This study aimed to investigate the optimal sagittal positioning of the uncemented femoral component in total knee arthroplasty to minimize the risk of aseptic loosening and periprosthetic fracture. Ten different sagittal placements of the femoral component, ranging from -5 mm (causing anterior notch) to +4 mm (causing anterior gap), were analyzed using finite element analysis. Both gait and squat loading conditions were simulated, and Von Mises stress and interface micromotion were evaluated to assess fracture and loosening risk.Aims
Methods
This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms. We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.Aims
Methods
The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database.Aims
Methods
The aim of this study was to investigate the safety and efficacy of 3D-printed modular prostheses in patients who underwent joint-sparing limb salvage surgery (JSLSS) for malignant femoral diaphyseal bone tumours. We retrospectively reviewed 17 patients (13 males and four females) with femoral diaphyseal tumours who underwent JSLSS in our hospital.Aims
Methods
At-home softcast removal with no routine clinical follow-up has shown to be safe and effective following paediatric orthopaedic trauma. It minimises clinician contact time and reduces cost. However, there is limited data on the caregiver experience. Retrospective analysis of paediatric fractures requiring application of circumferential softcast that was later removed at home. Two time points were included: (1)July–September 2022, (2)February–April 2023. Demographics data included age, fracture classification, angulation, manipulation requirement, complications or unplanned re-attendance. Caregivers were given an information leaflet on cast removal. Caregivers completed a telephone Likert questionnaire reviewing time taken to remove cast, qualitative descriptors of cast removal and overall satisfaction. 77 families were contacted at mean 93 days post injury. Mean age was 7.5 years. 41(53%) were distal radius and 20(26%) both-bone forearm fractures. The remaining were hand, elbow or tibia injuries. 40(52%) injuries required manipulation under procedural sedation with mean sagittal angulation 24 degrees. 13(17%) patients re-attended with cast problems. Caregivers estimated a mean 13 minutes to remove cast. 83% found it ‘extremely’ or ‘somewhat’ easy. 75% were ‘extremely’ or ‘somewhat’ satisfied. 71% were ‘extremely’ or ‘somewhat’ likely to recommend at-home cast removal. Qualitative descriptors ranged from from ‘traumatising’ to ‘fun’ and ‘straightforward’. The experience at our tertiary centre confirms at-home softcast removal with no further orthopaedic follow-up is safe and feasible, even in those requiring manipulation under sedation. The majority of families reported a positive experience; this however is not universal. Adequate patient information resources are integral to a positive caregiver's experiences.
In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.
Cell culture on tissue culture plastic (TCP) is widely used across biomedical research to understand the
Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA. First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers.Aims
Methods
Mental disorders in particular depression and anxiety have been reported to be prevalent among patients with spinal pathologies. Goal of the current study was to analyze the relationship of Zung pre- and post-op score to other PROs and length of stay. Secondary outcomes included revision surgery and post-operative infections. Data from the international multicenter prospective spine degenerative surgery data repository, DegenPRO v1.1 (AO Spine Knowledge Forum Degenerative) were utilized. Patients undergoing cervical or lumbar procedure were included. Patient's demographics, Charlson Comorbidity Index, surgical information, Zung score, NDI, pain related PROs and EQ-5D, and complications at surgery and at various post-op time periods. Except for hospital duration, data were analyzed, using multivariable mixed linear models. A robust linear regression model was used to assess the association between Zung score and hospital duration. All models were adjusted for gender and age. 42 patients had Zung score administered. Among those patients 22 (52%) were within normal range, 18 (43%) were mildly and 2 (5%) severely depressed. 62% of the patients had a lumbar pathology with fusion procedures being the most common. Median EQ-5D (3L) score at surgery was significantly higher (0.7, IQR: 0.4-0.7) for patients within normal range than for those with mild (0.4, IGR: 0.3-0.7) or severe depression (0.3, IQR: 0.3-0.3, p-value: 0.05). Compared to patients within normal Zung range, mixed models, indicated lower EQ-5D (3L) score values and higher values for neck and arm pain at surgery with both PROs and EQ-5D (3L) improving in patients with depression over the follow-up time. No association was found between Zung score and hospital length of stay. The initial analysis showed that 43% of the patients were mildly depressed and mainly male patients. Zung score was correlated with post-operative improvements in EQ-5D and arm and neck pain PROs.
