bluuebunny/crossref_metadata_2025_split huggingface dataset:
MICROSTRUCTURAL AND TRANSCRIPTOMIC ANALYSIS OF TRABECULAR BONE IN PATIENTS WITH IDIOPATHIC OSTEONECROSIS OF THE FEMORAL HEAD
Authors: Quero L. S. , Duch C. E. , Vilaboa Díaz N. , Rey E. G. 
Published: November 2024

IntroductionThe most frequent diagnosis in young adults undergoing total hip arthroplasty (THA) is osteonecrosis of the femoral head (ONFH), an evolving and disabling condition with an increasing prevalence worldwide. Treatment of ONFH remains a challenge mainly because of a lack of understanding of the disease's pathophysiological basis. This study investigated the biological processes that could be affected by ONFH by comparing the microstructure, histological characteristics and transcriptomic profile of trabecular bone from the femoral head (FH) and the intertrochanteric region (IT) of patients suffering from this condition.MethodA total of 18 patients with idiopathic ONFH undergoing THA in our institution were included. Trabecular bone explants were taken intraoperatively from the FH and the IT of patients. Bone microstructure was examined by micro-computed tomography (micro-CT). After bone sectioning, histological features were studied by hematoxylin and eosin staining. Differential gene expression was investigated using a microarray platform.ResultMicro-CT imaging showed higher trabecular separation and lower trabecular thickness and bone volume in trabecular bone from the FH than from the IT. Histological staining revealed that the number of osteoblasts on the bone surface and the percentage of empty lacunae were higher in trabecular bone from the FH. Transcriptome analysis identified a differential signature in trabecular bone from the FH compared to the IT. The gene ontology analyses of the genes overexpressed in trabecular bone from the FH revealed a range of enriched biological processes related to cell division and immune response. In contrast, most downregulated transcripts were involved in bone formation.ConclusionThis study identified changes in the microarchitecture, histological features and transcriptomic signature of trabecular bone from the FH of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. This work was supported by PI22/00939 grant from ISCIII-FEDER-MICINN-AES and Luis Alvarez grant from IdiPAZ.
RETURN TO SPORT AMONG 1,926 PATIENTS WITH HIP DYSPLASIA AFTER UNDERGOING PERIACETABULAR OSTEOTOMY
Authors: Tønning L. , Jakobsen S. S. , Kemp J. , O’Brien M. , Dalgas U. , Mechlenburg I. 
Published: November 2024

IntroductionSymptomatic hip dysplasia is often treated with periacetabular osteotomy (PAO). Studies investigating the effect of PAO have primarily focused on radiographic measurements, pain-related outcomes, and hip survival whereas evidence related to sport participation is limited.MethodsAll patients in our institutional database were deemed eligible for this cohort study if they underwent PAO and had answered at least one question related to sport participation. Patients were asked if they were playing sport preoperatively, 6 months after PAO as well as 2, 5, 10, 15 and 20 years after. In addition, patients were asked if they were able to play their preferred sport, what type and at what level they were playing sport, and if surgery had improved their sport performance.ResultsAmong 2398 patients surveyed, 1926 (80%) were included and 56% were playing sport 6 months after PAO. This number was 61% two years after PAO, and remained around that for the following years, before dropping 15 years after PAO. Between 56% and 71% of patients felt that their sporting performance improved following PAO at the different time points. Between 39% (6 months after PAO) and 63% (15 years after PAO) were able to participate in their preferred sport.ConclusionThe majority of patients undergoing PAO due to hip dysplasia will return to, and maintain, sport after PAO. More than half of patients undergoing PAO believe that the surgery improved their sports performance, and long after the surgery more than half of patients undergoing PAO are able to play their preferred sport.
ADOLESCENT PORCINE STIFLE JOINT AS A MODEL FOR ACL BIOMECHANICS: EFFECTS OF AXIAL AND TORSIONAL LOADS
Authors: Koh J. , Mungalpara N. , Chang N. , Devi I. M. P. , Hutchinson M. , Amirouche F. 
Published: November 2024

