewing’s sarcoma; Survival, complications, and functional outcomes of uncemented distal femoral endoprosthesis with short, curved stem for patients with bone tumours.

Aim. Orthopedic implants play a tremendous role in fixing bone damages due to aging as well as fractures. However, these implants tend to get colonized by bacteria on the surface, leading to infections and subsequently prevention of healing and osteointegration. Recently, Roupie et al. showed that a nisin layer-by-layer based coating applied on biomaterials has both osteogenic and antibacterial properties. The Galleria mellonella larva is a well-known insect infection model that has been used to test the virulence of bacterial and fungal strains as well as for the high throughput screening of antimicrobial compounds against infections. Recently, we have developed an insect infection model with G. mellonella larvae to study implant-associated biofilm infections using Kirschner (K)-wires as implant material. Here, we would like to test the antibacterial capacity of nisin layer-by-layer based coatings on K-wires against Staphylococcus aureus in the G. mellonella larva implant infection model. Method. Prior to the implantation procedure, G. mellonella larvae are maintained at room temperature on wheat germ in an incubator. The larvae received bare titanium K-wires (uncoated), or either control-coated or nisin-coated K-wires. After one hour, the larvae were injected with 5×10. 5. S. aureus bacteria per larva (i.e., hematogenous implant infection model). Next, the larvae were incubated at 37. o. C in an incubator and the survival of the larvae was monitored for five days. Moreover, the number of bacteria on the implant surface and in the surrounding tissue was determined after 24h of incubation. Further, scanning electron microscopy (SEM) analyses were performed to study the effect of nisin on biofilm formation. Results. The larvae receiving the nisin-coated K-wires showed significantly higher survival rates compared to uncoated titanium K-wires, although not when compared to control-coated K-wires. A more than 1-log reduction in number of bacteria on the implant surface and in the surrounding tissue was observed in larvae receiving the nisin-coated K-wires, when compared to uncoated titanium K-wires SEM analysis showed reduced colonization of the bacteria nisin-coated K-wires compared to the controls. Conclusions. In conclusion, the antimicrobial nisin layer-by-layer based coating applied on titanium surfaces is able to prevent implant-related S. aureus biofilm infection in G. mellonella and is a promising antimicrobial strategy to prevent implant-related infections

Aim. Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1). Method. Methicillin-resistant Staphylococcus aureus (MRSA) biofilm was grown on porous glass beads for 24 h in vitro. After the biofilm formation, beads were exposed to 0.9% saline, then sonication. Quantitative and qualitative biofilm analyses were performed by colony counting, scanning electron microscopy and isothermal microcalorimetry. A rat model of total knee arthroplasty infected with the bioluminescent MRSA strain was developed as the PJI model to evaluate the efficacy of Lip-RIF@Phage anti-biofilm therapy in vivo, then the creatinine, alanine transaminase, and aspartate transaminase values were evaluated throughout the entire treatment process. Results. After treatment with Lip-RIF@Phage, no bacterial colonies were observed, consistent with findings from scanning electron microscopy. Similarly, isothermal microcalorimetry revealed no detectable heat following Lip-RIF@Phage treatment, aligning with these observations. In vivo experiments demonstrated a significant reduction in biofilm cell load compared to all other tested conditions, with no evidence of systemic toxicity on renal and liver functions attributed to Lip-RIF@Phage. Conclusions. The innovative depolymerase-phagobot nanosystem (Lip-RIF@Phage) exhibits remarkable efficacy in completely eliminating biofilm cells in vitro. It serves as an excellent carrier for antibiotic delivery, enhancing antibiotic penetration through biofilms and improving biofilm eradication efficacy. Furthermore, it enables personalized treatment strategies against biofilm-associated multidrug-resistant (MDR) infections by maximizing the effectiveness of any remaining sensitive antibiotics. For any tables or figures, please contact the authors directly