The aim of this study was to compare the functional and radiological outcomes and the complication rate after nail and plate fixation of unstable fractures of the ankle in elderly patients. In this multicentre study, 120 patients aged ≥ 60 years with an acute unstable AO/OTA type 44-B fracture of the ankle were randomized to fixation with either a nail or a plate and followed for 24 months after surgery. The primary outcome measure was the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score. Secondary outcome measures were the Manchester-Oxford Foot Questionnaire, the Olerud and Molander Ankle score, the EuroQol five-dimension questionnaire, a visual analogue score for pain, complications, the quality of reduction of the fracture, nonunion, and the development of osteoarthritis.Aims
Methods
Knee alignment affects both the development and surgical treatment of knee osteoarthritis. Automating femorotibial angle (FTA) and hip-knee-ankle angle (HKA) measurement from radiographs could improve reliability and save time. Further, if the gold-standard HKA from full-limb radiographs could be accurately predicted from knee-only radiographs then the need for more expensive equipment and radiation exposure could be reduced. The aim of this research is to assess if deep learning methods can predict FTA and HKA angle from posteroanterior (PA) knee radiographs. Convolutional neural networks with densely connected final layers were trained to analyse PA knee radiographs from the Osteoarthritis Initiative (OAI) database with corresponding angle measurements. The FTA dataset with 6149 radiographs and HKA dataset with 2351 radiographs were split into training, validation and test datasets in a 70:15:15 ratio. Separate models were learnt for the prediction of FTA and HKA, which were trained using mean squared error as a loss function. Heat maps were used to identify the anatomical features within each image that most contributed to the predicted angles.Abstract
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As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients. In this prospective study, 177 specimens were collected from 59 revision arthroplasties, including periprosthetic tissues, synovial fluid, and prosthetic sonicate fluid. Each specimen was divided into two, one for mNGS and one for culture. The criteria of the Musculoskeletal Infection Society were used to define PJI (40 cases) and aseptic failure (19 cases).Aims
Methods
Meniscus allograft and synthetic meniscus scaffold (Actifit®) transplantation have shown promising outcomes for symptoms relief in patients with meniscus deficient knees. Untreated chondral defects can place excessive load onto meniscus transplants and cause early graft failure. We hypothesised that combined ACI and allograft or synthetic meniscus replacement might provide a solution for meniscus deficient individuals with co-existing lesions in cartilage and meniscus. We retrospectively collected data from 17 patients (16M, 1F, aged 40±9.26) who had ACI and meniscus allograft transplant (MAT), 8 patients (7M, 1F, aged 42±11) who underwent ACI and Actifit® meniscus scaffold replacement. Other baseline data included BMI, pre-operative procedures and cellular transplant data. Patients were assessed by pre-operative, one-year and last follow-up Lysholm score, one-year repair site biopsy, MRI evaluations.Abstract
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The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential. We searched PubMed, Embase, and the Cochrane Library, with keywords including “knee osteoarthritis” and “mesenchymal stem cells”, up to June 2019. We selected randomized controlled trials (RCTs) that explored the use of MSCs to treat knee OA. The visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), adverse events, and the whole-organ MRI score (WORMS) were used as the primary evaluation tools in the studies. Our meta-analysis included a subgroup analysis of cell dose and cell source.Aims
Methods
This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI. Patients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker.Aims
Methods
The aims of this study were to validate the outcome of total elbow arthroplasty (TEA) in patients with rheumatoid arthritis (RA), and to identify factors that affect the outcome. We searched PubMed, MEDLINE, Cochrane Reviews, and Embase from between January 2003 and March 2019. The primary aim was to determine the implant failure rate, the mode of failure, and risk factors predisposing to failure. A secondary aim was to identify the overall complication rate, associated risk factors, and clinical performance. A meta-regression analysis was completed to identify the association between each parameter with the outcome.Aims
Methods