IntroductionUnderstanding knee joint biomechanics is crucial, but studying Anterior cruciate ligament (ACL) biomechanics in human adolescents is challenging due to limited availability cadaveric specimens. This study aims to validate the adolescent porcine stifle joint as a model for ACL studies by examining the ACL's behavior under axial and torsion loads and assessing its deformation rate, stiffness, and load-to-failure.MethodsHuman knee load during high-intensity sports can reach 5-6 times body weight. Based on these benchmarks, the study applied a force equivalent to 5-times body weight of juvenile porcine samples (90 pounds), estimating a force of 520N. Experiments involved 30 fresh porcine stifle joints (Yorkshire breed, Avg 90 lbs, 2-4 months old) stored at -22°C, then thawed and prepared. Joints were divided into three groups: control (load-to-failure test), axially loaded, and 30-degree torsion loaded. Using a servo-hydraulic material testing machine, the tibia's longitudinal axis was aligned with the load sensor, and specimens underwent unidirectional tensile loading at 1 mm/sec until rupture. Data on load and displacement were captured at 100 Hz.ResultsOne-way ANOVA showed statistically significant differences in maximum failure force among loading conditions (p = 0.0039). Post hoc analysis indicated significant differences between the control and 500N (non-twisted) groups (p = 0.014) and between the control and 500N (twisted) groups (p = 0.003). However, no significant difference was found between 500N (non-twisted) and 500N (twisted) groups (p = 0.2645). Two samples broke from the distal femur growth plates, indicating potential growth plate vulnerability in adolescent porcines.ConclusionsThe study validates the adolescent porcine stifle joint as a suitable model for ACL biomechanical research, demonstrating that torsional loads are as damaging to the ACL's integrity as equivalent axial loads. It also highlights the potential vulnerability of growth plates in younger populations, reflected in the porcine model.
IMPROVED HUMAN TENOCYTE VIABILITY BY APPLYING PHYSIOLOGICALLY RELEVANT MECHANICAL LOADS IN A PERFUSION BIOREACTOR SYSTEM
Authors: Machain T. C. , Kharchenko A. , Hostettler R. , Lippl J. , Mouthuy P. A. 
Published: November 2024

IntroductionSupraspinatus tears comprise most rotator cuff injuries, the leading cause of shoulder pain and an increasing problem with ageing populations. Surgical repair of considerable or persistent damages is customary, although not invariably successful. Tissue engineering presents a promising alternative to generate functional tissue constructs with improved healing capacities. This study explores tendon tissue constructs’ culture in a platform providing physiological mechanical stimulation and reports on the effect of different loading regimes on the viability of human tendon cells.MethodPorcine decellularized tendon scaffolds were fixed into flexible, self-contained bioreactor chambers, seeded with human tenocytes, allocated in triplicates to either static control, low (15±0.8Newtons [N]), medium (26±0.5N), or high (49±2.1N)-force-regime groups, connected to a perfusion system and cultured under standard conditions. A humanoid robotic arm provided 30-minute adduction/abduction stimulation to chambers daily over a week. A metabolic activity assay served to assess cell viability at four time points. Statistical significance = p<0.05.ResultOne day after beginning mechanical stimulation, chambers in the medium and high-force regimes displayed a rise in metabolic activity by 3% and 5%, respectively. By the last experimental day, all mechanical stimulation regimes had induced an augment in cell viability (15%, 57% and 39% with low, medium, and high loads, respectively) matched against the static controls. Compared to all other conditions, the medium-force regime prompted an increased relative change in metabolic activity for every time point set against day one (p<0.05).ConclusionHuman tenocytes’ viability reflected by metabolic activity in a physiologically relevant bioreactor system is enhanced by loading forces around 25N when mechanically stimulating using adduction/abduction motions. Knowing the most favourable load regime to stimulate tenocyte growth has informed the ongoing exploration of the distinctive effect of different motions on tendon regeneration towards engineering tissue grafts. This work was supported by the Engineering and Physical Sciences Research Council EP/S003509/1.
CHARACTERIZING THE SURFACE DEGRADATION OF OSTEOARTHRITIC CARTILAGE BASED ON RAMAN SPECTROSCOPY AND INVESTIGATING ITS MECHANO-TRIBOLOGICAL PROPERTIES
Authors: Mahadeshwara M. R. , Pandit H. , Hall R. M. , Jawad M. A. , Bryant M. , Gendy R. E. 
Published: November 2024