Aim. The aim of this study was to develop an in-house multiplex PCR real-time assay on the LightCycler 480 system (Roche, Basel, Switzerland) with the aim of rapid detection of common pathogens in prosthetic joint infections (PJI), followed by validation on clinical samples (sonication fluid and tissue biopsies) routinely collected for PJI diagnosis. Methods. Using the PrimerQuest and CLC WorkBench tool, we designed six primer sets with specific fluorescently labelled TaqMan probes for the nuc gene in different Staphylococcus species (S. aureus, S. epidermidis, S. capitis, S. lugdunensis, S. hominis, S. haemolyticus). In addition, primers previously developed by Renz et al. (2022) for C. acnes were integrated into our assay with internal control of isolation, leading to the development of specific mPCR assay with seven included targets. Analytical sensitivity and specificity were evaluated using reference bacterial strains. To determine the assay's limit of detection (LOD), we conducted serial dilutions of eluates containing known concentrations of bacterial DNA copies/µl. The overall LOD in spiked clinical samples, including sample preparation and DNA isolation on MagnaPure24, was measured through 10-fold serial dilutions (from 10. 9. to 10. -1. CFU/ml) including additional dilutions of 5000, 500, 50 and 5 CFU/ml. Results. The results with LOD in serial dilutions of eluates and spiked clinical samples, together with analytical sensitivity and specificity, are shown in Table 1. Conclusion. The mPCR assay showed excellent analytical sensitivity and specificity, but with considerably lower LOD after sample preparation and further DNA isolation in spiked clinical samples. Although still promising in diagnostics of acute infections, the use of mPCR could be challenging in chronic, low-grade infections with lower microbial burden. Nevertheless, PCR offers significant advantages in terms of speed and can shorten the time to result, especially for C. acnes infections. Additionally, it represents a promising complementary approach in patients with suspected PJI on antibiotic therapy with negative culture results. For any tables or figures, please contact the authors directly

Introduction. In specific conditions, infection may lead to bone loss and is difficult to treat. 1. Current clinical approaches rely on the introduction of antibiotics. While these may be effective, there are concerns regarding the rise of antimicrobial resistance. There is therefore interest in the development of antimicrobial bone graft substitutes for dental and trauma surgery. Aim & Objectives. The incorporation of zinc into biomaterials has been shown to confer broad spectrum antimicrobial activity, but this has not yet been applied to the development of a commercial bone graft substitute. The aim of this research was therefore to prepare and characterise a series of zinc-substituted nanoscale hydroxyapatite (nHA) materials, including evaluation of antimicrobial activity. Method. Zinc (Zn) substituted nHA materials were prepared (0, 5, 10, 15 & 20 mol.% Zn) using a wet chemical precipitation method with a rapid mixing. (2). The reaction was carried out using zinc hydroxide at pH 10. The suspension formed was washed and dried into both powder & paste forms. The resultant powders were characterized using transmission electron microscopy (TEM) and X-ray diffraction (XRD). The antimicrobial activity was evaluated against Staphylococcus aureus (S8650 strain - isolated from an osteomyelitis case), by two techniques. The Miles and Misra method was applied to determine the number of colony-forming units (CFUs) in bacterial suspensions incubated with pastes. Secondly, a biofilm initialization method was used to evaluate the capacity of the materials to prevent biofilm formation. One-way analysis of variance (ANOVA) was used for the statistical analysis and results with p-value < 0.05 were considered statistically significant. Results. XRD indicated the formation of pure hydroxyapatite with up to 10 mol.% Zn without any side products. However, when Zn was increased to 15 & 20 mol %, zinc oxide (ZnO) peaks were detected. The TEM showed nanoscale needle-like particles when Zn was increased compared to nHA particles. Regarding the antibacterial activity, ZnHA pastes at all concentrations caused a significant reduction in bacterial CFUs in a dose-dependent manner (50, 100 & 200 mg). Additionally, even the lowest zinc substitution (5 mol.%) significantly reduced biofilm formation. Conclusion. The results demonstrated a novel method to produce a Zn-substituted nHA that showed antimicrobial activity against a pathogen isolated from a bone infection