A novel injectable hydrogel based on DNA and silicate nanodisks was fabricated and optimized to obtain a suitable drug delivery platform for biomedical applications. Precisely, the hydrogel was designed by combining two different type of networks: a first network (type A) made of interconnections between neighboring DNA strands and a second one (type B) consisting of electrostatic interactions between the silicate nanodisks and the DNA backbone. The silicate nanodisks were introduced to increase the viscosity of the DNA physical hydrogel and improve their shear-thinning properties. Additionally, the silicate nanodisks were selected to modulate the release capability of the designed network. DNA 4% solutions were heated at 90°C for 45 seconds and cooled down at 37°C degree for two hours. In the second step, the silicate nanodisks suspension in water at different concentrations (0.1 up to 0.5%) were then mixed with the pre-gel DNA hydrogels to obtain the nanocomposite hydrogels. Rheological studies were carried out to investigate the shear thinning properties of the hydrogels. Additionally, the hydrogels were characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron microscopy. The hydrogels were loaded with the osteoinductive drug dexamethasone and its release was tested in vitro in phosphate buffer pH 7.4. The drug activity upon release was tested evaluating the osteogenic differentiation of human adipose derived stem cells (hASCs) in vitro through analysis of main osteogenic markers and quantification of alkaline phosphatase activity and calcium deposition. Finally, the hydrogels were tested in vivo and injected into cranial defects in rats to assess their biocompatibility and bone regeneration potential. The inclusion of the silicate nanodisks increased the viscosity of the hydrogels and the best results were obtained with the highest concentration of the nanoclay (0.5%). The hydrogels possessed shear-thinning properties as demonstrated by cyclic strain sweep tests and were able to recover their original storage modulus G' upon removal of strain. Such improvement in the injectable properties of the formulated hydrogels was mainly attributed to the formation of electrostatic interactions between the silicate nanodisks and the phosphate groups of the DNA backbone as confirmed by XPS analysis of the O, N, and P spectra. Additionally, laponite was able to sustain the release of the osteoinductive drug dexamethasone which was instead completely released from the DNA-based hydrogels after a week. The drug after being released was still active and promoted the osteogenic differentiation of hASCs as confirmed by ALP expression and expression of main osteogenic markers including ALP and COLA1. Finally, the gels proved to be biocompatible in vivo when injected into cranial defects and promoted bone formation at the periphery of the defect after a month post-treatment. A novel injectable shear-thinning DNA-based hydrogel was characterized and tested for its drug delivery properties. The hydrogel can promote the sustain release of a small molecule like dexamethasone and be biocompatible in vitro and in vivo. Due to these promising findings, the designed system could find also applicability for the delivery of growth factors or other therapeutic molecules.
Previous study reported that intra-articular injection of MgSO4 could alleviate pain related behaviors in a collagenase induced OA model in rats. It provided us a good description on the potential of Mg2+ in OA treatment. However, the specific efficiency of Mg2+ on OA needs to be further explored and confirmed. The underlying mechanisms should be elucidated as well. Increasing attention has been paid on existence of synovial fluid MSCs (SF-MSCs) (not culture expanded) which may participate in endogenous reparative capabilities of the joint. On the other hand, previous studies demonstrated that Mg2+ not only promoted the expression of integrins but also enhanced the strength of fibronectin-integrin bonds that indicated the promotive effect of Mg2+ on cell adhesion, moreover, Mg2+ was proved could enhance chondrogenic differentiation of synovial membrane derived MSCs by modulating integrins. Based on these evidence, we hypothesize herein intra-articular injection of Mg2+ can attenuate cartilage degeneration in OA rat through modulating the biological behavior of SF-MSCs. Human and rat SF-MSCs were collected after obtaining Experimental Ethics approval. The biological behaviors of both human and rat SF-MSCs including multiple differentiation, adhesion, colony forming, proliferation, etc. were determined in vitro in presence or absence of Mg2+ (10 mmol/L). Male SD rats (body weight: 450–500 g) were used to establish anterior cruciate ligament transection and partial medial meniscectomy (ACLT+PMM) OA models. The rats received ACLT+PMM were randomly divided into saline (control) group and MgCl2 (0.5 mol/L) group (n=6 per group). Intra-articular injection was performed on week 4 post-operation, twice per week for two weeks. Knee samples were harvested on week 2, 4, 8, 12 and 16 after injection for histological analysis for assessing the progression of OA. On week 2 and 4 after injection, the rat SF-MSCs were also isolated before the rats were sacrificed for assessing the abilities of chondrogenic differentiation, colony forming and adhesion in vitro. Statistical analysis was done using Graphpad Prism 6.01. Unpaired t test was used to compare the difference between groups. Significant difference was determined at P < 0 .05. The adhesion and chondrogenic differentiation ability of both human and rat SF-MSCs were significantly enhanced by Mg2+ (10 mmol/L) supplementation