bluuebunny/crossref_metadata_2025_split huggingface dataset:
COMPARISON OF POSTOPERATIVE CLINICAL OUTCOMES BETWEEN CRUCIATE-RETAINING AND RESECTING TOTAL KNEE ARTHROPLASTY WITH A CRUCIATE-SUBSTITUTING INSERT
Authors: Kato K. , Hayashi S. 
Published: November 2024

PurposeTo compare postoperative clinical outcomes between posterior cruciate ligament (PCL) retaining and resecting total knee arthroplasty (TKA) using same cruciate-substituting (CS) inserts, and to elucidate the clinical relevance of the residual PCL in cruciate-retaining TKA, considering intraoperative influence factors, such as the posterior tibial slope, posterior condylar offset, joint gap, joint balance, and joint laxity.MethodsA total of 64 consecutive knees (44 patients) were enrolled in this study and divided into following two groups: 39 knees underwent PCL-retaining TKA group (CR group), and 25 underwent PCL-resecting TKA group (CS group). Preoperative patients’ demographic data and one-year postoperative clinical outcomes including range of motion, the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Japanese Orthopaedic Association (JOA) score, and Forgotten Joint Score-12 (FJS-12) were compared between two groups.ResultsRegarding range of motion, the average preoperative ROM was -14.3/120.0 degrees in the CR group and improved to -2.4/118.9 degrees postoperatively. In the CS group, the average preoperative ROM was -7.5/130 degrees and changed to -2.2/122.4 degrees postoperatively. There was no significant difference in the postoperative ROM between the groups (P=0.16). The KOOS (from 47.1 to 69.5 in CR group; from 41.1 to 70.8 in CS group) and JOA scores (from 59.2 to 76.9 in CR group; from 55.6 to 80.8 in CS group) were significantly improved postoperatively in both groups (P < 0.01). However, there was no significance in these postoperative scores between two groups (P = 0.09). There was also no significance in FJS-12 between two groups (70.3 in CR group and 66.9 in CS group; P=0.53).ConclusionsResidual PCL in TKA with a CS insert would not impact one-year postoperative clinical outcomes including KOOS, JOA, and FJS-12.
TAILOR-MADE NANOSWITCHES FOR TARGETED MODULATION OF PIEZO1 MECHANOSENSING INFLUENCE STEM CELL FATE
Authors: Teixeira S. P. B. , Pardo A. , Taboada P. , Wolleb M. , Snedeker J. , Reis R. L. , Gomes M. M. E. , Domingues R. M. A. 
Published: November 2024

IntroductionPIEZO mechanoreceptors are increasingly recognized to play critical roles in fundamental physiological processes like proprioception, touch, or tendon biomechanics. However, their gating mechanisms and downstream signaling are still not completely understood, mainly due to the lack of effective tools to probe these processes. Here, we developed new tailor-made nanoswitches enabling wireless targeted actuation on PIEZO1 by combining molecular imprinting concepts with magnetic systems.MethodTwo epitopes from functionally relevant domains of PIEZO1 were rationally selected in silico and used as templates for synthesizing molecularly imprinted nanoparticles (MINPs). Highly-responsive superparamagnetic zinc-doped iron oxide nanoparticles were incorporated into MINPs to grant them magnetic responsiveness. Endothelial cells (ECs) and adipose tissue-derived stem cells (ASCs) incubated with each type of MINP were cultured under or without the application of cyclical magnetomechanical stimulation. Downstream effects of PIEZO1 actuation on cell mechanotransduction signaling and stem cell fate were screened by analyzing gene expression profiles.ResultNanoswitches showed sub-nanomolar affinity for their respective epitope, binding PIEZO1-expressing ECs similarly to antibodies. Expression of genes downstream of PIEZO1 activity significantly changed after magnetomechanical stimulation, demonstrating that nanoswitches can transduce this stimulus directly to PIEZO1 mechanoreceptors. Moreover, this wireless actuation system proved effective for modulating the expression of genes related to musculoskeletal differentiation pathways in ASCs, with RNA-sequencing showing pronounced shifts in extracellular matrix organization, signal transduction, or collagen biosynthesis and modification. Importantly, targeting each epitope led to different signaling effects, implying distinct roles for each domain in the sophisticated function of these channels.ConclusionThis innovative wireless actuation technology provides a promising approach for dissecting PIEZO-mediated mechanobiology and suggests potential therapeutic applications targeting PIEZO1 in regenerative medicine for mechanosensitive tissues like tendon.AcknowledgementsEU's Horizon 2020 ERC under grant No. 772817 and Horizon Europe under grant No. 101069302; FCT/MCTES for PD/BD/143039/2018, COVID/BD/153025/2022, 10.54499/2020.03410.CEECIND/CP1600/CT0013, 10.54499/2022.05526.PTDC, 10.54499/UIDB/50026/2020, 10.54499/UIDP/50026/2020, and 10.54499/LA/P/0050/2020.
TRICARBOXYLIC ACID CYCLE INTERMEDIATE A-KETOGLUTARATE PRESERVES BONE FORMATION AND COUNTERACTS OSTEOPOROSIS DEVELOPMENT
Authors: Chen Y. S. , Lian W. S. , Lin Yu-Han , Wang Feng-Sheng 
Published: November 2024

