bluuebunny/crossref_metadata_2025_split huggingface dataset:
CO-CULTURE OF MESENCHYMAL STROMAL CELLS AND LIGAMENTOCYTES ON TRIPHASIC EMBROIDERED SCAFFOLDS FOR ANTERIOR CRUCIATE LIGAMENT ENTHESIS TISSUE ENGINEERING
Authors: Gögele C. , Vogt J. , Hahn J. , Breier A. , Schröpfer M. , Meyer M. , Schäfer-Eckart K. , Schulze-Tanzil G. 
Published: July 2023

Successful anterior cruciate ligament (ACL) reconstructions strive a firm ligament-bone integration. Therefore, the aim of this study was to address in more detail the enthesis as the thriphasic bone attachment of the ACL using a tissue engineering approach. To establish a tissue-engineered enthesis-like construct, triphasic scaffolds embroidered from poly(L-lactide-co-caprolactone) and polylactic acid functionalized with collagen foam were colonized with osteogenically differentiated human mesenchymal stromal cells (hMSCs) and lapine (L) ACL fibroblasts.These triphasic scaffolds with a bone-, a fibrocartilage transition- and a ligament phase were seeded directly after spheroid assembly or with 14 days precultured LACL fibroblast spheroids and 14 days osteogenically differentiated hMSCs spheroids (=longer preculture) and cultured for further 14 days. Cell survival was tested. Collagen type I and vimentin were immunolabeled and the content of DNA and sulfated glycosaminoglycan (sGAG) was quantified. The relative gene expression of tenascin C, type I and X collagens, Mohawk and Runx2 was analyzed.Compared to the LACL spheroids the hMSC spheroids adhered better to the scaffold surface with faster cell outgrowth on the fibers. Collagen type I and vimentin were mainly detected in the hMSCs colonizing the bone zone. The DNA content was generally higher in the bone (hMSCs) than in the ligament zones and after short spheroid preculture higher than after longer preculture whereas the sGAG content was greater after longer preculture for both cell types. The longer precultivated hMSCs expressed more type I collagen in comparison to those only shortly precultured before scaffold seeding. Type I collagen and tenascin C were higher expressed in scaffolds directly colonized with LACL compared to those seeded after longer spheroid preculture. The gene expression of ECM components and transcription factors depended on cell type and preculturing condition.Zonal colonization of triphasic scaffolds using the spheroid method is possible offering a novel approach for enthesis tissue engineering.
IS POOLING OF DATA POSSIBLE IN STUDIES EVALUATING OPEN TIBIAL SHAFT FRACTURES REQUIRING FLAP COVERAGE?
Authors: Makaram N. , Al-Hourani K. , Nightingale J. , Ollivere B. , Ward J. , Tornetta III P. , Duckworth A. 
Published: July 2023

The aim of this study was to perform a systematic review of the literature on Gustilo-Anderson (GA) type IIIB open tibial shaft (AO-42) injuries to determine the consistency of reporting in the literature.A search of PubMed, EMBASE and Cochrane Central Register of Controlled Trials was performed to identify relevant studies published from January 2000 to January 2021 using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The study was registered using the PROSPERO International prospective register of systematic reviews. Patient/injury demographics, management and outcome reporting were recorded.There were 32 studies that met the inclusion criteria with a total of 1,947 patients (70.3% male, 29.7% female). There were 6 studies (18.8%) studies that reported on comorbidities and smoking, with mechanism of injury reported in 22 (68.8%). No studies reported on all operative criteria included, with only three studies (9.4%) reporting for time to antibiotics, 14 studies (43.8%) for time from injury to debridement and nine studies (28.1%) for time to definitive fixation. All studies reported on the rate of deep infection, with a high proportion documenting union rate (26/32, 81.3%). However, only two studies reported on mortality or on other post-operative complications (2/32, 6.3%). Only 12 studies (37.5%) provided any patient reported outcomes.This study has demonstrated a deficiency and a lack of standardized variable and outcome reporting in the orthopaedic literature for Gustilo-Anderson type IIIB open tibial shaft fractures. We propose a future international collaborative Delphi process is needed to standardize.
GUIDING HUMAN MUSCLE-DERIVED STEM CELL DIFFERENTIATION TOWARDS CHONDROCYTES BY HYDROGEL SCAFFOLDS RELEASING GROWTH FACTORS
Authors: Mazetyte-Godiene A. , Vailionyte A. , Valiokas R. , Usas A. 
Published: July 2023

Herein we address, hyaline cartilage regeneration issue by engineering a synthetic biocompatible hydrogel scaffold capable to promote chondrogenic differentiation. In this study, the chemically crosslinked hydrogels consisting of synthetic peptides that have the collagen-like sequence Cys-Gly-(Pro-Lys-Gly)4 (Pro-Hyp-Gly)4 (Asp-Hyp-Gly)4- conjugated with RGD sequence (CLP-RGD) and crosslinked hydrogels of type I collagen (CA) were used. For cartilage formation, we used human skeletal muscle-derived stem/progenitor cells (hMDSPCs) set for differentiation towards a chondrogenic lineage by BMP-7 and TGF-ß3 growth factors.Initially 150, 100 and 75 ng of BMP-7and TGF-ß3 growth factors were inserted in each scaffold and amount of growth factors diffusing out of the scaffolds was observed by ELISA assays. In vitro experiments were performed by seeding hMDSPCs onto hydrogels loaded with growth factors (75ng/scaffold) and cultured for 28 days. Cartilage formation was monitored by ELISA and RT-PCR assays. All experiments were performed in triplicates or quadruplicates.Growth factors incorporation strategy allowed a sustained release of TGF-ß3 growth factor, 6.00.3% of the initially loaded amount diffused out after 4 h and 2.70.5% already at the second time point (24h) from CA and CLP-RGD substrates. For the BMP-7 growth factor, 13.12.3% and 15.751.6% of the initially loaded amount diffused out after 4 h, 1.70.2% and 2.450.3% at the second time point (24 h) from CA and CLP-RGD respectively. In vitro experiments shown that scaffolds with immobilized growth factors resulted in higher collagen type II accumulation when compared to the scaffolds alone. The gene expression on CLP-RGD hydrogels with growth factors has shown lower collagen type I expression and higher aggrecan expression compared to day 0. However, we also report increased collagen X gene expression on CA hydrogels (with growth factors).Our results support the potential of the strategy of combining hydrogels functionalized with differentiation factors toward improving cartilage repair.
RETRIEVAL ANALYSIS OF DUAL MOBILITY POLYETHYLENE LINERS FOR TOTAL HIP ARTHROPLASTY
Authors: Smeeton M. , Wilcox R. , Isaac G. , Anderson J. , Board T. , Van Citters D.W. , Williams S. 
Published: July 2023

Dual mobility (DM) total hip replacements (THRs) were introduced to reduce dislocation risk, which is the most common cause of early revision. Although DM THRs have shown good overall survivorship and low dislocation rates, the mechanisms which describe how these bearings function in-vivo are not fully understood. Therefore, the study aim was to comprehensively assess retrieved DM polyethylene liners for signs of damage using visual inspection and semi-quantitative geometric assessment methods.Retrieved DM liners (n=18) were visually inspected for the presence of surface damage, whereby the internal and external surfaces were independently assigned a score of one (present) or zero (not present) for seven damage modes. The severity of damage was not assessed. The material composition of embedded debris was characterised using energy-dispersive x-ray analysis (EDX). Additionally, each liner was geometrically assessed for signs of wear/deformation [1].Scratching and pitting were the most common damage modes on either surface. Additionally, burnishing was observed on 50% of the internal surfaces and embedded debris was identified on 67% of the external surfaces. EDX analysis of the debris identified several materials including titanium, cobalt-chrome, iron, and tantalum. Geometric analysis demonstrated highly variable damage patterns across the liners.The incidence of burnishing was three times greater for the internal surfaces, suggesting that this acts as the primary articulation site. The external surfaces sustained more observable damage as evidenced by a higher incidence of embedded debris, abrasion, delamination, and deformation. In conjunction with the highly variable damage patterns observed, these results suggest that DM kinematics are complex and may be influenced by several factors (e.g., soft tissue fibrosis, patient activities) and thus further investigation is warranted.
COMPARATIVE STUDY ON THE EFFECT OF COLLAGEN AND FIBRIN HYDROGELS OF VARYING STIFFNESS ON MESENCHYMAL STEM CELL PARACRINE ACTIONS
Authors: Maestro-Paramio L. , García-Rey E. , Bensiamar F. , Rodríguez-Lorenzo L. , Vilaboa N. , Saldaña L. 
Published: July 2023

Mesenchymal stem cells (MSC) have potent immunomodulatory and regenerative effects via soluble factors. One approach to improve stem cell-based therapies is encapsulation of MSC in hydrogels based on natural proteins such as collagen and fibrin, which play critical roles in bone healing. In this work, we comparatively studied the influence of collagen and fibrin hydrogels of varying stiffness on the paracrine interactions established by MSC with macrophages and osteoblasts.Type I collagen and fibrin hydrogels in a similar stiffness range loaded with MSC from donants were prepared by modifying the protein concentration. Viability and morphology of MSC in hydrogels as well as cell migration rate from the matrices were determined. Paracrine actions of MSC in hydrogels were evaluated in co-cultures with human macrophages from healthy blood donors or with osteoblasts from bone explants of patients with osteonecrosis of the femoral head.Lower matrix stiffness resulted in higher MSC viability and migration. Cell migration rate from collagen hydrogels was higher than from fibrin matrices. The secretion of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E2 (PGE2) by MSC in both collagen and fibrin hydrogels increased with increasing matrix stiffness. Tumor necrosis factor-α (TNF-α) secretion by macrophages cultured on collagen hydrogels was lower than on fibrin matrices. Interestingly, higher collagen matrix stiffness resulted in lower secreted TNF-α while the trend was opposite on fibrin hydrogels. In all cases, TNF-α levels were lower when macrophages were cultured on hydrogels containing MSC than on empty gels, an effect partially mediated by PGE2. Finally, mineralization capacity of osteoblasts co-cultured with MSC in hydrogels increased with increasing matrix stiffness, although this effect was more notably for collagen hydrogels.Paracrine interactions established by MSC in hydrogels with macrophages and osteoblasts are regulated by matrix composition and stiffness.
CAN SMART PHONE VIDEO-BASED POSE ESTIMATION ACCURATELY CLASSIFY LOW BACK PHYSIOTHERAPY EXERCISES VIA MACHINE LEARNING?
Authors: Arrowsmith C. , Burns D. , Mak T. , Hardisty M. , Whyne C. 
Published: July 2023

Access to health care, including physiotherapy, is increasingly occurring through virtual formats. At-home adherence to physical therapy programs is often poor and few tools exist to objectively measure low back physiotherapy exercise participation without the direct supervision of a medical professional. The aim of this study was to develop and evaluate the potential for performing automatic, unsupervised video-based monitoring of at-home low back physiotherapy exercises using a single mobile phone camera.24 healthy adult subjects performed seven exercises based on the McKenzie low back physiotherapy program while being filmed with two smartphone cameras. Joint locations were automatically extracted using an open-source pose estimation framework. Engineered features were extracted from the joint location time series and used to train a support vector machine classifier (SVC). A convolutional neural network (CNN) was trained directly on the joint location time series data to classify exercises based on a recording from a single camera. The models were evaluated using a 5-fold cross validation approach, stratified by subject, with the class-balanced accuracy used as the performance metric.Optimal performance was achieved when using a total of 12 pose estimation landmarks from the upper and lower body, with the SVC model achieving a classification accuracy of 96±4% and the CNN model an accuracy of 97±2%.This study demonstrates the feasibility of using a smartphone camera and a supervised machine learning model to effectively assess at-home low back physiotherapy adherence. This approach could provide a low-cost, scalable method for tracking adherence to physical therapy exercise programs in a variety of settings.
TREATMENT AFFECTS LOAD-TO-FAILURE AND MICRODAMAGE ACCUMULATION IN HEALTHY AND OSTEOLYTIC RAT VERTEBRAE
Authors: Tolgyesi A. , Huang C. , Akens M. , Hardisty M. , Whyne C.M. 
Published: July 2023

Bone turnover and microdamage are impacted by skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. This study aimed to establish an understanding of microdamage accumulation and load to failure in healthy and osteolytic vertebrae following cancer treatment (stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX)).Forty-two 6-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo) were studied; 22 were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Animals were randomly assigned to four groups: untreated (healthy=5, osteolytic=6), SBRT on day 14 (healthy=6, osteolytic=6), ZA on day 7 (healthy=4, osteolytic=5), and DTX on day 14 (healthy=5, osteolytic=5). Animals were euthanized on day 21. L1-L3 motion segments were compression loaded to failure and force-displacement data recorded. T13 vertebrae were stained with BaSO4 and µCT imaged (90kVp, 44uA, 4.9µm) to visualize microdamage location and volume. Damage volume fraction (DV/BV) was calculated as the ratio of BaSO4 to bone volume. Differences in mean load-to-failure were compared using three-way ANOVA (disease status, treatment, cells injected). Differences in mean DV/BV between treatment groups were compared using one-way ANOVA.Treatment had a significant effect on load-to-failure (p=0.004) with ZA strengthening the healthy and osteolytic vertebrae. Reduced strength post SBRT seen in the metastatic (but not the healthy) group may be explained by greater tumor involvement secondary to higher cell injection concentrations. Untreated metastatic samples had higher DV/BV (16.25±2.54%) compared to all treatment groups (p<0.05) suggesting a benefit of treatment to bone quality.Focal and systemic cancer treatments were shown to effect load-to-failure and microdamage accumulation in healthy and osteolytic vertebrae. Developing a better understanding of how treatments effect bone quality and mechanical stability is critical for effective management of patients with spinal metastases.
SHORT VERSUS LONG INTRAMEDULLARY NAILS FOR INTERTROCHANTERIC HIP FRACTURE: META-ANALYSIS
Authors: Mariscal G. , Barrés M. , Barrios C. , Tintó M. , Baixauli F. 
Published: July 2023

To conduct a meta-analysis for intertrochanteric hip fractures comparing in terms of efficacy and safety short versus long intralomedullary nails.A pubmed search of the last 10 years for intertrochanteric fracture 31A1-31A3 according to the AO/OTA classification was performed. Baseline characteristics of each article were obtained, complication measures were analyzed: Peri-implant fracture, reoperations, deep/superficial infection, and mortality. Clinical variables consisted of blood loss (mL), length of stay (days), time of surgery (min) and nº of transfusions. Functional outcomes were also recorded. A meta-analysis was performed with Review Manager 5.4.Twelve studies were included, nine were retrospective. The reoperations rate was lower in the short nail group and the peri-implant fracture rate was lower in the long nail group (OR 0.58, 95% CI 0.38 to 0.88) (OR 1.88, 95% CI 1.04 to 3.43). Surgery time and blood loss was significantly higher in the long nail group (MD −12.44, 95% CI −14.60 to −10.28) (MD −19.36, 95% CI −27.24 to −11.48). There were no differences in functional outcomes.The short intramedullary nail has a higher risk of peri-implant fracture; however, the reoperation rate is lower compared to the long nail. Blood loss and surgery time was higher in the long nail group.
TARGETING MENINGEAL LYMPHATICS AS A THERAPEUTIC STRATEGY FOR ALZHEIMER's DISEASE: A NOVEL APPLICATION OF CRANIAL BONE MANOEUVRE
Authors: LU X. , BAI S. , LIN Y. , YAN L. , LI L. , WANG M. , JIANG Z. , WANG H. , YANG B. , YANG Z. , WANG Y. , FENG L. , JIANG X. , PONOMAREV E. , LEE W. , LIN S. , KO H. , LI G. 
Published: July 2023

Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms.Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment.CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies).CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.
N-TELOPEPTIDE DERIVED FROM TYPE II COLLAGEN UPREGULATES EXPRESSION OF BETA1 INTEGRIN AND MMPS IN CARTILAGE OF PATIENTS RECEIVING HIP OR KNEE ARTHROPLASTY
Authors: Mao J. , Ding Y. , Huang L. , Wang Q. , Ding L. 
Published: July 2023

Previous studies showed that telo-peptides degraded from type II collagen, a type of collagen fragments, could induce cartilage damage in bovine stifle joints. We aim to investigate the role of integrins (ITGs) and matrix metalloproteinases (MMPs) in collagen fragment-induced human cartilage damage that is usually observed in osteoarthritis (OA). We hypothesized that N-telopeptide (NT) derived from type II collagen could up-regulate the expression of β1 integrin (ITGB1) and then MMPs that may lead to osteoarthritic cartilage damage.Human chondrocytes were isolated from femoral head or tibial plateau of patients receiving arthroplasty (N = 24). Primary chondrocyte cultures were either treated with 30 µM NT, or 30 µM scrambled NT (SN), or PBS, or left untreated for 24 hrs. Total proteins and RNAs were extracted for examination of expression of ITGB1 and MMPs-3&13 with Western blotting and quantitative real-time PCR.Compared to untreated or PBS treated chondrocytes, NT-treated chondrocytes expressed significantly higher levels of ITGB1 and MMPs-3&-13. However, SN also up-regulated expression of ITGB1 and MMP-13.ITGB1 and MMPs-3&-13 might mediate the catalytic effect of NT, a type of collagen fragments, on human cartilage damage that is a hallmark of OA.
INFLUENCE OF ANTIBACTERIAL IMPLANT COATINGS ON THE VIABILITY OF GRAM-POSITIVE AND GRAM-NEGATIVE BACTERIA AND THE IN VITRO MINERALIZATION
Authors: Wulfhorst M. , Büssemaker H. , Meinshausen A-K. , Herbster M. , Döring J. , Mai V. , Lohmann C. , Kautz A. , Laube T. , Wyrwa R. , Schnabelrauch M. , Bertrand J. 
Published: July 2023

The implantation of endoprosthesis is a routine procedure in orthopaedics. Endoprosthesis are mainly manufactured from ceramics, polymers, metals or metal alloys. To ensure longevity of the implants they should be as biocompatible as possible and ideally have antibacterial properties, to avoid periprosthetic joint infections (PJI). Various antibacterial implant materials have been proposed, but have so far only been used sporadically in patients. PJI is one of the main risk factors for revision surgeries. The aim of the study was to identify novel implant coatings that both exhibit antibacterial properties whilst having optimal biocompatibility.Six different novel implant coatings and surface modifications (EBM TiAl6V4, strontium, TiCuN, TiNbN, gentamicin phosphate (GP), gentamicin phosphate+cationic polymer (GP+CP)) were compared to standard CoCrMo-alloy. The coatings were further characterized with regard to the surface roughness. E. coli and S. capitis were cultured on the modified surfaces to investigate the antibacterial properties. To quantify bacterial proliferation the optical density (OD) was measured and viability was determined using colony forming units (CFU). Murine bone marrow derived macrophages (BMMs) were cultured on the surfaces and differentiated into osteoblasts to quantify the mineralisation using the alizarin red assay.All novel coatings showed reduced bacterial proliferation and viability compared to standard CoCrMo-alloy. A significant reduction was observed for GP and GP+CP coated samples compared to CoCrMo (ODGP,E.coli = 0.18±0.4; ODGP+CP,E.coli = 0.13±0.3; p≤0.0002; N≥7-8). An increase in osteoblast-mediated mineralisation was observed on all surfaces tested compared to CoCrMo. Furthermore, GP and GP+CP coated samples showed a statistically significant increase (MGP = 0.21±0.1; MGP+CP = 0.25±0.2; p<0.0001; N≥3-6).The preliminary data indicates that the gentamicin containing surfaces have the most effective antibacterial property and the highest osseointegrative capacity. The use of antibiotic coatings on prostheses could reduce the risk of PJI while being applied on osseointegrative implant surfaces.