Aim. In trauma surgery, the development of biomaterial-associated infections (BAI) is one of the most common complications affecting trauma patients, requiring prolonged hospitalization and the intensive use of antibiotics. Following the attachment of bacteria on the surface of the biomaterial, the biofilm-forming bacteria could initiate a chronic implant-related infection. Despite the use of conventional local and systemic antibiotic therapies, persistent biofilms involve various resistance mechanisms that contribute to therapeutic failures. The development of in vivo chronic BAI models to optimize antibiofilm treatments is a major challenge. Indeed, the biofilm pathogenicity and the host response need to be finely regulated, and compatible with the animal lifestyle. Previously, a Galleria mellonella larvae model for the formation of an early-stage biofilm on the surface of a Kirschner (K)-wire was established. In the present study, two models of mature biofilm using clinical Staphylococcus aureus strains were assessed: one related to contaminated K-wires (in vitro biofilm maturation) and the second to hematogenous infections (in vivo biofilm maturation). Rifampicin was used as a standard drug for antibiofilm treatment. Method. In the first model, biofilms were formed following an incubation period (up to 7 days) in the CDC Biofilm Reactor (CBR, BioSurface Technologies). Then, after implantation of the pre-incubated K-wire in the larvae, rifampicin (80 mg/kg) was injected and the survival of the larvae was monitored. In the second model, biofilm formation was achieved after an incubation period (up to 7 days) inside the larvae and then, after removing the K-wires from the host, in vitro rifampicin susceptibility assays were performed (according to EUCAST). Results. The first model indicate that in vitro biofilm maturation affects the bacterial pathogenicity in the host, depending on the S. aureus strain used. Furthermore, the more the biofilm is matured, the more the rifampicin treatment efficiency is compromised. The second model shows that, despite the fast in vivo biofilm formation in the host, the number of bacteria, either attached to the surface of the K-wire surface or in surrounding tissue of the larvae, was not increased over time. Conclusions. Altogether, these results allow the establishment of biofilm models using G. mellonella larvae in order to understand the impact of biofilm maturation on both the bacterial pathogenicity and the efficiency of antibiofilm treatments

Introduction. This study aimed to evaluate the effectiveness of a novel intraoperative navigation platform for total knee arthroplasty (TKA) in restoring native knee joint kinematics and strains in the medial collateral ligament (MCL) and lateral collateral ligament (LCL) during squatting motions. Method. Six cadaver lower limbs underwent computed tomography scans to design patient-specific guides. Using these scans, bony landmarks and virtual single-line collateral ligaments were identified to provide intraoperative real-time feedback, aided in bone resection, implant alignment, tibiofemoral kinematics, and collateral ligament elongations, using the navigation platform. The specimens were subjected to squatting (35°-100°) motions on a physiological ex vivo knee simulator, maintaining a constant 110N vertical ankle load regulated by active quadriceps and bilateral hamstring actuators. Subsequently, each knee underwent a medially-stabilized TKA using the mechanical alignment technique, followed by a retest under the same conditions used preoperatively. Using a dedicated wand, MCL and LCL insertions—anterior, middle, and posterior bundles—were identified in relation to bone-pin markers. The knee kinematics and collateral ligament strains were analyzed from 3D marker trajectories captured by a six-camera optical system. Result. Both native and TKA conditions demonstrated similar patterns in tibial valgus orientation (Root Mean Square Error (RMSE=1.7°), patellar flexion (RMSE=1.2°), abduction (RMSE=0.5°), and rotation (RMSE=0.4°) during squatting (p>0.13). However, a significant difference was found in tibial internal rotation between 35° and 61° (p<0.045, RMSE=3.3°). MCL strains in anterior (RMSE=1.5%), middle (RMSE=0.8%), and posterior (RMSE=0.8%) bundles closely matched in both conditions, showing no statistical differences (p>0.05). Conversely, LCL strain across all bundles (RMSE<4.6%) exhibited significant differences from mid to deep flexion (p<0.048). Conclusion. The novel intraoperative navigation platform not only aims to achieve planned knee alignment but also assists in restoring native knee kinematics and collateral ligament behavior through real-time feedback. Acknowledgment. This study was funded by Medacta International (Castel San Pietro, Switzerland)