IntroductionOsteoarthritis (OA) occurs due to a multi-scale degradation of articular cartilage (AC) surface which aggravates the disease condition. Investigating the micro-scale structural alterations and mechano-tribological properties facilitates comprehension of disease-mechanisms to improve future injectable-therapies. This study aims to analyze these properties using various experimental and analytical methods to establish correlations between their morpho-physiological features.MethodIn this study, Raman-spectroscopy was used to investigate microscale changes in AC constituents and categorize OA damage regions in knee-joint samples from joint replacement patients (Samples = 5 and Regions = 40). Following, microscale indentation and sliding tests were performed on these regions to evaluate variations in aggregate-modulus (AM) and elastic-modulus (EM), with coefficient of friction (COF). Finally, scanning electron microscopy (SEM) was employed to analyze these morphological variations.ResultRaman spectroscopy revealed degree of collagen-damage (Amide-3 α-helix to random-coil ratio I-1250/I-1280), proteoglycan-damage (Sulphated bonds SO3- to CH2 twist ratio I-1065/I-1206), amount of bone exposure (Phosphated-hydroxyapatite PO43- to Amide-1 ratio I-959/I-1669) and increased crystallinity (Carbonated hydroxyapatite CO32- to Amide-1 ratio I-1075/I-959) in ECM. Subsequently, these regions were categorized into different groups (G) based on these damages; G1 (Proteoglycan); G2 (Collagen + Proteoglycan); G3 (Collagen + Proteoglycan + Carbonated crystallinity) G4 (Collagen or Proteoglycan + bone exposure); and G5 (Collagen + Proteoglycan + Bone exposure). Further experimentation revealed the differences in mechano-tribological properties (AM, EM, and COF) between the different groups. G5 displayed the highest values of AM (1.5 ± 0.2MPa), EM (0.3 ± 0.01MPa) and COF (0.39 ± 0.08), compared to other groups. These altered properties were confirmed via SEM that revealed micro-asperity junctions, superficial fronding, fibrillations and bone exposure at these damaged regions.ConclusionThis study demonstrated micro-scale changes in AC among OA patients commensurate to the degree of tissue damage, which correlates with disease progression altering joint structure and function particularly in regions with high COF.
IN VITRO CO-CULTURE OF TISSUE-ENGINEERED MINERALIZED CARTILAGE AND VESSEL NETWORKS TO MODEL ENDOCHONDRAL OSSIFICATION
Authors: Ji E. , Leijsten L. , Bouma J. W. , Rouchon A. , Maggio N. D. , Banfi A. , Osch G. V. , Farrell E. , lolli A. 
Published: November 2024

IntroductionEndochondral ossification (EO) is the process of bone development via a cartilage template. It involves multiple stages, including chondrogenesis, mineralisation and angiogenesis. Importantly, how cartilage mineralisation affects angiogenesis during EO is not fully understood. Here we aimed to develop a new in vitro co-culture model to recapitulate and study the interaction between mineralised cartilage generated from human mesenchymal stromal cells (hMSCs) and microvascular networks.MethodChondrogenic hMSC pellets were generated by culture with transforming growth factor (TGF)-β3. For mineralised pellets, β-glycerophosphate (BGP) was added from day 7 and TGF-β3 was withdrawn on day 14. Conditioned medium (CM) from the pellets was used to evaluate the effect on human umbilical vein endothelial cells (HUVECs) in migration, proliferation and tube formation assays. To perform direct co-cultures, pellets were embedded in fibrin hydrogels containing vessel-forming cells (HUVECs, adipose stromal cells) for 10 days with BGP to induce mineralisation. The pellets and hydrogels were characterised by immunohistochemistry and confocal imaging.ResultThe CM from d14 chondrogenic or mineralised pellets significantly stimulated HUVEC migration and proliferation, as well as in vitro vascular network formation. When CM from pellets subjected to prolonged mineralisation (d28) was used, these effects were strongly reduced. When chondrogenic and mineralised pellets were directly co-cultured with vessel-forming cells in fibrin hydrogels, the cartilage matrix (collagen type II/X stainings) and the mineral deposition (von Kossa staining) were well preserved. Confocal imaging analyses demonstrated the formation of microvascular networks with well-formed lumina. Importantly, more microvascular structures were formed in the proximity of chondrogenic pellets than mineralized pellets.ConclusionThe angiogenic properties of tissue engineered cartilage are significantly reduced upon prolonged mineralisation. We developed a 3D co-culture model to study the role of angiogenesis in endochondral bone formation, which can have applications in disease modelling studies.
PIEZO1 AS A MEDIATOR OF CHONDROCYTE NUCLEAR MECHANICS AND CHROMATIN METHYLATION STATE
Authors: Castorena J. G. , Riester R. , Ornelas M. G. , Guilak F. , Danalache M. 
Published: November 2024