in vitro. However, no significant effects of Mg2+ (10 mmol/L) on the osteogenic and adipogenic differentiation as well as the colony forming and proliferation. In the animal study, histological analysis by Saffranin O and Toluidine Blue indicated the cartilage degeneration was significantly alleviated by intra-articular injection of Mg2+, in addition, the expression of Col2 in cartilage was also increased in MgCl2 group with respect to control group indicated by immunohistochemistry. Moreover, the OARSI scoring was decreased in MgCl2 group as well. Histological analysis and RT-qPCR indicated that the chondrogenic differentiation of SF-MSCs isolated from Mg2+ treated rats were significantly enhanced compare to control group. In the current study, we have provided direct evidence supporting that Mg2+ attenuated the progression of OA. Except for the effect of Mg2+ on preventing cartilage degeneration had been demonstrated in this study, for the first time, we demonstrated the promoting effect of Mg2+ on adhesion and chondrogenic differentiation of endogenous SF-MSCs within knee joint that may favorite cartilage repair. We have confirmed that the anti-osteoarthritic effect of Mg2+ involves the multiple actions which refer to prevent cartilage degeneration plus enhance the adhesion and chondrogenic differentiation of SF-MSCs in knee joint to attenuate the progression of OA. These multiple actions of Mg2+ may be more advantage than traditional products. Besides, this simple, widely available and inexpensive administration of Mg2+ has the potential on reducing the massive heath economic burden of OA. However, the current data just provided a very basic concept, the exact functions and underlying mechanisms of Mg2+ on attenuating OA progression still need to be further explored both in vitro and in vivo. Formula of Mg2+ containing solution also need to be optimized, for example, a sustained and controlled release delivery system need to be developed for improving the long-term efficacy.
Patellar fractures account for approximately 1% of all fractures. Open reduction and internal fixation is recommended to restore extensor continuity and articular congruity. However, complications such as nonunion and symptomatic hardware, still exist. Furthermore, there is a risk of re-fracturing of the healed bone during the removal of the implants. Magnesium (Mg), a biodegradable metal, has elastic moduli and compressive yield strength that are comparable to those of natural bone. Our previous study showed that released Mg ions enhanced fracture healing. However, Mg-based implants degrade rapidly after implantation and lead to insufficient mechanical strength to support the fracture. Microarc oxidation (MAO) is a metal surface coating that reduces corrosion. We hypothesized that Mg pins, with or without MAO, would enhance fracture healing radiologically, mechanically, and histologically, while MAO would decrease degradation of Mg pins. Patellar fracture was performed on forty-eight 18-week-old female New Zealand White rabbits according to established protocol. Briefly, the patella is osteotomized transversely and a tunnel (1.1mm) was drilled longitudinally through the two bone fragments. A pin (1 mm, stainless steel, Mg, or MAO-Mg) was inserted into the tunnel. The reduced construct was stabilized with a figure-of-eight band wire (⊘ 0.6 mm stainless steel wire). Cast immobilization was applied for 6 weeks. The rabbits were euthanized at week 8 and 12 post-operation. Microarchitecture and mechanical properties of the repaired patella were analyzed with microCT and tensile testing respectively. Histological sections of the repaired patella were stained. To evaluate the effect of the MAO treatment on degradation rate of Mg pin, the volume of the Mg pins in the patella was measured with microCT. At week 8, both Mg and Mg-MAO showed higher ratio of bone volume to tissue volume (BV/TV) than the control while there was no significant different between Mg and Mg-MAO. At week 12, Control, Mg, and Mg-MAO groups showed enlarged patella when compared to the normal patella. Tissue volume (TV) and bone volume (BV) of the patella in Mg and Mg-MAO were larger than those in the Control group. However, the Control had higher ratio of bone volume to tissue volume (BV/TV), TV density, and BV density than Mg and Mg-MAO. Tensile testing showed that the mechanical properties of the repaired patella (failure load, stiffness, ultimate strength, and energy-to-failure) of Mg and Mg-MAO were higher than that of the control at both week 8 and week 12. Histological analysis showed that there was significant new bone formation in the Mg and Mg-MAO group compared with the Control group at week 8 and 12. The degradation rate of the MAO-coated Mg pins was significantly slower than those without MAO at week 8 but no significant difference was detected at week 12. Mechanical, microarchitectural, and histological assessments showed that Mg pins, with or without MAO, enhanced fracture healing of the repaired patella compared to the Control. MAO treatment enhanced the corrosion resistance of the Mg pins at the early time point.
A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing. Cite this article:
