bluuebunny/crossref_metadata_2025_split huggingface dataset:
CHRONOLOGICAL AGE AFFECTS MSC SENESCENCE IN VITRO: A SYSTEMATIC REVIEW
Authors: Kapetanos K. , Asimakopoulos D. , Christodoulou N. , Vogt A. , Khan W. 
Published: July 2023

The use of mesenchymal stromal cells (MSCs) in regenerative medicine and tissue engineering is well established, given their properties of self-renewal and differentiation. However, several studies have shown that these properties diminish with age, and understanding the pathways involved are important to provide regenerative therapies in an ageing population.In this PRISMA systematic review, we investigated the effects of chronological donor ageing on the senescence of MSCs. We identified 3023 studies after searching four databases including PubMed, Web of Science, Cochrane, and Medline. Nine studies met the inclusion and exclusion criteria and were included in the final analyses.These studies showed an increase in the expression of p21, p53, p16, ROS, and NF- B with chronological age. This implies an activated DNA damage response (DDR), as well as increased levels of stress and inflammation in the MSCs of older donors. Additionally, highlighting the effects of an activated DDR in cells from older donors, a decrease in the expression of proliferative markers including Ki67, MAPK pathway elements, and Wnt/ -catenin pathway elements was observed. Furthermore, we found an increase in the levels of SA- -galactosidase, a specific marker of cellular senescence.Together, these findings support an association between chronological age and MSC senescence. The precise threshold for chronological age where the reported changes become significant is yet to be defined and should form the basis for further scientific investigations. The outcomes of this review should direct further investigations into reversing the biological effects of chronological age on the MSC senescence phenotype.
SMALL NON-CODING RNA LANDSCAPE OF EXTRACELLULAR VESICLES FROM AN EXPERIMENTAL MODEL OF EQUINE OSTEOARTHRITIS
Authors: Peffers M. , Anderson J. , Jacobsen S. , Walters M. , Bundgaard L. , Hackle M. , James V. 
Published: July 2023

Joint tissues release extracellular vesicles (EVs) that potentially sustain joint homeostasis and contribute to osteoarthritis (OA) pathogenesis. EVs are putative novel therapeutics for OA, and transport biologically active molecules (including small non-coding RNAs (SNCRNAs)) between cells. This study identified altering SNCRNA cargo in EVs in OA which may act as early diagnostic markers and treatment targets.OA was surgically induced in four skeletally mature Standardbred horses using an osteochondral fragment model in the left middle carpal joint. The right joint underwent sham surgery. Synovial fluid (SF) and plasma were obtained weekly throughout the 70-day study. EVs were isolated using size exclusion chromatography and characterised using nanoparticle tracking (Nanosight), and exosome fluorescence detection and tetraspanin phenotyping (Exoview). RNA was extracted from EVs derived from SF (sham and OA joints) and plasma collected at days 10, 35, 42, 49, 56, 63, and subjected to small RNA sequencing on a NovaSeq SP100 flow cell (Illumina).Nanosight-derived EV characteristics of size and concentration were not significantly different following disease induction. The diameter of the temporal population of plasma and SF-derived exosomes changed significantly for CD9 and CD81 following OA induction with significant temporal, and disease-related changes in CD63 and CD81 protein expressin in plasma and SF.In SF and plasma-derived EVs snoRNAs, snRNAs, tRNAs, lncRNA, y-RNA, piRNAs and scRNA were found. Following pairwise analysis of all-time points we identified 27 miRs DE in plasma and 45 DE miRs in SF. Seven were DE in plasma and SF; miR-451, miR-25, miR-215, miR-92a, miR-let-7c, miR-486-5p, miR-23a. In plasma and SF 35 and 21 snoRNAs were DE with four DE in plasma and SF; U3, snord15, snord46, snord58.This work has identified alterations to OA EV sncRNAs in plasma and SF providing a greater understanding of the role of EVs in early OA.
THREE-DIMENSIONAL KINEMATICS OF THE JAW FOLLOWING UNILATERAL AND BILATERAL PROSTHETIC TMJ SURGERY
Authors: Woodford S. , Robinson D. , Lee P. , Abduo J. , Dimitroulis G. , Ackland D. 
Published: July 2023

Total temporomandibular joint (TMJ) replacements reduce pain and improve quality of life in patients suffering from end-stage TMJ disorders, such as osteoarthritis and trauma. Jaw kinematics measurements following TMJ arthroplasty provide a basis for evaluating implant performance and jaw function. The aim of this study is to provide the first measurements of three-dimensional kinematics of the jaw in patients following unilateral and bilateral prosthetic TMJ surgeries.Jaw motion tracking experiments were performed on 7 healthy control participants, 3 unilateral and 1 bilateral TMJ replacement patients. Custom-made mouthpieces were manufactured for each participant's mandibular and maxillary teeth, with each supporting three retroreflective markers anterior to the participant's lip line. Participants performed 15 trials each of maximum jaw opening, lateral and protrusive movements. Marker trajectories were simultaneously measured using an optoelectronic tracking system. Laser scans taken of each dental plate, together with CT scans of each patient, were used to register the plate position to each participant's jaw geometry, allowing 3D condylar motion to be quantified from the marker trajectories.The maximum mouth opening capacity of joint replacement patients was comparable to healthy controls with average incisal inferior translations of 37.5mm, 38.4mm and 33.6mm for the controls, unilateral and bilateral joint replacement patients respectively. During mouth opening the maximum anterior translation of prosthetic condyles was 2.4mm, compared to 10.6mm for controls. Prosthetic condyles had limited anterior motion compared to natural condyles, in unilateral patients this resulted in asymmetric opening and protrusive movements and the capacity to laterally move their jaw towards their pathological side only. For the bilateral patient, protrusive and lateral jaw movement capacity was minimal.Total TMJ replacement surgery facilitates normal mouth opening capacity and lateral and inferior condylar movements but limits anterior condylar motion. This study provides future direction for TMJ implant design.
DNA METHYLATION AND ITS INFLUENCE ON THE PATHOGENESIS OF OSTEOARTHRITIS: A SYSTEMATIC LITERATURE REVIEW
Authors: Nau T. , Cutts S. , Naidoo N. 
Published: July 2023

There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA.A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers.During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage.This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available.
A RETROSPECTIVE SINGLE-CENTRE STUDY DEMONSTRATING HOW DIFFERENT KIRSCHNER WIRE CONFIGURATION FOR BASE OF FOURTH AND FIFTH METACARPAL FRACTURES CAN INFLUENCE COMPLICATION RATES
Authors: Biddle M. , Wilson V. , Miller N. , Phillips S-A. 
Published: July 2023

Our aim was to ascertain if K-wire configuration had any influence on the infection and complication rate for base of 4th and 5th metacarpal fractures. We hypothesised that in individuals whose wires crossed the 4th and 5th carpometacarpal joint (CMCJ), the rate of complications and infection would be higher.Data was retrospectively analysed from a single centre. 106 consecutive patients with a base of 5th (with or without an associated 4th metacarpal fracture) were analysed between October 2016 and May 2021. Patients were split into two groups for comparison; those who did not have K-wires crossing the CMCJ's and those in whose fixation had wires crossing the joints. Confounding factors were accounted for and Statistical analysis was performed using SPSS version 20 software.Of 106 patients, 60 (56.6%) patients did have K-wires crossing the CMCJ. Wire size ranged from 1.2-2.0 with 65 individuals (65.7%) having size 1.6 wires inserted. The majority of patients, 66 (62.9%) underwent fixation with two wires (range 1-4). The majority of infected cases (88.9%) were in patients who had k-wires crossing the CMCJ, this trended towards clinical significance (p=0.09). Infection was associated with delay to theatre (p=0.002) and longer operative time (p=0.002).In patients with a base of 4th and 5th metacarpal fractures, we have demonstrated an increased risk of post-operative infection with a K-wire configuration that crosses the CMCJ. Biomechanical studies would be of use in determining the exact amount of movement across the CMCJ, with the different K-wire configuration in common use, and this will be part of a follow-up study.
SURGICAL TECHNIQUE AND COMPARISON OF AUTOLOGOUS CANCELLOUS BONE GRAFTS FROM VARIOUS DONOR SITES IN RATS
Authors: Gens L. , Marchionatti E. , Steiner A. , Stoddart M. , Thompson K. , Mys K. , Zeiter S. , Constant C. 
Published: July 2023

Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft.13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4).It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells.The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study.
RETHINKING THE 10% RULE: PATIENT-SPECIFIC MODELLING OF STRAIN IN DISTAL FEMUR FRACTURES
Authors: Inacio J. , Schwarzenberg P. , Yoon R. , Kantzos A. , Malige A. , Nwachuku C. , Dailey H. 
Published: July 2023

The objective of this study was to use patient-specific finite element modeling to measure the 3D interfragmentary strain environment in clinically realistic fractures. The hypothesis was that in the early post-operative period, the tissues in and around the fracture gap can tolerate a state of strain in excess of 10%, the classical limit proposed in the Perren strain theory.Eight patients (6 males, 2 females; ages 22–95 years) with distal femur fractures (OTA/AO 33-A/B/C) treated in a Level I trauma center were retrospectively identified. All were treated with lateral bridge plating. Preoperative computed tomography scans and post-operative X-rays were used to create the reduced fracture models. Patient-specific materials properties and loading conditions (20%, 60%, and 100% body weight (BW)) were applied following our published method.[1]Elements with von Mises strains >10% are shown in the 100% BW loading condition. For all three loading scenarios, as the bridge span increased, so did the maximum von Mises strain within the strain visualization region. The average gap closing (Perren) strain (mean ± SD) for all patient-specific models at each body weight (20%, 60%, and 100%) was 8.6% ± 3.9%, 25.8% ± 33.9%, and 39.3% ± 33.9%, while the corresponding max von Mises strains were 42.0% ± 29%, 110.7% ± 32.7%, and 168.4% ± 31.9%. Strains in and around the fracture gap stayed in the 2–10% range only for the lowest load application level (20% BW).Moderate loading of 60% BW and above caused gap strains that far exceeded the upper limit of the classical strain rule (<10% strain for bone healing). Since all of the included patients achieved successful unions, these findings suggest that healing of distal femur fractures may be robust to localized strains greater than 10%.
SMART BIOACTIVE PERSONALIZED AND IMPLANTABLE 3D-PRINTED SCAFFOLD FOR TENDON REGENERATION: PRELIMINARY RESULTS OF TRITONE PROJECT
Authors: Andreani L. , Vozzi G. , Petrini M. , Di Stefano R. , Trincavelli M.L. , Mani O. , Olivieri M. , Bizzocchi F. , Creati G. , Capanna R. 
Published: July 2023

Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue.Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors.Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria.Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold.These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step.
DIFFERENCES IN THE CONTRIBUTION OF EACH LOWER LIMB IN THE DROP VERTICAL JUMP TASK SHOULD BE ASSESSED IN ANTERIOR CRUCIATE LIGAMENT-INJURED PAEDIATRIC POPULATION
Authors: Hornestam J.F. , Miller B. , Carsen S. , Benoit D. 
Published: July 2023

To investigate differences in the drop vertical jump height in female adolescents with an ACL injury and healthy controls and the contribution of each limb in this task.
Forty female adolescents with an ACL injury (ACLi, 15.2 ± 1.4 yrs, 164.6 ± 6.0 cm, 63.1 ± 10.0 kg) and thirty-nine uninjured (CON, 13.2 ± 1.7 yrs, 161.7 ± 8.0 cm, 50.6 ± 11.0 kg) were included in this study. A 10-camera infrared motion analysis system (Vicon, Nexus, Oxford, UK) tracked pelvis, thigh, shank, and foot kinematics at 200Hz, while the participants performed 3 trials of double-legged drop vertical jumps (DVJ) on two force plates (Bertec Corp., Columbus, USA) sampled at 2000Hz.The maximum jump height normalised by dominant leg length was compared between groups using independent samples t-test. The maximum vertical ground reaction force (GRFz) and sagittal ankle, knee and hip velocities before take-off were compared between limbs in both groups, using paired samples t-test.
The normalised jump height was 11% lower in the ACLi than in the CON (MD=0.04 cm, p=0.020). In the ACLi, the maximum GRFz (MD=46.17N) and the maximum velocities of ankle plantar flexion (MD=79.83°/s), knee extension (MD=85.80°/s), and hip extension (MD=36.08°/s) were greater in the non-injured limb, compared to the injured limb. No differences between limbs were found in the CON.ACL injured female adolescents jump lower than the healthy controls and have greater contribution of their non-injured limb, compared to their injured limb, in the DVJ task. Clinicians should investigate differences in the contribution between limbs during double-legged drop vertical jump when assessing patients with an ACL injury, as this could help identify asymmetries, and potentially improve treatment, criteria used to clear athletes to sport, and re-injury prevention.
DEVELOPMENT OF AN ANATOMICAL SIMULATION ON HUMAN CADAVERIC HIP JOINTS
Authors: Jimenez-Cruz D. , Dubey M. , Board T. , Williams S. 
Published: July 2023

Hip joint biomechanics can be altered by abnormal morphology of the acetabulum and/or femur. This may affect load distribution and contact stresses on the articular surfaces, hence, leading to damage and degradation of the tissue. Experimental hip joint simulators have been used to assess tribology of total hip replacements and recently methods further developed to assess the natural hip joint mechanics. The aim of this study was to evaluate articular surfaces of human cadaveric joints following prolonged experimental simulation under a standard gait cycle.Four cadaveric male right hips (mean age = 62 years) were dissected, the joint disarticulated and capsule removed. The acetabulum and femoral head were mounted in an anatomical hip simulator (Simulation Solutions, UK). A simplified twin peak gait cycle (peak load of 3kN) was applied. Hips were submerged in Ringers solution (0.04% sodium azide) and testing conducted at 1 Hertz for 32 hours (115,200 cycles). Soft tissue degradation was recorded using photogrammetry at intervals throughout testing.All four hips were successfully tested. Prior to simulation, two samples exhibited articular surface degradation and one had a minor scalpel cut and a small area of cartilage delamination. The pre-simulation damage got slightly worse as the simulation continued but no new areas of damage were detected upon inspection. The samples without surface degradation, showed no damage during testing and the labral sealing effect was more obvious in these samples.The fact that no new areas of damage were detected after long simulations, indicates that the loading conditions and positioning of the sample were appropriate, so the simulation can be used as a control to compare mechanical degradation of the natural hip when provoked abnormal conditions or labral tissue repairs are simulated.
ROUTINE SURGICAL ANTISEPTIC AGENTS ARE INEFFECTIVE IN THE ERADICATION OF TYPICAL PJI BIOFILM FORMED ON ORTHOPAEDIC IMPLANT MATERIAL IN VITRO AND THE ABSENCE OF AN ANTISEPTIC NEUTRALIZATION STAGE GIVES THE FALSE IMPRESSION OF EFFICACY
Authors: Davidson D. , Spratt D. , Liddle A. 
Published: July 2023

Prosthetic joint infection (PJI) is a serious complication following joint replacement. Antiseptic solutions are often used for intraoperative wound irrigation particularly in cases of revision for PJI. Antiseptic irrigation is intended to eradicate residual bacteria which may be either free floating or in residual biofilm although there is no clear clinical efficacy for its use. Also, reviewing the scientific literature there is discordance in in vitro results where some studies questions antiseptic efficacy whilst others suggest that even at low concentration antiseptic agents are effective at eradicating bacterial biofilms.The aim of this in vitro study was to establish the efficacy of undiluted antiseptic agents at eradication of a typical PJI forming biofilm and determine the importance of an antiseptic neutralisation step in this assessment.Mature Staphylococcus epidermidis biofilms grown on TiAl6V4 discs were submerged in chlorohexidine (CHL) gluconate 4%, povidone-iodine (PI) 10% or phosphate-buffered saline (PBS) control solution. The discs were then rinsed, the biofilm bacteria suspended in solution using sonication and vortexing, and the viable count (CFU/ml) of the bacterial suspensions determined. The rinse/suspension solution was either (a) PBS or (b) Dey-Engley neutralization broth (NB).When PBS was used to rinse/suspend the biofilm a highly significant, 7.5 and 4.1, mean log reduction in biofilm vitality was observed from the control, for CHL 4% and PI 10%, respectively. However, when NB was the rinse/suspension solution the apparent antiseptic biofilm eradication efficacy was replaced with a statistically significant but clinically irrelevant less the one log-reduction in biofilm vitality.Clinical antiseptic agents are ineffective at eradicating S. epidermidis biofilm in an in vitro PJI model and absence of a neutralisation step gives the false impression of efficacy. Antiseptics alone are an ineffective treatment for biofilm related PJI and no substitute for meticulous debridement.