IntroductionPromoting bone mass homeostasis keeps skeleton away from osteoporosis. a-Ketoglutarate (a-KG) is an indispensable intermediate of tricarboxylic acid cycle (TCA) process for cellular energy production. a-KG mitigates cellular senescence, tissue degeneration, and oxidative stress. We investigated whether a-KG affected osteoblast activity or osteoporosis development.MethodSerum and bone specimens were biopsied from 26 patients with osteoporosis or 24 patients without osteoporosis who required spinal surgery. Ovariectomized or aged mice were fed 0.25% or 0.75% a-KG in drinking water for 8 – 12 weeks ad libitum. Bone mineral density, trabecular/cortical bone microarchitecture, mechanical strength, bone formation, and osteoclastic erosion were investigated using mCT, material testing device, in vivo calcein labelling, and TRAP histochemical staining. Serum a-KG, osteocalcin, and TRAP5b levels were quantified using ELISA kits. Bone-marrow mesenchymal cells and macrophages were incubated osteogenic and osteoclastogenic media. Histone H3K27me3 levels and enrichment were investigated using immunoblotting and chromatin precipitation-PCR.ResultSerum a-KG levels in patients with osteoporosis were less than controls; and were correlated with T-scores of hips (R2 = 0.6471, P < 0.0001) and lumbar spine (R2 = 0.7235, P < 0.001) in osteoporosis (AUC = 0.9941, P < 0.001). a-KG supplement compromised a plethora of osteoporosis signs in ovariectomized or aged mice, including bone mass loss, trabecular bone microarchitecture deterioration, and mechanical strength loss. It elevated serum osteocalcin levels and decreased serum TRAP5b. a-KG preserved caclein-labelling bone formation and repressed osteoclast resorption. It reversed osteogenic differentiation of bone-marrow stromal cells and reduced osteoclast formation in ovariectomized mice. Mechanically, a-KG attenuated H3K27 hypermethylation and Runx2 transcription repression, improving mineralized matrix production in osteogenic cells.ConclusionDecreased serum a-KG is correlated with human and murine osteoporosis. a-KG reverses bone loss by repressing histone methylation in osteoblasts. This study highlighted a-KG supplement as a new biochemical option for protecting osteoporosis.
BIOMECHANICAL ANALYSIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS: INVESTIGATING MUSCLE ACTIVATION ASYMMETRY DURING GAIT USING A COMPREHENSIVE THORACIC MUSCULOSKELETAL MODEL
Authors: Shayestehpour H. , Shayestehpour M. A. , Wong C. , Bencke J. , Rasmussen J. 
Published: November 2024

IntroductionAdolescent Idiopathic Scoliosis (AIS) is a three-dimensional deformity of the spine with unclear etiology. Due to the asymmetry of lateral curves, there are differences in the muscle activation between the convex and concave sides. This study utilized a comprehensive thoracic spine and ribcage musculoskeletal model to improve the biomechanical understanding of the development of AIS deformity and approach an explanation of the condition.MethodsIn this study, we implemented a motion capture model using a generic rigid-body thoracic spine and ribcage model, which is kinematically determinate and controlled by spine posture obtained, for instance, from radiographs. This model is publicly accessible via a GitHub repository. We simulated gait and standing models of two AIS (averaging 15 years old, both with left lumbar curve and right thoracic curve averaging 25 degrees) and one control subject. The marker set included extra markers on the sternum and the thoracic and lumbar spine. The study was approved by the regional Research Ethics Committee (Journal number: H17034237).ResultsWe investigated the difference between the muscle activation on the right and left sides including erector spinae (ES), psoas major (PS), and multifidus (MF). Results of the AIS simulations indicated that, on average throughout the gait cycle, the right ES, left PS and left MF had 46%, 44%, and 23% higher activities compared to the other side, respectively. In standing, the ratios were 28%, 40%, and 19%, respectively. However, for the control subject, the differences were under 7%, except ES throughout the gait, which was 17%.ConclusionThe musculoskeletal model revealed distinct differences in force patterns of the right and left sides of the spine, indicating an instability phenomenon, where larger curves lead to higher muscle activations for stabilization.AcknowledgementThe project is funded by the European Union's Horizon 2020 program through Marie Skłodowska-Curie grant No. [764644].
ROLE OF ALPHA-CGRP IN THE DEVELOPMENT OF POST-TRAUMATIC OSTEOARTHRITIS IN THE CONTEXT OF FORCED EXERCISE
Authors: Pann P. , Taheri S. , Schilling A. F. , Graessel S. 
Published: November 2024

IntroductionOsteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice.MethodOA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted.ResultOARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice.ConclusionOur results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects.
DOES THE ADDITION OF FLUORIDE TO BIOACTIVE GLASS AFFECT THE OSTEOGENIC AND ANGIOGENIC PROPERTIES OF BONE PROGENITOR CELLS?
Authors: Durach A. , Kunisch E. , Renkawitz T. , Westhauser F. , Brauer D. , Hohenbild F. 
Published: November 2024

IntroductionBioactive glasses (BGs) promote osteogenic differentiation of bone progenitor cells by releasing therapeutically active ions. The well-described 45S5-BG (in mol%: SiO2 46.13; P2O5 2.60; CaO 26.91; Na2O 24.35) was supplemented with CaF2 and NaF being added to the batch at nominal 5 (F5-BG) and 25 mol% (F25-BG), respectively. While the effect on physical and chemical properties has already been characterized, the biological properties require further studies. This study investigates the effects of fluoride-supplemented BGs on the osteogenic and angiogenic properties of human bone marrow mesenchymal stromal cells (BMSCs) in vitro.MethodBMSCs were co-cultured with melt-derived 45S5-BG, F5-BG, or F25-BG in ascending concentrations (1, 2 and 3 mg/ml). At 7 days, cell number was determined by 4,6-diamidine-2-phenylindole (DAPI) staining and cell viability by fluorescein diacetate (FDA) assay. The osteogenic potential of the BGs was evaluated through alkaline phosphatase (ALP) gene expression and activity, along with bone morphogenetic protein-2 (BMP2) gene expression and protein concentration. Vascular endothelial growth factor (VEGF) gene expression and protein concentration assessed angiogenic potential. As control, BMSCs were cultured without BG exposure.ResultAll BGs significantly promoted cell number and viability, with F25-BG showing the highest count at 3 mg/ml. Osteogenic markers showed a significant decrease in ALP gene expression and activity, especially at higher concentrations. All BG groups demonstrated increased BMP2 protein concentration and gene expression compared to the control, with higher BG and fluoride concentrations correlating with greater increases in BMP2. VEGF gene expression increased in all analysed BGs. The fluoride-free BG group had the highest VEGF protein concentrations, while the F25 BG group showed the highest VEGF gene expression.ConclusionThe fluoride-substituted BGs exhibit excellent cytocompatibility, enhance BMSC proliferation and positively affect BMP2 gene expression and levels, suggesting their potential for osteogenic differentiation. Further research is necessary to assess their proangiogenic effect and potential advantages over 45S5-BG.
MACROPHAGE-DERIVED EXTRACELLULAR VESICLES AS POTENTIAL MODULATORS OF TENDON INFLAMMATION
Authors: Cardona S. B. , Atanasov K. S. , Calvo J. , Gayà A. , Florit M. G. 
Published: November 2024

IntroductionTendinopathies represent a significant health burden, causing inflammation, pain, and reducing quality of life. The pivotal role of macrophages (Mφ) characterized by their ability to differentiate into proinflammatory (M1) or anti-inflammatory (M2) phenotypes depending on the microenvironment, has gained significant interest in tissue inflammation research. Additionally, existing literature states that the interplay between tenocytes and immune cells during inflammation involves unidentified soluble factors (SF). This study aimed to investigate the effect of extracellular vesicles (EVs) and SF derived from polarized Mφ on tendon cells to provide deeper insights of their potential therapeutic applications in the context of inflammation.MethodHuman monocytes were isolated from blood donor buffy coats and differentiated into M1, M2, and hybrid M1/M2 phenotypes. Subsequently, EVs were isolated from the conditioned media from polarized Mφ and comprehensively characterized. In parallel, the elution media containing SF was collected. Furthermore, the EVs and SF were released independently onto tenocytes from human donors, previously induced with IL-1β to simulate an inflammatory environment. Finally, mRNA levels of tendon-related markers were evaluated by qPCR after the exposure to these EVs and SF.ResultNotably, the study found that the viability of the cells was not affected by the exposure to EVs nor SF, indicating their potential safety for therapeutic use. Moreover, the mRNA content of tendon-derived cells was evaluated following exposure to Mφ-EVs and SF revealing alterations in gene expression. Interestingly, a significant increase in the expression of tenomodulin was observed in tendon cells treated with Mφ-EVs.ConclusionThese results mark a significant advancement in understanding the interplay between Mφ and tenocytes at a molecular level. To fully understand the underlying causes of Mφ-EVs effects, and its potential clinical application in tendon inflammatory diseases, further comprehensive research is required.AcknowledgmentsCarlos III Health Institute and the European Social Fund for contract CP21/00136 and project PI22/01686.
TRIAMCINOLONE: A MODULATOR OF CHONDROCYTE ELASTICITY AND MECHANOSENSITIVITY
Authors: Umrath F. , Liang C. , Jud S. , Alexander D. , Danalache M. 
Published: November 2024

IntroductionOsteoarthritis (OA) often results from joint misloading, which affects chondrocyte calcium signaling through mechano-sensitive receptors such as Piezo1, -2, and TRPV4. Activation of Piezo1, especially under inflammatory conditions, can trigger premature chondrocyte apoptosis. Intra-articular glucocorticoid therapy, while beneficial against inflammation and pain in osteoarthritis, may induce oxidative stress and chondrotoxicity at higher doses. This study aims to assess the effects of glucocorticoids, particularly triamcinolone, on chondrocyte elasticity and mechanosignaling.MethodChondrocytes isolated from articular condyles obtained from patients undergoing knee replacement surgery (n= 5) were cultured for 7 days in triamcinolone acetonide (TA) at different concentrations (0.2µM – 2mM). Cytoskeletal changes were assessed by F-actin labeling. Cell elasticity was measured using atomic force microscopy (AFM). Labeling cells (n=6 patients) with the calcium-sensitive dye (Fluo-4) enabled monitoring changes in intracellular calcium fluorescence intensity during guided single-cell mechanical indentation (500 nN) by AFM.ResultCell exposure to 2 mM TA led to cell death and crystallization of TA in the cell culture media. However, the concentration of TA for intra-articular application is 46 times higher at 92.1 mM (40 mg/ml). The maximal pharmacological effect on viable cells was observed at 0.2 mM. AFM results showed a significant decrease of elasticity (p<0.001), alongside significantly higher calcium intensities both prior to and during mechanical stimulation in the TA-treated samples (p<0.05).ConclusionAdministration of TA significantly impacts the mechanical properties of chondrocytes, reducing cellular elasticity while simultaneously enhancing calcium-dependent mechanosensitivity. This data suggests a correlation between glucocorticoid-induced changes in cell elasticity and cell mechanosensitivity. Finding ways to minimize the effect of glucocorticoids on cell mechanosensitivity could help to make future therapies safer and reduce side effects.
CAN 3D PLANNING HELP OPTIMIZE FEMORAL HEAD COVERAGE IN PERIACETABULAR OSTEOTOMY?
Authors: Thakur A. , Harris S. , Brkljač M. , Cobb J. , Logishetty K. 
Published: November 2024

IntroductionBernese periacetabular osteotomy (PAO) repositions the acetabulum to increase femoral head coverage (FHC) in hip dysplasia. Currently, there is a paucity of objective peri-operative metrics to plan for optimal acetabular fragment repositioning. The MSk Lab Hip 3D Planner (MSkL-HP) measures acetabular morphology and simulates PAO cuts to achieve optimal FHC. We evaluated how adjusting location and orientation of cutting planes can alter FHC.MethodMSkL-HP simulated 274 feasible PAOs on four dysplastic hips. Femoroacetabular anatomy was landmarked to simulate cutting planes. Posterior column and ischial cuts were standardised, whilst iliac and pubic cut combinations varied. The slope of the iliac cut was either neutral (aligned to pelvis), exit point 5mm above the entry point (+5), or 5mm below (-5). The slope of the pubic cut was either 90°, 50°, or 70° (medial-to-lateral). Iliac and pubic cuts were simulated 0, 5 and 15mm - distal and medial – to a classic cut. Outcome measures were achieved LCEA, Tönnis, FHC and % bone overlap at the pubic cut. Targets were LCEA >30°, Tönnis angle <10°, and FHC >70% and minimum bone overlap ≥10%.ResultsAll feasible PAOs resulted in improvement from pre-operative metrics. Personalised cutting planes provided greater benefit than standard planes. Kruskal Wallis tests showed that the iliac cut at 5mm or 15mm resulted in a greater LCEA and lower Tönnis compared to the classic cut (p<0.05). Changing location of the pubic cut, and slope of the iliac and pubic cuts did not significantly affect LCEA and Tönnis in all hips (p<0.05). Cut combinations optimising metrics were associated with a lower % pubic cut overlap.ConclusionMSkL-HP feasibly and reliably planned personalised PAO, measuring pre-operative and simulated post-operative objective metrics. Patient-specific pubic and iliac cuts enable greater correction whilst maintaining bone overlap. Further simulations on patients with varying morphology may improve standard techniques.
SAFETY AND PERFORMANCE OF DEXTRAN-TYRAMINE HYDROGEL IMPLANT FOR FOCAL ARTICULAR CARTILAGE LESIONS OF THE KNEE (ACTIVE): PRELIMINARY DATA OF THE SAFETY COHORT
Authors: Weiden G. V. D. , Egmond N. V. , Karperien M. , Both S. , Mastbergen S. , Emans P. , Caron J. , Custers R. 
Published: November 2024

IntroductionThe ACTIVE(Advanced Cartilage Treatment with Injectable-hydrogel Validation of the Effect) study investigates safety and performance of a novel dextran-tyramine hydrogel implant for treatment of small cartilage defects in the knee (0.5-2.0cm2). The hydrogel is composed of a mixture of natural polymer conjugates that are mixed intra-operatively and which cross-link in situ through a mild enzymatic reaction, providing a cell-free scaffold for cartilage repair.MethodThe ACTIVE study is split into a safety (n=10) and a performance cohort (n=36). The Knee Injury and Osteoarthritis Outcome Score (KOOS), pain (numeric rating scale, NRS), Short-Form Health Survey (SF-36) were compared at baseline and 3, 6, and 12 months after surgery. The primary performance hypothesis is an average change in the KOOS from baseline to 12 months (ΔKOOS) greater than a minimal clinically important change (MIC) of 10. No statistical tests were performed as these are preliminary data on a smaller portion of the total study.ResultAll patients of the safety cohort (n=10, mean age±SD, 30±9 years) were treated with the hydrogel for a symptomatic (NRS≥4) cartilage defect on the femoral condyle or trochlear groove (mean size±SD, 1.2±0.4cm2). No signs of an adverse foreign tissue reaction or serious adverse events were recorded within the safety cohort. At final follow-up mean KOOS±SD was 66.9±23.5, mean NRS resting±SD was 1.3±1.9, NRS activity±SD was 3.8±2.9 and mean SF-36±SD was 72.0±10.9. ΔKOOS was 21. One patient sustained new knee trauma prior to final follow-up, affecting final scores considerably. When excluded, ΔKOOS was 24(n=9).ConclusionThese promising initial findings provide a solid basis for continuation and expansion of this unique cartilage treatment. The MIC of 10 was surpassed. Though, results should be interpreted cautiously as they are based solely on preliminary data of the first 10 patients.AcknowledgementsStudy is sponsored by Hy2Care, producer of the CartRevive®(dextran-tyramine) Hydrogel implant.