In absence of available quantitative measures, the assessment of fracture healing based on clinical examination and X-rays remains a subjective matter. Lacking reliable information on the state of healing, rehabilitation is hardly individualized and mostly follows non evidence-based protocols building on common guidelines and personal experience. Measurement of fracture stiffness has been demonstrated as a valid outcome measure for the maturity of the repair tissue but so far has not found its way to clinical application outside the research space. However, with the recent technological advancements and trends towards digital health care, this seems about to change with new generations of instrumented implants – often unfortunately termed “smart implants” – being developed as medical devices. The
Introduction. To develop an international guideline (AOGO) about use of osteobiologics in Anterior Cervical Discectomy and Fusion (ACDF) for treating degenerative spine conditions. Method. The guideline development process was guided by
INTRODUCTION. Intramedullary nail fixation has been used for successful treatment of long bone fracture such as humerus, tibia and femur. We look at the experience of our trauma unit in treating long bone fracture using the
Open reduction and internal fixation using plate osteosynthesis for midshaft clavicle fractures is often associated with hardware prominance. Although clinical studies have suggested a role for the use of thinner 2.7mm plates as a means of increasing cosmetic acceptability this still remains an area of controversy. We investigated the effect of plate size (2.7mm vs. 3.5mm), plate treatment (annealed vs. cold worked) and number of screws on the stiffness and yield point. Twenty-four synthetic clavicles were randomly divided into four treatment groups - Synthes (Synthes, Paoli, PA) 2.7mm cold-worked calcaneal reconstruction plate with six or eight bicortical screws; 3.5mm LCP reconstruction plate (RP) and 3.5mm LCP pre-contoured superior-anterior clavicle plate (PCSA). After measuring the baseline stiffness of the intact specimens, all clavicles were plated, a wedge-shaped inferior defect was created and testing performed using a cantilever-bending model. Statistical analysis was performed using one-way ANOVA with Tukey's multiple comparison test with significance set at a P value <0.05.Background
Methods
With an aging population and increase in total knee arthroplasty, periprosthetic distal femur fractures (PDFFs) have increased. The differences between these fractures and native distal femur fractures (NDFF) have not been comprehensively investigated. The purpose of this study was to compare the demographic, fracture, and treatment details of PDFFs compared to NDFFs. A retrospective study of patients ≥ 18 years old who underwent surgical treatment for either a NDFF or a PDFF from 2010 to 2020 at a level 1 trauma center was performed. Demographics,
Osteoclasts (OCs) are multinucleated cells that play a pivotal role in skeletal development and bone remodeling. Abnormal activation of OCs contributes to the development of bone-related diseases, such as osteoporosis, bone metastasis and osteoarthritis. Restoring the normal function of OCs is crucial for bone homeostasis. Recently, RNA therapeutics emerged as a new field of research for osteoarticular diseases. The aim of this study is to use non-coding RNAs (ncRNAs) to molecularly engineer OCs and modulate their function. Specifically, we investigated the role of the microRNAs (namely miR-16) and long ncRNAs (namely DLEU1) in OCs differentiation and fusion. DLEU1/DLEU2 region, located at chromosome 13q14, also encodes miR-15 and miR-16. Our results show that levels of these ncRNA transcripts are differently expressed at distinct stages of the OCs differentiation. Specifically, silencing of DLEU1 by small interfering RNAs (siDLEU1) and overexpression of miR-16 by synthetic miRNA mimics (miR-16-mimics) led to a significant reduction in the number of OCs formed per field (OC/field), both at day 5 and 9 of the differentiation stage. Importantly, time-lapse analysis, used to track OCs behavior, revealed a significant decrease in fusion events after transfection with siDLEU1 or miR-16-mimics and an alteration in the fusion mode and partners. Next, we investigated the migration profile of these OCs, and the results show that only miR-16-mimics-OCs, but not siDLEU-OCs, have a lower percentage of immobile cells and an increase in cells with mobile regime, compared with controls. No differences in cell shape were found. Moreover, mass-spectrometry quantitative proteomic analysis revealed independent effects of siDLEU1 and miR-16-mimics at the protein levels. Importantly, DLEU1 and miR-16 act by distinct processes and pathways. Collectively, our findings support the ncRNAs DLEU1 and miR-16 as therapeutic targets to modulate early stages of OCs differentiation and, consequently, to impair OC fusion, advancing ncRNA-therapeutics for bone-related diseases. Acknowledgements: Authors would like to thank to
Introduction. Intervertebral disc degeneration has been associated with low back pain (LBP) which is a major cause of long-term disability worldwide. Observed mechanical and biological modifications have been related to decreased water content. Clinical traction protocols as part of LBP management have shown positive outcomes. However, the underlying mechanical and biological processes are still unknown. The study purpose was to evaluate the impact of unloading through traction on the mechanobiology of healthy bovine tail discs in culture. Method. We loaded bovine tail discs (n=3/group) 2h/day at 0.2Hz for 3 days, either in dynamic compression (-0.01MPa to -0.2MPa) or in dynamic traction (-0.01MPa to 0.024MPa). In between the dynamic loading sessions, we subjected the discs to static compression loading (-0.048MPa). We assessed biomechanical and biological parameters. Result. Over the 3 days of loading, disc height decreased upon dynamic compression loading but increased upon unloading. The neutral zone was restored for all samples at the end of the dynamic unloading. Upon dynamic compression, the stiffness increased over time while the hysteresis decreased. Upon dynamic unloading, sulfated glycosaminoglycan (sGAG) release in the medium was lower at the endpoint. In the outer annulus fibrosus (AFo), we saw a higher water/sGAG of at least 30%. In the nucleus pulposus, COL2 mRNA was expressed more highly upon dynamic unloading while MMP3, iNOS and TRPV4 expression levels were lower. In the AFo of the unloading group, COL2 expression was higher but COL1 was lower. Conclusion. The biomechanical and biological results consistently indicate that dynamic unloading of healthy bovine discs in culture facilitates water uptake and promotes an anti-catabolic response which reflects a function optimization of the disc. This work combines biomechanical and biological results and opens the door to evidence-based improvement of regenerative protocols for degenerated discs and conservative LBP management. This study is funded by
Biomaterials with mechanical or biological competence are ubiquitous in musculoskeletal disorders, and understanding the inflammatory response they trigger is key to guide tissue regeneration. While macrophage role has been widely investigated, immune response is regulated by other immune cells, including neutrophils, the most abundant leukocyte in human blood. As first responders to injury, infection or material implantation, neutrophils recruit other immune cells, and therefore influence the onset and resolution of chronic inflammation, and macrophage polarization. This response depends on the physical and chemical properties of the biomaterials, among other factors. In this study we report an in vitro culture model to describe the most important neutrophil functions in relation to tissue repair. We identified neutrophil survival and death, neutrophils extracellular trap formation, release of reactive oxygen species and degranulation with cytokines release as key functions and introduced a corresponding array of assays. These tests were suitable to identify clear differences in the response by neutrophils that were cultured on material of different origin, stiffness and chemical composition. Overall, substrates from biopolymers of natural origin resulted in increased survival, less neutrophil extracellular trap formation, and more reactive oxygen species production than synthetic polymers. Within the range of mechanical properties explored (storage modulus below 5 k Pa), storage modulus of covalently crosslinked hyaluronic acid hydrogels did not significantly alter neutrophils response, whereas polyvinyl alcohol gels of matching mechanical properties displayed a response indicating increased activation. Additionally, we present the effect of material stiffness, charge, coating and culture conditions in the measured neutrophils response. Further studies are needed to correlate the neutrophil response to tissue healing. By deciphering how neutrophils initiate and modulate the immune response to material implantation, we aim at introducing new principles to design immunomodulatory biomaterials for musculoskeletal disorders. Acknowledgments. This work was supported by the
Treatment of both simple and complex patella fractures is a challenging clinical problem. The aim of this study was to investigate the biomechanical performance of recently developed lateral rim variable angle locking plates versus tension band wiring used for fixation of simple and complex patella fractures. Twelve pairs of human anatomical knees were used to simulate either two-part transverse simple
The effects of dexamethasone (dex), during in vitro human osteogenesis, are contrasting. Indeed, dex downregulates SOX9 during osteogenic differentiation of human bone marrow mesenchymal stromal cells (HBMSCs). However, dex also promotes PPARG expression, resulting in the formation of adipocyte-like cells within the osteogenic monolayers. The regulation of both SOX9 and PPARG seems to be downstream the transactivation activity of the glucocorticoid receptor (GR), thus the effect of dex on SOX9 downregulation is indirect. This study aims at determining whether PPAR-γ regulates SOX9 expression levels, as suggested by several studies. HBMSCs were isolated from bone marrow of patients with written informed consent. HBMSCs were cultured in different osteogenic induction media containing 10 or 100 nM dex. Undifferentiated cells were used as controls. Cells were treated either with a pharmacological PPAR-γ inhibitor T0070907 (donors n=4) or with a PPARG-targeting siRNA (donors n=2). Differentiation markers or PPAR-γ target genes were analysed by RT-qPCR. Mineral deposition was assessed by ARS staining. Two-way ANOVA followed by a Tukey's multiple comparison test compared the effects of treatments. At day 7, T0070907 downregulated ADIPOQ and upregulated CXCL8, respectively targets of PPAR-γ-mediated transactivation and transrepression. RUNX2 and SOX9 were also significantly downregulated in absence of dex. PPARG was successfully downregulated by siRNA. ADIPOQ expression was also inhibited, while CXCL8 did not show any significant difference between siRNA treatment groups. RUNX2 was downregulated by the PPARG-siRNA treatment in presence of 100 nM dexamethasone, while SOX9 levels were not affected. ARS showed no change in the mineralization levels when PPARG expression or activity was inhibited. Understanding how dex regulates HBMSC differentiation is of pivotal importance to refine current in vitro models. These results suggest that PPARG does not mediate SOX9 downregulation. Unexpectedly, RUNX2 expression was also unaltered or even downregulated after PPAR-γ inhibition. Acknowledgements:
Treatment of simple and complex patella fractures represents a challenging clinical problem. Controversy exists regarding the most appropriate fixation method. Tension band wiring, aiming to convert the pulling forces on the anterior aspect of the patella into compression forces across the fracture site, is the standard of care, however, it is associated with high complication rates. Recently, anterior variable-angle locking plates have been developed for treatment of simple and comminuted patella fractures. The aim of this study was to investigate the biomechanical performance of the novel anterior variable-angle locking plates versus tension band wiring used for fixation of simple and complex patella fractures. Sixteen pairs of human cadaveric knees were used to simulate either two-part transverse simple
Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery.
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
Introduction. Tibiocalcaneal arthrodesis with a retrograde intramedullary nail is an established procedure considered as a salvage in case of severe arthritis and deformity of the ankle and subtalar joints [1]. Recently, a significant development in hindfoot arthrodesis with plates has been indicated. Therefore, the aim of this study was to compare a plate specifically developed for arthrodesis of the hindfoot with an already established nail system [2]. Method. Sixteen paired human cadaveric lower legs with removed forefoot and cut at mid-tibia were assigned to two groups for tibiocalcaneal arthrodesis using either a hindfoot arthrodesis nail or an arthrodesis plate. The specimens were tested under progressively increasing cyclic loading in dorsiflexion and plantar flexion to failure, with monitoring via motion tracking. Initial stiffness was calculated together with range of motion in dorsiflexion and plantar flexion after 200, 400, 600, 800, and 1000 cycles. Cycles to failure were evaluated based on 5° dorsiflexion failure criterion. Result. Initial stiffness in dorsiflexion, plantar flexion, varus, valgus, internal rotation and external rotation did not differ significantly between the two arthrodesis techniques (p ≥ 0.118). Range of motion in dorsiflexion and plantar flexion increased significantly between 200 and 1000 cycles (p < 0.001) and remained not significantly different between the groups (p ≥ 0.120). Cycles to failure did not differ significantly between the two techniques (p = 0.764). Conclusion. From biomechanical point of view, both tested techniques for tibiocalcaneal arthrodesis appear to be applicable. However, clinical trials and other factors, such as extent of the deformity, choice of the approach and preference of the surgeon play the main role for implant choice. Acknowledgements. This study was performed with the assistance of the
The lateral wall thickness (LWT) in trochanteric femoral fractures is a known predictive factor for postoperative fracture stability. Currently, the
Freehand distal interlocking of intramedullary nails remains a challenging task. If not performed correctly it can be a time consuming and radiation expensive procedure. Recently, the
Introduction. Transosseous flexion-distraction injuries of the spine typically require surgical intervention by stabilizing the fractured vertebra during healing with a pedicle-screw-rod constructs. As healing is taking place the load shifts from the implant back to the spine. Monitoring the load-induced deflection of the rods over time would allow quantifiable postoperative assessment of healing progress without the need for radiation exposure or frequent hospital visits. This approach, previously demonstrated to be effective in assessing fracture healing in long bones and monitoring posterolateral spinal fusion in sheep, is now being investigated for its potential in evaluating lumbar vertebra transosseous fracture healing. Method. Six human cadaveric spines were instrumented with pedicle-screws and rods spanning L3 vertebra. The spine was loaded in Flexion-Extension (FE), Lateral-Bending (LB) and Axial-Rotation (AR) with an intact L3 vertebra (representing a healed vertebra) and after transosseous disruption, creating an
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/
Introduction. With advances in artificial intelligence, the use of computer-aided detection and diagnosis in clinical imaging is gaining traction. Typically, very large datasets are required to train machine-learning models, potentially limiting use of this technology when only small datasets are available. This study investigated whether pretraining of fracture detection models on large, existing datasets could improve the performance of the model when locating and classifying wrist fractures in a small X-ray image dataset. This concept is termed “transfer learning”. Method. Firstly, three detection models, namely, the faster region-based convolutional neural network (faster R-CNN), you only look once version eight (YOLOv8), and RetinaNet, were pretrained using the large, freely available dataset, common objects in context (COCO) (330000 images). Secondly, these models were pretrained using an open-source wrist X-ray dataset called “Graz Paediatric Wrist Digital X-rays” (GRAZPEDWRI-DX) on a (1) fracture detection dataset (20327 images) and (2) fracture location and classification dataset (14390 images). An orthopaedic surgeon classified the small available dataset of 776 distal radius X-rays (Arbeidsgmeischaft für Osteosynthesefragen Foundation / Orthopaedic Trauma Association;