Introduction. Bone and joint infection (BJI) is often characterized by severe inflammation and progressive bone destruction. Osteocytes are the most numerous and long-lived bone cell type, and therefore represent a potentially important long-term reservoir of bacterial infection. Staphylococcus aureus is known to establish stable intracellular osteocytic infections, however, little is known about the less virulent yet second most prevalent BJI pathogen, S. epidermidis, associated with late-diagnosed, chronic BJI. Thus, this study sought to establish an in vitro model to study the infection characteristics of S. epidermidis in human osteocyte-like cells. Methods. SaOS2 cells (1 ×10. 4. cells/cm. 2. ) were grown to confluence either without differentiation, representing an osteoblast-like (OB) state (SaOS2-OB) or differentiated to an osteocyte-like stage (SaOS2-OY), using established methods. Four S. epidermidis strains used (ATCC-12228, ATCC-14990, ATCC-35984 and a clinical osteomyelitis strain RAH-SE1) were tested to be Lysostaphin-resistant, necessitating antibiotic (Levofloxacin) control of extracellular bacteria. Infection of host cells (OB or OY) was tested at three multiplicities of infection (MOI: 10, 100 and 1000). Extracellular bacteria were controlled by overnight incubation at a 10X minimum inhibitory concentration (MIC) of Levofloxacin and thereafter at 1XMIC. At each time point (days 1, 3, 5) viable intra- and extracellular bacteria were quantified. Result. All strains displayed similar intracellular infection and persistence capabilities in SaOS2-OB and SaOS2-OY. Independent of MOI, intracellular bacteria in SaOS2-OB decreased over time, becoming non-culturable by day 5. In contrast, SaOs2-OY displayed enhanced intracellular bacterial persistence at each time point. In the presence of increased Levofloxacin concentration (10XMIC), S. epidermidis could persist intracellularly for at least 14 days. Conclusion. This study showed for the first time that S. epidermidis can infect human osteocytes and persist intracellularly. Additionally, even a 10xMIC antibiotic concentration failed to eradicate intracellular bacteria, suggesting that persistence within osteocytes could contribute to treatment failure and establishment of chronic BJI

Introduction. Transosseous flexion-distraction injuries of the spine typically require surgical intervention by stabilizing the fractured vertebra during healing with a pedicle-screw-rod constructs. As healing is taking place the load shifts from the implant back to the spine. Monitoring the load-induced deflection of the rods over time would allow quantifiable postoperative assessment of healing progress without the need for radiation exposure or frequent hospital visits. This approach, previously demonstrated to be effective in assessing fracture healing in long bones and monitoring posterolateral spinal fusion in sheep, is now being investigated for its potential in evaluating lumbar vertebra transosseous fracture healing. Method. Six human cadaveric spines were instrumented with pedicle-screws and rods spanning L3 vertebra. The spine was loaded in Flexion-Extension (FE), Lateral-Bending (LB) and Axial-Rotation (AR) with an intact L3 vertebra (representing a healed vertebra) and after transosseous disruption, creating an AO type B1 fracture. The implant load on the rod was measured using an implantable strain sensor (Monitor) on one rod and on the contralateral rod by a strain gauge to validate the Monitor's measurements. In parallel the range of motion (ROM) was assessed. Result. The ROM increased significantly in all directions in the fractured model (p≤0.049). The Monitor measured a significant increase in implant load in FE (p=0.002) and LB (p=0.045), however, not in AR. The strain gauge detected an increased implant load not only in FE (p=0.001) and LB (p=0.016), but also in AR (p=0.047). The highest strain signal was found during LB for both, the Monitor, and the strain gauge. Conclusion. After a complete transosseous disruption of L3 vertebra the load on the implants was significantly higher than in the intact respectively healed state. Innovative implantable sensors could be used to monitor those changes allowing the assessment of healing progression based on quantifiable data rather than CT-imaging

Introduction. In daily clinical practice, progression of spinal fusion is typically monitored during clinical follow-up using conventional radiography and Computed Tomography scans. However, recent research has demonstrated the potential of implant load monitoring to assess posterolateral spinal fusion in an in-vivo sheep model. The question arises to whether such a strain sensing system could be used to monitor bone fusion following lumbar interbody fusion surgery, where the intervertebral space is supported by a cage. Therefore, the aim of this study was to test human cadaveric lumbar spines in two states: after a transforaminal lumbar interbody fusion (TLIF) procedure combined with a pedicle-screw-rod-construct (PSR) and subsequently after simulating bone fusion. The study hypothesized that the load on the posterior instrumentation decreases as the segment stiffens due to simulated fusion. Method. A TLIF procedure with PSR was performed on eight human cadaveric spines at level L4-L5. Strain sensors were attached bilaterally to the rods to derive implant load changes during unconstrained flexion-extension (FE), lateral bending (LB) and axial rotation (AR) loads up to ±7.5Nm. The specimens were retested after simulating bone fusion between vertebrae L4-L5. In addition, the range of motion (ROM) was measured during each loading mode. Result. The ROM decreased in the simulated bone fusion state in all loading directions (p≤0.002). In both states, the measured strain on the posterior instrumentation was highest during LB motion. Furthermore, the sensors detected a significant decrease in the load induced rod strain (p≤0.002) between TLIF+PSR and simulated bone fusion state in LB. Conclusion. Implant load measured via rod strain sensors can be used to monitor the progression of fusion after a TLIF procedure when measured during LB of the lumbar spine. However, further research is needed to investigate the influence of daily loading scenarios expected in-vivo on the overall change in implant load