IntroductionPiezo1 is a mechanosensitive Ca2+ ion channel that has been shown to transduce hyper-physiologic mechanical loads in chondrocytes. In osteoarthritic cartilage, Piezo1 expression was shown to be upregulated by interleukin-1 alpha (IL-1α) and resulted in altered calcium dynamics and actin cytoskeleton rarefication. Together these studies highlight the importance of Piezo1 channels during joint injury. However, the mechanism by which Piezo1 regulates chondrocyte physiology and mechanotransduction during homeostasis is still largely unknown. In this study, we investigate the impact of Piezo1 activation on nuclear mechanics and chromatin methylation state.MethodsPorcine chondrocytes (n=3-5 pigs) were treated with Yoda1, a Piezo1-specific agonist, for either 2, 5, 15 or 180 minutes. To characterize chromatin state, we monitored the abundance of a chromatin methylation marker (H3K9Me3) using immunofluorescence (IF). Atomic force microscopy (AFM, 25 nm cantilever) was employed to quantify the nuclear elastic modulus (NEM) of individual cell nuclei. To explore the interplay between cytoskeletal dynamics and nuclear mechanics, chondrocytes were treated with Latrunculin A (LatA), an actin polymerization inhibitor.ResultIF experiments showed chromatin methylation was the lowest 2 minutes post Yoda1 activation of Piezo1 (p=0.027). Additionally, we found that 2 or 5 minutes post-Piezo1 activation resulted in a significantly lower NEM when compared to the control (p<0.00001). The observed decrease in NEM at 2 and 5 minutes post-Piezo1 activation was not observed after knocking down Piezo1 (p>0.99). In LatA treated cells, the elevated NEM persisted even after Piezo1 activation with Yoda1 (p>0.75).ConclusionThese findings illuminate the mechanism by which Piezo1 activation and actin remodeling regulate transient mechanotransduction during homeostasis. Further research into the transient decrease in nuclear stiffness and chromatin methylation observed during the initial 5 minutes of Piezo1-induced Ca2+ signaling, may contribute to a better understanding of the role of Piezo1 channels in joint injury and development of therapeutic interventions for osteoarthritis.
RISK FACTORS FOR DEVELOPMENTAL DYSPLASIA OF THE HIP AT THREE MONTHS OF AGE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tirta M. , Rahbek O. , Kold S. , Husum H. C. 
Published: November 2024

IntroductionSelective screening of children at risk for developmental dysplasia of the hip (DDH) is based on clinical examination and risk factor identification. Two meta-analyses published in 2012 found breech presentation, family history of DDH, female sex and primiparity to increase the risk of DDH. However, the DDH definition, reference tests and age of the examined children vary considerably, complicating the translation of those findings to current screening guidelines. The aim of this meta-analysis was to evaluate the association of previously proposed risk factors to the risk of sonographically verified DDH.MethodWe searched PubMed, EMBASE and Cochrane library to identify cohort, RCTs, case-control and cross-sectional studies from 1980 to 2023 in English language. Eligible studies included participants under three months of age, where the diagnosis of DDH was made by hip ultrasound using the gold standard Graf method and reported information on one or more of the proposed risk factors and final diagnosis was available.ResultOf 5363 studies screened, 20 studies (n=64543 children) were included. Breech presentation (OR: 4.2, 95%CI 2.6-6.6), family history (3.8, 95%CI 2.1-7.2), female sex (2.5, 95%CI 1.7-3.6), oligohydramnios (3.8, 95%CI 1.7-8.5) and high birthweight (2.0, 95%CI 1.6-2.5) significantly increased the risk of DDH. C-section, primiparity, multiple births, low birthweight and prematurity were not found to increase the risk for DDH, and there was only one study about clubfoot as a risk factor. Heterogeneity was high (I2>75%) in all the tested factors except high birthweight (I2=0%). Subgroup analysis was performed to investigate these heterogeneities.ConclusionFamily history of DDH and breech presentation are associated with significant increase of the risk of sonographic DDH in children aged three months. A similar risk increase was detected for oligohydramnios, which was not detected in previous meta-analyses. Additionally, the DDH risk increase of female sex was found to be lower than previously reported.
RISKS FOR REOPERATION TO PROMOTE UNION IN PERIPROSTHETIC DISTAL FEMUR FRACTURES
Authors: Schlauch A. , Shah I. , Crawford B. , Martin A. , Denisov A , Tamer P. , Farrell B. 
Published: November 2024

IntroductionDistal femur fractures around a total knee arthroplasty (TKA) are a growing problem for orthopaedic surgeons. The purpose of this study was to identify risks of reoperation for nonunion following open reduction and internal fixation of TKA periprosthetic distal femur fractures (PDFF).MethodPatients with PDFF (AO 33A-C[VB1, C1, D1], Su types 1-3) managed operatively with open reduction and internal fixation (ORIF) were retrospectively reviewed. Exclusion criteria were acute management with a distal femur replacement, less than 6 months of follow-up, and lack of injury or follow-up radiographs. The primary outcome measure was reoperation to achieve bony union. Comparisons were made between cases that did and did not require a reoperation to achieve union. Univariate analysis was used to identify factors to be analyzed in multivariate analysis to determine independent risk factors for the primary outcome.ResultA total of 77 patients met inclusion criteria. Union rate was 69/77 (89.6%). There were no differences between the groups for age, sex, BMI, comorbidities, Su classification, open injury, or mechanism of injury. Multivariate analysis identified risks for nonunion including post-operative malalignment (OR 1.41; CI 1.20-1.64; p<0.001), notching pre-operatively (OR 1.22; CI 1.04-1.42; p=0.012), presence of screws through fracture line (OR 1.28; CI 1.17-1.39; p<0.001), plate length <12 holes (OR 1.16; CI 1.02-1.33; p=0.024) and screw density greater than 0.4 (OR 2.18; CI 1.25-3.78; p=0.006)ConclusionThe reoperation rate to promote union was 10.4%. The study identified post-operative malalignment, notching pre-operatively, presence of screws through fracture line, plate length <12 holes, and proximal screw density greater than 40% as independent risk factors for nonunion.
INITIAL CONSTRUCT STABILITY OF LONG CEPHALOMEDULLARY NAILS WITH CONVENTIONAL DISTAL LOCKING COMPARED TO SIMILAR NAILS WITH SUPERIOR LOCKING FOR COMPLEX TROCHANTERIC FRACTURES AO31-A2.2: A BIOMECHANICAL STUDY
Authors: Schulz A. P. , Münch M. , Barth T. , Frese J. , Hinz N. , Hartel M. 
Published: November 2024

IntroductionA long nail is often recommended for treatment of complex trochanteric fractures but requires longer surgical and fluoroscopy times. A possible solution could be a nail with an appropriate length which can be locked in a minimally invasive manner by the main aiming device. We aimed to determine if such a nail model* offers similar structural stability on biomechanical testing on artificial bone as a standard long nail when used to treat complex trochanteric fractures.MethodAn artificial osteoporotic bone model was chosen. As osteosynthesis material two cephalomedullary nails (CMN) were chosen: a superior locking nail (SL-Nail) which can be implanted with a singular targeting device, and a long nail (long-nail) with distal locking using free-hand technique. AO31-A2.2 fractures were simulated in a standardized manner. The insertion of the nail was strictly in accordance with the IFU and surgical manual of the manufacturer. The nail was locked dynamically proximally and statically distally. Axial height of the construct, varus collapse, and rotational deformity directly after nail insertion were simulated. A Universal Testing Machine was used. Measurements were made with a stereo-optic tracking system. Reactive movements were recorded and evaluated in all six degrees of freedom. A comparative analysis provided information about the stability and deformation of the assemblies to be compared.ResultThere was a detectable difference in the axial fracture movement resulting in narrowing of the fracture gap. The load displacement was 1.7mm higher for the SL-Nail. There was no difference in varus collapse or rotational deformity between the nail variants.ConclusionWe conclude that there are small differences which are clinically insignificant and that a superior locking nail can safely be used to manage complex trochanteric fractures.*DCN SL nail, SWEMAC, Linköping, SwedenFunding: no funding
LONG-TERM OUTCOMES FOLLOWING TUMOUR RESECTION AND VASCULARIZED FIBULAR GRAFTING IN DENMARK
Authors: Nielsen C. L. 
Published: November 2024

IntroductionVascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. This study aimed to assess the surgical and oncological outcomes of patients treated in Denmark between 2010 and 2022.MethodWe present a retrospective review of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (range: 2-39), and the median follow-up was 82 months (range: 12-138). Patients were analyzed overall and stratified into upper and lower extremity groups based on tumor location.ResultThe primary rate of graft union was 63%, and after secondary procedures, the overall rate of graft union was 67%, with a median time to union of 13 months (range: 7-29). The reoperation rate was 74%, while the rate of limb salvage was 93%, with two patients undergoing amputation during follow-up. The 5-year overall survival rate was 81% (95% CI: 61-92). Patients with upper extremity tumors were more likely to attain graft union (92% vs. 47%, p=0.02) and less likely to undergo multiple reoperations (17% vs 60%, p=0.047) compared to patients with lower extremity tumors.ConclusionVascularized fibula grafting remains a valuable option in limb salvage surgery with acceptable long-term outcomes. However, especially in lower extremity cases, a low rate of graft union and multiple reoperations are to be expected.