Bone & Joint Research最新文献

Aims: Extendable prostheses have developed rapidly over the decades to solve limb length discrepancy (LLD) following limb salvage surgery in children and adolescents who have suffered primary malignant bone tumours. In this study, we performed a systematic review of the literature on extendable prostheses to investigate their developments and clinical outcomes, to provide evidence-based recommendations for enhancing clinical implementation and refinement.

Methods: A systematic review of 46 studies with 709 invasive cases and 556 noninvasive cases was performed after searching the PubMed, EMBASE, and Web of Science databases. Results of the prosthesis survival rate, functional outcomes, and complications were extracted, recategorized, and analyzed.

Results: With the increase in publication year, there was no significant change in the five-year prosthesis survival rate, while the Musculoskeletal Tumour Society (MSTS) score exhibited an upward trend. Apart from infection, the incidence of mechanical complications increased as follow-up time extended. Failed structure of invasive prosthesis was higher than in those who received a noninvasive extendable prosthesis (25.1% (123/491) vs 15.0% (70/466); p < 0.001, Power = 0.972). The mean number of additional procedures in patients who received an invasive prosthesis was higher than those who received a noninvasive extendable prosthesis (2.4 (1.3 to 3.4) vs 1.4 (0.1 to 2.7); p = 0.021), and there was no obvious clinical difference between invasive prostheses and noninvasive prostheses in infection (15.0% (88/586) vs 13.4% (68/508); p = 0.442, Power = 0.125). Infection (44/361, 12.2%) was the most common complication associated with the Stanmore JTS prosthesis, while the incidence of aseptic loosening (14/296, 4.7%) was the lowest. The mean incidence of complications in the Stanmore Mark I-IV group was higher than that in the Stanmore JTS group (68.9% (104/151) vs 36.6% (49/134); p < 0.001, Power = 0.9998).

Conclusion: Despite decades of progress, extendable prostheses have shown promising results but still face challenges such as high infection rates, requiring further technological innovation for better outcomes.

Aims: Open fractures pose a substantial treatment challenge, with adjacent muscle loss being a major complication. The induced membrane (IM) technique has shown promise in treating complicated fractures. The aim of this study is to investigate the impact of adjacent muscle trauma on segmental fracture healing using recombinant human bone morphogenetic protein-2 (rhBMP-2) via the IM technique.

Methods: Skeletally mature male rats (n = 10 to 11 per group) underwent unilateral 3 mm segmental bone defects (SBD) of the tibial diaphysis or a composite tissue injury (CTI), which included a SBD along with volumetric muscle loss (VML). A polymethyl methacrylate (PMMA) spacer was formed within the SBD of each rat. After a four-week period, the PMMA spacer was removed, and the defect was treated with a rhBMP2-impregnated collagen sponge. Longitudinal micro-CT (µCT) imaging was conducted at baseline (Day 0) and at weeks 2, 4, 8, and 12 post-spacer removal to monitor fracture healing progress. At the 12-week postoperative mark, a comprehensive analysis was conducted, including endpoint µCT analysis, evaluation of neuromuscular function, tibia torsional testing, and histological examination.

Results: Longitudinal µCT scans revealed no differences in bone formation or bone mineral density (BMD) at any timepoint between the SBD and CTI groups. High-resolution µCT analysis at the endpoint also showed no variations in bone quality. Torsion testing confirmed that VML did not affect bone strength. Notably, CTI animals exhibited an irreversible reduction in muscle mass and neuromuscular function, which was not observed in the SBD group.

Conclusion: Introducing the additional challenge of VML alongside SBD did not hinder the effectiveness of the induced membrane technique in healing a critical-sized defect.

Aims: Successful identification of bacteria in tissue samples requires careful consideration of multiple factors, including sample type and quality, the type of bacteria being detected, and the sensitivity and specificity of the detection method. Here, we address the issues of detecting a small number of bacteria, often found in biofilms and heterogeneously distributed in a large volume (the surgical site with suspected infection). Specifically, the study seeks to address the difficulties in detecting small numbers of bacteria, and to evaluate the impact of bacterial aggregation on the probability of successful detection.

Methods: We present simple formulae for the probability of detecting bacteria in different infection scenarios where the number of bacteria and size of bacterial aggregates are incorporated as variables. We define a critical aggregation parameter, above which the probability of sampling bacteria decreases dramatically.

Results: Our calculations demonstrate that aggregation of bacteria in tissues can strongly impact the probability of detection, where an increase in aggregate size results in a reduced probability of obtaining a positive biopsy. Our calculations underscore the challenges in effectively sampling tissue for diagnostic purposes, particularly in low-grade infections characterized by small bacterial quantities within aggregates. Below the critical aggregation parameter, obtaining five tissue specimens is associated with a high probability of detecting infection, but at a higher aggregation level, increasing the number of specimens is rendered ineffective, resulting in culture-negative diagnoses.

Conclusion: We hypothesize that the high false-negative rate in diagnosing orthopaedic surgical site infections, such as periprosthetic joint infections, could be partly influenced by the heterogeneous bacterial distribution and the sampling complexities of such populations outlined here. Homogenization of tissue specimens is a technique to enhance the surface area which potentially could increase the detection of heterogeneously distributed bacteria.

Aims: Increasing the interference fit of the acetabular component can increase primary stability, but it introduces excessive periacetabular strain during impaction, which can lead to fractures. An optimal outcome following cementless acetabular component impaction is maximal primary implant stability with minimal periacetabular bone strain. The aim of this study was to investigate whether a simple modification to a surgeon's reaming technique can achieve this desirable outcome.

Methods: A custom drop rig simulated impaction strikes, seating acetabular components of either 1 mm or 2 mm interference fit into synthetic sawbones with cavities reamed to either a true hemisphere or a hemisphere with an enhanced reaming depth of 2 mm or 4 mm. Synthetic bone strain was recorded using strain gauges, and push-out tests were conducted to assess implant stability. Polar gaps were measured using optimal trackers.

Results: Compared to a true hemispherical cavity, enhancing the reaming depth significantly increased the primary stability of the implant (p < 0.001) while reducing both the periacetabular strain and strain deterioration for both 1 mm and 2 mm interference fit components. A 4 mm reaming depth enhanced the primary stability of 1 mm press-fit components to a level almost equivalent to a 2 mm press-fit, albeit reducing strain to the bone. Enhancing reaming depth did not significantly affect polar gap.

Conclusion: Enhancing cavity reaming depth is a simple technique to increase the implant primary stability of press-fit uncemented acetabular components, while avoiding any excess in periacetabular strain and the associated fracture risk.

Aims: The repair process of ligament ruptures is a complex phenomenon involving three stages: early, repair, and remodelling. This study aimed to investigate the cellular and genetic aspects related to the repair and healing of ligament ruptures using single-cell RNA sequencing (scRNA-seq) on anterior cruciate ligament (ACL) tissues.

Methods: A comprehensive examination was conducted on ACL tissues from three healthy individuals and three patients with ligament ruptures at different timepoints (one week, three weeks, and six months post-injury). A deep gene expression analysis was performed on 83,195 cells obtained from the six cases, and immunohistochemistry techniques were used to identify cell types.

Results: In this study, tenocytes and fibroblasts in ligament tissues were distinctly identified for the first time. Moreover, a total of ten cell populations were discovered in ACL tissues, comprising tenocytes, fibroblasts, macrophages, stromal cells, T cells, endothelial cells, B cells, epithelial cells, chondrocytes, and monocytes. Further analysis of the tenocyte populations revealed ten distinct subtypes, highlighting the diversity of tenocytes in human ACL tissues.

Conclusion: The identification of multiple specialized tenocyte populations in human ACL tissues sheds light on potential avenues for advancing research in cell therapy for ligament injuries. These findings provide valuable insights into the cellular components involved in the repair and healing processes of ligament ruptures, paving the way for future investigations in this field.

Aims: To characterize the effects of varying experimental parameters of transforming growth factor-beta 1 (TGF-β1) in primary knee fibroblasts as an in vitro model of arthrofibrosis.

Methods: Primary knee fibroblasts were isolated from one patient undergoing primary total knee arthroplasty (TKA) and one patient undergoing revision TKA for arthrofibrosis, respectively. Fibroblasts were stimulated with varying concentrations and durations of the pro-fibrotic cytokine TGF-β1. Picrosirius red staining (PSR) was conducted to assess collagen deposition, and real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were performed to determine cellular gene expression levels. A collagen gel contraction assay was used to assess TGF-β1-induced fibroblast contraction.

Results: In our experiments, TGF-β1-mediated collagen deposition was consistent across a vast concentration range (0.5 to 40 ng/ml). While α-smooth muscle actin (ACTA2) protein levels and SMAD2 phosphorylation were induced by low concentrations (1 ng/ml), robust ACTA2 transcription required higher concentrations (5 ng/ml) of TGF-β1. Evaluation of TGF-β1-mediated cell and cytoskeletal contractility shows that in the measured fibroblasts, this process occurs within three hours following TGF-β1 administration. Of note, TGF-β1-differentiated myofibroblasts exhibited greater contractile properties than naïve fibroblasts in the presence of TGF-β1.

Conclusion: Taken together, this study elucidates key TGF-β1 experimental parameters that will inform the development and interpretation of in vitro models of arthrofibrosis.

Aims: The formation of a postoperative epidural scar induced by epidural fibrosis is the main reason for recurrence of lumbar disc herniation after laminectomy. Hederagenin (HE) has been found to be widely present in various medicinal plants and has various pharmacological functions. This study aimed to investigate the effect and regulatory mechanism of HE on epidural scar formation.

Methods: Transforming growth factor beta 1 (TGF-β1)-stimulated epidural scar fibroblasts were used as an in vitro cell model. Based on that, HE treatment was carried out along with sirtuin-6 (SIRT6) silence or protein arginine N-methyltransferase 1 (PRMT1) overexpression. The interaction between SIRT6 and PRMT1 was evaluated by pulldown and co-immunoprecipitation (CoIP) assays. Then, cell proliferation, apoptosis, and fibrosis were measured by Cell Counting Kit (CCK)-8, flow cytometry, and western blotting. Moreover, the effects of receptor activator of nuclear factor-κB ligand (RANKL) supplementation and endoplasmic reticulum (ER) stress were also evaluated by supplementing recombinant protein and specific inhibitor or activator.

Results: HE depressed cell proliferation and fibrosis, while inducing apoptosis of epidural fibroblasts. Meanwhile, HE promoted SIRT6 expression which suppressed PRMT1 acetylation and protein stability. Additionally, HE induced ER stress and upregulated RANKL in epidural fibroblasts via mediating SIRT6/PRMT1 axis.

Conclusion: Generally, the therapeutic role of HE treatment on epidural scar formation was exerted by regulating SIRT6/PRMT1 axis-mediated ER stress and RANKL pathway. This study provides evidence of a novel therapeutic measure for epidural scar formation.

Aims: The Latarjet procedure is the treatment of choice for patients who have recurrent anterior shoulder instability with glenoid bone loss. However, the stabilizing effect of the Latarjet procedure in patients is sparsely described. The aim of this study was to evaluate the glenohumeral joint (GHJ) kinematics during an apprehension-relocation test in patients with anterior shoulder instability before and after their Latarjet procedure, and in comparison with their contralateral healthy shoulder.

Methods: A total of 20 patients scheduled for the Latarjet procedure were enrolled. The patients were examined preoperatively with bilateral radiostereometric analysis (RSA) and one year after surgery on the operated shoulder with an apprehension-relocation test. Bone models were obtained from CT scans and aligned with the RSA images. The GHJ kinematics was evaluated with two methods: the humeral head centre location relative to the glenoid centre, and the GHJ contact point relative to the glenoid centre.

Results: No difference in GHJ kinematics was found between the healthy and the postoperative GHJ. Compared with the preoperative injured shoulder, the postoperative mean (95% CI) humeral head centre was 0.8 mm (0.1 to 1.4) more superior and 0.7 mm (-0.1. to 1.4) more posterior during the apprehension test, and 0.5 mm (0.0 to 1.1) more posterior during the relocation test. The postoperative contact point was posterior to the coracoid bone block and 0.9 mm (-0.2 to 2.0) more posterior than in the preoperative injured shoulder during the apprehension test. The articulating area of the coracoid bone block was decreased by 63.9% (75.5 to 114.6) one year after surgery.

Conclusion: The Latarjet procedure restored the humeral head centre location posterior and superior, and the contact point posterior, to the coracoid bone block. This suggests that the stabilizing effect of the GHJ following the Latarjet procedure is primarily due to the conjoined tendon rather than the coracoid bone block itself.

Aims: To assess whether it was feasible to objectively measure activity behaviour between robotic arm-assisted (raTKA) and manually performed (mTKA) total knee arthroplasty using the ActivPAL accelerometer.

Methods: A randomized controlled trial was undertaken and a subgroup of 40 patients underwent physical activity assessment. Patients were randomized to either mTKA (n = 18) or raTKA (n = 22). Preoperative (baseline) and 12-month postoperative physical activity assessment were undertaken using the ActivPAL accelerometer in addition to patient-reported outcome measures (PROMs): Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Forgotten Joint Score (FJS), EuroQol five-dimension questionnaire (EQ-5D), and EuroQol visual analogue scale (EQ-VAS). At 12 months, 15 patients in the raTKA group and nine in the mTKA group had paired ActivPAL data for analysis. Of the 16 patients without data, four withdrew, four were not provided with the ActivPAL due to logistical reasons, one failed to return the ActivPAL, one was allergic to the ActivPAL patch, and six failed to record or the data were corrupt.

Results: There were no significant differences in the improvement in standing time (mean difference (MD) 1.6, p = 0.924), step number (MD 62.0, p = 0.970), sitting time (16.3, p = 0.777), number of sit-to-stand transitions (MD 16.3, p = 0.579), or activity scores (MD 0.0, p = 0.977) between the groups. However, the raTKA had a clinically meaningful and significantly (MD 19.8, 95% CI 0.8 to 38.8; p = 0.041) greater improvement in knee-specific pain according to the WOMAC pain score. There were no other statistically significant (p ≥ 0.113) differences between the other PROMs. There were no significant (p ≥ 0.144) correlations between changes in measures of physical activity functional assessments.

Conclusion: Objectively assessed physical activity was logistically difficult due to patient and data loss. There were no differences in activity with small effect sizes (≤ 0.2) between the raTKA and mTKA groups, despite differences in subjective knee pain. Improvement in subjective PROMs did not correlate with objectively measured physical activity, and the two seemed to be independent of one another.

Aims: Fracture-related infections and the associated treatment failure burden our society and healthcare system significantly. As an alternative approach, we investigated the effect of non-contact induction heating (NCIH) against Staphylococcus aureus within mature biofilms. In addition, we assessed the ability of antibiotics, the antimicrobial peptide SAAP-148, and bacteriophage (phage) ISP to enhance the efficacy of NCIH, thereby allowing the use of lower temperatures during NCIH.

Methods: Clinical isolates of methicillin-resistant and methicillin-sensitive S. aureus (methicillin-resistant S. aureus (MRSA), methicillin-sensitive S. aureus (MSSA)) were cultured for seven days on Ti-6Al-7Nb (mimicking fracture plates) discs to obtain mature biofilms. Biofilms were exposed to 60°C to 80°C NCIH. In addition, biofilms were sequentially exposed to 60°C to 70°C NCIH and rifampicin/ciprofloxacin, SAAP-148, or phage ISP. Biofilm-embedded bacteria were harvested by sonication to determine the bacterial load and visualized by confocal microscopy (LIVE/DEAD).

Results: NCIH to 60°C, 70°C, and 80°C reduced biofilm-embedded MRSA and MSSA by 2.3-log, 4.9-log, 5.5-log, and 1.1-log, 3.4-log, and 6.6-log CFU/ml, respectively. LIVE/DEAD staining revealed NCIH-induced bacterial cell death throughout the biofilm layers. The sequential combination of rifampicin/ciprofloxacin at 10 µg/ml and 1,280 µg/ml (MRSA) or 156 µg/l and 64 µg/ml (MSSA) and 70°C NCIH synergistically reduced biofilm-embedded bacteria by 2.7-log and 3.7-log CFU/ml, respectively, while the alternating exposure order reduced bacterial counts by -0.1 and 1.7-log CFU/ml. SAAP-148 at 51.2 µM followed by 70°C NCIH further diminished biofilm-embedded MRSA and MSSA by 2.3-log and 1.5-log CFU/ml, respectively. No significant reductions were observed for NCIH combined with phage ISP compared to these treatments alone.

Conclusion: NCIH effectively reduced biofilm-embedded S. aureus on Ti-6Al-7Nb in a heat-dependent fashion. Rifampicin/ciprofloxacin and SAAP-148, but not phage ISP, enhanced the efficacy of NCIH. Antibiotic exposure at suboptimal concentrations followed by NCIH was more effective than vice versa, suggesting that the application of this approach might be most suitable in clinical situations where antibiotic treatment has already started.