Aims

The aim of this study was to compare patient-reported outcomes (PROMs) following isolated anterior cruciate ligament reconstruction (ACLR), with those following ACLR and concomitant meniscal resection or repair.

Aims. The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against Staphylococcus aureus. Methods. We performed in vitro growth and viability assays to determine the capability of S. aureus to survive in SF with the addition of 10 µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated its sensitivity to killing, comparing wild type (WT) and CopAZB-deficient USA300 strains. Results. UAMS-1 demonstrated a greater sensitivity to SF compared to USA300 WT at 12 hours (p = 0.001) and 24 hours (p = 0.027). UAMS-1 died in statistically significant quantities at 24 hours (p = 0.017), and USA300 WT survived at 24 hours. UAMS-1 was more susceptible to the addition of copper at four (p = 0.001), 12 (p = 0.005), and 24 hours (p = 0.006). We confirmed a high sensitivity to killing with the addition of exogenous copper on both strains at four (p = 0.011), 12 (p = 0.011), and 24 hours (p = 0.011). WT and CopAZB-deficient USA300 strains significantly died in SF, demonstrating a MBC-Cu of 50 µM against USA300 WT (p = 0.011). Conclusion. SF has antimicrobial properties against S. aureus, and UAMS-1 was more sensitive than USA300 WT. Adding 10 µM of copper was highly toxic, confirming its bactericidal effect. We found CopAZB proteins to be involved in copper effluxion by demonstrating the high sensitivity of mutant strains to lower copper concentrations. Thus, we propose CopAZB proteins as potential targets and use exogenous copper as a treatment alternative against S. aureus. Cite this article: Bone Joint Res 2024;13(11):632–646

Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Aims. The surgical target for optimal implant positioning in robotic-assisted total knee arthroplasty remains the subject of ongoing discussion. One of the proposed targets is to recreate the knee’s functional behaviour as per its pre-diseased state. The aim of this study was to optimize implant positioning, starting from mechanical alignment (MA), toward restoring the pre-diseased status, including ligament strain and kinematic patterns, in a patient population. Methods. We used an active appearance model-based approach to segment the preoperative CT of 21 osteoarthritic patients, which identified the osteophyte-free surfaces and estimated cartilage from the segmented bones; these geometries were used to construct patient-specific musculoskeletal models of the pre-diseased knee. Subsequently, implantations were simulated using the MA method, and a previously developed optimization technique was employed to find the optimal implant position that minimized the root mean square deviation between pre-diseased and postoperative ligament strains and kinematics. Results. There were evident biomechanical differences between the simulated patient models, but also trends that appeared reproducible at the population level. Optimizing the implant position significantly reduced the maximum observed strain root mean square deviations within the cohort from 36.5% to below 5.3% for all but the anterolateral ligament; and concomitantly reduced the kinematic deviations from 3.8 mm (SD 1.7) and 4.7° (SD 1.9°) with MA to 2.7 mm (SD 1.4) and 3.7° (SD 1.9°) relative to the pre-diseased state. To achieve this, the femoral component consistently required translational adjustments in the anterior, lateral, and proximal directions, while the tibial component required a more posterior slope and varus rotation in most cases. Conclusion. These findings confirm that MA-induced biomechanical alterations relative to the pre-diseased state can be reduced by optimizing the implant position, and may have implications to further advance pre-planning in robotic-assisted surgery in order to restore pre-diseased knee function. Cite this article: Bone Joint J 2024;106-B(11):1231–1239

Aims

This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels.