bluuebunny/crossref_metadata_2025_split huggingface dataset:
IN VIVO KINEMATICS DURING STEP ASCENT IN THREE TOTAL KNEE ARTHROPLASTY DESIGNS: A RANDOMIZED CLINICAL TRIAL
Authors: Lynch J. , Perriman D. , Scarvell J. , Pickering M. , Galvin C. , Smith P. 
Published: July 2023

Total knee replacement (TKR) design aims to restore normal kinematics with emphasis on flexion range. The survivorship of a TKR is dependent on the kinematics in six-degrees-of-freedom (6-DoF). Stepping up, such as stair ascent is a kinematically demanding activity after TKR. The debate about design choice has not yet been informed by 6-DoF in vivo kinematics. This prospective randomised controlled trial (RCT) compared kneeling kinematics in three TKR designs.68 participants were randomised to receive either cruciate retaining (CR-FB), rotating platform (CR-RP) or posterior stabilised (PS-FB) prostheses. Image quality was sufficient for 49 of these patients to be included in the final analysis following a minimum 1-year follow-up. Patients completed a step-up task while being imaged using single-plane fluoroscopy. Femoral and tibial computer-aided design (CAD) models for each of the TKR designs were registered to the fluoroscopic images using bespoke software OrthoVis to generate six-degree-of-freedom kinematics. Differences in kinematics between designs were compared as a function of flexion.There were no differences in terminal extension between the groups. The CR-FB was further posterior and the CR-RP was more externally rotated at terminal extension compared to the other designs. Furthermore, the CR-FB designs was more posteriorly positioned at each flexion angle compared to both other designs. Additionally, the CR-RP design had more external femoral rotation throughout flexion when compared with both fixed bearing designs. However, there were no differences in total rotation for either step-up or down. Visually, it appears there was substantial variability between participants in each group, indicating unique patient-specific movement patterns.While use of a specific implant design does influence some kinematic parameters, the overall patterns are similar. Furthermore, there is high variability indicating patient-specific kinematic patterns. At a group level, none of these designs appear to provide markedly different step-up kinematic patterns. This is important for patient expectations following surgery. Future work should aim to better understand the unique patient variability.
IN VIVO PILOT STUDY OF TIBIOFEMORAL KINEMATICS DURING LOADED DYNAMIC ACTIVITIES
Authors: Swain L. , Shillabeer D. , Wyatt H. , Jonkers I. , Holt C. , Williams D. 
Published: July 2023

Biplane video X-ray (BVX) – with models segmented from magnetic resonance imaging (MRI) – is used to directly track bones during dynamic activities. Investigating tibiofemoral kinematics helps to understand effects of disease, injury, and possible interventions.Develop a protocol and compare in-vivo kinematics during loaded dynamic activities using BVX and MRI.BVX (60 FPS) was captured whilst three healthy volunteers performed three repeats of lunge, stair ascent and gait. MRI scans were performed (Magnetom 3T Prisma, Siemens). 3D bone models of the tibia and femur were segmented (Simpleware Scan IP, Synopsis). Bone poses were obtained by manually matching bone models to X-rays (DSX Suite, C-Motion Inc.). Mean range of motion (ROM) of the contact points on the medial and lateral tibial plateau were calculated using custom MATLAB code (MathWorks). Results were filtered using an adaptive low pass Butterworth filter (Frequency range: 5-29Hz).Gait and Stair ascent activities from one participant's data showed increased ROM for medial-lateral (ML) translation in the medial compartment but decreased ROM in anterior-posterior (AP) translation when comparing against the same translations on the lateral compartment of the tibial plateau. Lunge activity showed increased ROM for both ML and AP translation in the medial compartment when compared with the lateral compartment.These results highlight the variability in condylar translations between different activities. Understanding healthy in-vivo kinematics across different activities allows the determination of suitable activities to best investigate the kinematic changes due to disease or injury and assess the efficacy of different interventions.Acknowledgements: This research was supported by the Engineering and Physical Sciences Research Council (EPSRC) doctoral training grant (EP/T517951/1).
MEASURING OSTEOARTHRITIS KNEE NOCICEPTION USING PHYSIOLOGICAL AND MOVEMENT RESPONSES AND A DEFINED THERMAL STIMULUS: A PROOF OF CONCEPT STUDY
Authors: Hamilton R. , Holt C. , Hamilton D. , Garcia A.A. , Graham C. , Jones R. , Shilabeer D. , Kuiper J.H. , Sparkes V. , Khot S. , Mason D. 
Published: July 2023

Mechanical loading of joints with osteoarthritis (OA) results in pain-related functional impairment, altered joint mechanics and physiological nociceptor interactions leading to an experience of pain. However, the current tools to measure this are largely patient reported subjective impressions of a nociceptive impact. A direct measure of nociception may offer a more objective indicator. Specifically, movement-induced physiological responses to nociception may offer a useful way to monitor knee OA. In this study, we gathered preliminary data on healthy volunteers to analyse whether integrated biomechanical and physiological sensor datasets could display linked and quantifiable information to a nociceptive stimulus.Following ethical approval, 15 healthy volunteers completed 5 movement and stationary activities in 2 conditions; a control setting and then repeated with an applied quantified thermal pain stimulus to their right knee. An inertial measurement unit (IMU) and an electromyography (EMG) lower body marker set were tested and integrated with ground reaction force (GRF) data collection. Galvanic skin response electrodes for skin temperature and conductivity and photoplethysmography (PPG) sensors were manually timestamped to the integrated system.Pilot data showed EMG, GRF and IMU fluctuations within 0.5 seconds of each other in response to a thermal trigger. Preliminary analysis on the 15 participants tested has shown skin conductance, PPG, EMG, GRFs, joint angles and kinematics with varying increases and fluctuations during the thermal condition in comparison to the control condition.Preliminary results suggest physiological and biomechanical data outputs can be linked and identified in response to a defined nociceptive stimulus. Study data is currently founded on healthy volunteers as a proof-of-concept. Further exploratory statistical and sensor readout pattern analysis, alongside early and late-stage OA patient data collection, can provide the information for potential development of wearable nociceptive sensors to measure disease progression and treatment effectiveness.
EXCESSIVE WNT SIGNALLING ALTERS THE CARTILAGE RESPONSE TO PHYSIOLOGIC LOADING
Authors: Castro-Viñuelas R. , Viudes-Sarrión N. , Monteagudo S. , Lories R. , Jonkers I. 
Published: July 2023

Regulation of articular cartilage homeostasis is a complex process in which biologic and mechanical factors are involved. Hyperactivation of Wnt signaling, associated with osteoarthritis (OA), could jeopardize the protective anabolic effect of physiological loading. Here, we investigated the role of excessive Wnt signalling in cartilage molecular responses to loading.Human cartilage explants were harvested from hips of donors without OA. The Wnt agonist CHIR99021 was used to activate Wnt signalling 24 hours before cartilage explants were subjected to a loading protocol consisting of 2 cycles of 1 hour of 10% compression at 1 Hz, followed by 1-hour free swelling. Mechano-responsiveness was evaluated using the expression of type II collagen, aggrecan and MMP-13. Expression of known target genes TCF-1 and c-JUN was evaluated as positive control for Wnt and mechanical stimulation, respectively.In the absence of loading, CHIR99021 decreased the expression of the cartilage anabolic genes type II collagen and aggrecan, and increased the levels of MMP-13, corroborating that Wnt hyperactivation disrupts cartilage homeostasis. In the absence of Wnt hyperactivation, the applied loading protocol, representative for a physiologic stimulation by mechanical loading, led to an increase in type II collagen and aggrecan levels. However, when cartilage explants were subjected to mechanical stimulation in the presence of CHIR99021, the expression of cartilage anabolic genes was decreased, indicating changes to the cells’ mechano-responsiveness. Interestingly, mechanical stimulation was able to reduce the expression levels of MMP-13 compared to the condition of CHIR stimulation without loading.Hyperactivation of Wnt signaling switches the anabolic effect of physiologic compressive loading towards a potential catabolic effect and could contribute to the development and progression of OA.
IMPACT OF CLINICAL COMMUNICATION SUMMARY REPORT ON INJURED WORKERS’ SATISFACTION FOLLOWING ROTATOR CUFF SURGERY
Authors: Boljanovic D. , Razmjou H. 
Published: July 2023

The purpose of the this survey study was twofold: 1) to examine different aspects of satisfaction with post-operative care in injured workers who have undergone rotator cuff surgery and 2) to examine the relationship between receiving a newly implemented summary report and the overall satisfaction with surgery and recovery.The clinical communication summary report was given to injured workers following their review assessment to share with the family doctor or other health care providers. The form indicated a need for further assessments or investigations and return to work recommendations. The study involved using a satisfaction survey that examined different aspects of follow-up visit and workers’ opinion about their understanding of the nature of surgery, their progress, clinical management, and usefulness of the newly implemented summery report.Eighty patients completed the questionnaire (mean age: 54 (8), 62(78%) males, of whom 26 (34%) had a rotator cuff decompression and 31 (40%) had a rotator cuff repair with 20 (26%) having both procedures and three missing data. There were no statistically significant relationships between the patient demographics (age, sex or type of surgery) and satisfaction. However, there was a significant correlation between how patients perceived the summary report in terms of helpfulness and the overall satisfaction with surgery (FTE<0.0004, p=0.001) and the satisfaction with recovery (FTE<0.0001, p=0.001). This may indicate that improvement in worker's understanding of their treatment recommendations and restrictions is associated with higher levels of overall satisfaction in this population.Our results indicate a positive linear relationship between expressing a high satisfaction and the helpfulness of the summary report. As part of improving care, adding a summary report may facilitate sharing information with the injured workers, their care providers and their workplace.
AUTOMATIC SEGMENTATION AND BONE ARCHITECTURE ANALYSIS OF SUBCHONDRAL BONE IN THE MURINE PROXIMAL TIBIA: EVALUATION OF AN OPEN-SOURCE PIPELINE
Authors: Mahdi H. , Hardisty M. , Fullerton K. , Huang C. , Vachhani K. , Nam D. , Whyne C. 
Published: July 2023

µCT images are commonly analysed to assess changes in bone density and architecture in preclinical murine models. Several platforms provide automated analysis of bone architecture parameters from volumetric regions of interest (ROI). However, segmentation of the regions of subchondral bone to create the volumetric ROIs remains a manual and time-consuming task. This study aimed to develop and evaluate automated pipelines for trabecular bone architecture analysis of mouse proximal tibia subchondral bone.A segmented dataset involving 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice were used to train a U-Net type architecture, with µCT scans (downsampled) input that output segmentation and bone volume density (BV/TV) of the subchondral trabecular bone. Segmentations were upsampled and used in tandem with the original scans (10µ) as input for architecture analysis along with the thresholded trabecular bone. The analysis considered the manually and U-Net segmented ROIs using two available pipelines: the ITKBoneMorphometry library and CTan (SKYSCAN). The analyses included: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV).There was good agreement for bone measures between the manual and U-Net pipelines utilizing ITK (R=0.88-0.98) and CTan (R=0.91-0.98). ITK and CTan showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R=0.9-0.98). However, a limited agreement was seen between TbN (R=0.73) and TbSb (R=0.59) due to methodological differences in how spacing is evaluated.This U-Net/ITK pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of stereologic analysis of trabecular bone across different research groups.
ENGINEERED EXTRACELLULAR MATRIX ENHANCES THE BONE REGENERATION POTENTIAL OF AGED HUMAN BONE MARROW STROMAL CELLS
Authors: Hanetseder D. , Hruschka V. , Redl H. , Marolt Presen D. 
Published: July 2023

Regeneration of bone defects in elderly patients is limited due to the decreased function of bone forming cells and compromised tissue physiology. Previous studies suggested that the regenerative activity of stem cells from aged tissues can be enhanced by exposure to young systemic and tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells (hiPSCs) can enhance the bone regeneration potential of aged human bone marrow stromal cells (hBMSCs).ECM was engineered from hiPSC-derived mesenchymal-like progenitors (hiPSC-MPs), as well as young (<30 years) and aged (>70 years) hBMSCs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. Three hBMSCs of different ages were cultured on engineered ECMs. Growth and differentiation responses were compared to tissue culture plastic, as well as to collagen and fibronectin coated plates.Decellularized ECMs contained collagens type I and IV, fibronectin, laminin and < 5% residual DNA, suggesting efficient cell elimination. Cultivation of young and aged hBMSCs on the hiPSC-ECM in osteogenic medium significantly increased hBMSC growth and markers of osteogenesis, including collagen deposition, alkaline phosphatase activity, bone sialoprotein expression and matrix mineralization compared to plastic controls and single protein substrates. In aged BMSCs, matrix mineralization was only detected in ECM cultures in osteogenic medium. Comparison of ECMs engineered from hiPSC-MPs and hBMSCs of different ages suggested similar structure, composition and potential to enhance osteogenic responses in aged BMSCs. Engineered ECM induced a higher osteogenic response compared to specific matrix components.Our studies suggest that aged BMSCs osteogenic activity can be enhanced by culture on engineered ECM. hiPSCs represent a scalable cell source, and tissue engineering strategies employing engineered ECM materials could potentially enhance bone regeneration in elderly patients.
CHARACTERIZATION OF MESENCHYMAL STROMAL CELL EXTRACELLULAR VESICLE RELEASE PROFILES AND CARGO: RELEVANCE FOR BONE REGENERATIVE THERAPIES
Authors: Richter F. , Oesterreicher J. , Goeschl V. , Hanetseder D. , Hackl M. , Pultar M. , Redl H. , Grillari J. , Holnthoner W. , Marolt Presen D. 
Published: July 2023

Recent studies suggested that both the soluble protein of the mesenchymal stromal cell (MSC) secretome, as well as the secreted extracellular vesicles (EVs) promote bone regeneration. However, there is limited knowledge of the changes in MSC secretome vesicular fraction during aging. We therefore aimed to characterize the release profiles and cargo of EVs from MSCs of different chronological ages.Conditioned medium (CM) was collected from 13 bone marrow MSC strains (20-89 years) and from one MSC strain derived from human induced pluripotent stem cells (iPSCs). The EV-containing fraction was enriched with ultracentrifugation. The number of particles in the CM was evaluated by nanoparticle tracking analysis (NTA), and the number of EVs was evaluated by flow cytometry (FC) after staining with cell-mask-green and anti-CD81 antibody. EV cargo analysis was conducted using next-generation sequencing (NGS).Our data confirmed the release of EVs from all MSC strains used in the study. There were no correlations between the number of particles and the number of EVs released in the CM, and between the number of EVs released and the strain age. Nevertheless, some of the lowest concentrations of EVs were found in the CM of strains over 70 years of age, which exhibited a low/absent chondrogenic and osteogenic differentiation potential. In contrast, iPSC-MSCs, which exhibited a high growth and three-lineage differentiation potential, released a similar amount of EVs as the best performing bone marrow MSC strain. NGS analysis identified several microRNAs that were significantly enriched in EVs of young MSC strains exhibiting low senescence, and those that were enriched in EVs of strains exhibiting high differentiation potentials. Gender had no influence on microRNA profiles in EVs or releasing MSCs.Taken together, our data provides new insights into the properties of MSC vesicular secretome and its therapeutic potential during aging.
DOES BONE TURNOVER EXPLAIN HIGH BONE DENSITY IN FEMOROACETABULAR IMPINGEMENT? AN ANALYSIS OF PET AND CT IMAGING
Authors: Speirs A. , Melkus G. , Rakhra K. , Beaule P. 
Published: July 2023

Femoroacetabular impingement (FAI) results from a morphological deformity of the hip and is associated with osteoarthritis (OA). Increased bone mineral density (BMD) is observed in the antero-superior acetabulum rim where impingement occurs. It is hypothesized that the repeated abnormal contact leads to damage of the cartilage layer, but could also cause a bone remodelling response according to Wolff's Law. Thus the goal of this study was to assess the relationship between bone metabolic activity measured by PET and BMD measured in CT scans.Five participants with asymptomatic cam deformity, three patients with uni-lateral symptomatic cam FAI and three healthy controls were scanned in a 3T PET-MRI scanner following injection with [18F]NaF. Bone remodelling activity was quantified with Standard Uptake Values (SUVs). SUVmax was analyzed in the antero-superior acetabular rim, femoral head and head-neck junction. In these same regions, BMD was calculated from CT scans using the calibration phantom included in the scan. The relationship between SUVmax and BMD from corresponding regions was assessed using the coefficient of determination (R2) from linear regression.High bone activity was seen in the cam deformity and acetabular rim. SUVmax was negatively correlated with BMD in the antero-superior region of the acetabulum (R2=0.30, p=0.08). SUVmax was positively correlated with BMD in the antero-superior head-neck junction of the femur (R2=0.359, p=0.067). Correlations were weak in other regions.Elevated bone turnover was seen in patients with a cam deformity but the relationship to BMD was moderate. This study demonstrates a pathomechanism of hip degeneration associated with FAI deformities, consistent with Wolff's law and the proposed mechanical cause of hip degeneration in FAI. [18F]-NaF PET SUV may be a biomarker of degeneration, especially in early stages of degeneration, when joint preservation surgery is likely to be the most successful.
EX VIVO ORGAN MODEL AND SAMPLE HOLDER FOR INTERVERTEBRAL DISC STUDIES IN A NEW GENERATION OF MULTIAXIAL BIOREACTORS
Authors: Šećerović A. , Ristaniemi A. , Cui S. , Li Z. , Alini M. , Weder G. , Heub S. , Ledroit D. , Grad S. 
Published: July 2023

A novel ex vivo intervertebral disc (IVD) organ model and corresponding sample holder were developed according to the requirements for six degrees of freedom loading and sterile culture in a new generation of multiaxial bioreactors. We tested if the model can be maintained in long-term IVD organ culture and validated the mechanical resistance of the IVD holder in compression, tension, torsion, and bending.An ex vivo bovine caudal IVD organ model was adapted by retaining 5-6 mm of vertebral bone to machine a central cross and a hole for nutrient access through the cartilaginous endplate. A counter cross was made on a customized, circular IVD holder. The new model was compared to a standard model with a minimum of bone for the cell viability and height changes after 3 weeks of cyclic compressive uniaxial loading (0.02-0.2 MPa, 0.2 Hz, 2h/ day; n= 3 for day 0, n= 2 for week 1, 2, and 3 endpoints). Mechanical tests were conducted on the assembly of IVD and holder enhanced with different combinations of side screws, top screws, and bone adhesive (n=3 for each test).The new model retained a high level of cell viability after three weeks of in vitro culture (outer annulus fibrosus 82%, inner annulus fibrosus 69%, nucleus pulposus 75%) and maintained the typical values of IVD height reduction after loading (≤ 10%). The holder-IVD interface reached the following highest average values in the tested configurations: 320.37 N in compression, 431.86 N in tension, 1.64 Nm in torsion, and 0.79 Nm in bending.The new IVD organ model can be maintained in long-term culture and when combined with the corresponding holder resists sufficient loads to study IVD degeneration and therapies in a new generation of multiaxial bioreactors.