RESUMEN
Beyond the critical role of cell nuclei in gene expression and DNA replication, they also have a significant influence on cell mechanosensation and migration. Nuclear stiffness can impact force transmission and, furthermore, act as a physical barrier to translocation across tight spaces. As such, it is of wide interest to accurately characterize nucleus mechanical behavior. In this study, we present a computational investigation of the in situ deformation of a heterogeneous chondrocyte nucleus. A methodology is developed to accurately reconstruct a three-dimensional finite-element model of a cell nucleus from confocal microscopy. By incorporating the reconstructed nucleus into a chondrocyte model embedded in pericellular and extracellular matrix, we explore the relationship between spatially heterogeneous nuclear DNA content, shear stiffness, and resultant shear strain. We simulate an externally applied extracellular matrix shear deformation and compute intranuclear strain distributions, which are directly compared with corresponding experimentally measured distributions. Simulations suggest that the mechanical behavior of the nucleus is highly heterogeneous, with a nonlinear relationship between experimentally measured grayscale values and corresponding local shear moduli (µn). Three distinct phases are identified within the nucleus: a low-stiffness mRNA-rich interchromatin phase (0.17 kPa ≤ µn ≤ 0.63 kPa), an intermediate-stiffness euchromatin phase (1.48 kPa ≤ µn ≤ 2.7 kPa), and a high-stiffness heterochromatin phase (3.58 kPa ≤ µn ≤ 4.0 kPa). Our simulations also indicate that disruption of the nuclear envelope associated with lamin A/C depletion significantly increases nuclear strain in regions of low DNA concentration. We further investigate a phenotypic shift of chondrocytes to fibroblast-like cells, a signature for osteoarthritic cartilage, by increasing the contractility of the actin cytoskeleton to a level associated with fibroblasts. Peak nucleus strains increase by 35% compared to control, with the nucleus becoming more ellipsoidal. Our findings may have broad implications for current understanding of how local DNA concentrations and associated strain amplification can impact cell mechanotransduction and drive cell behavior in development, migration, and tumorigenesis.
Asunto(s)
Cromatina , Mecanotransducción Celular , Núcleo Celular , Condrocitos , Estrés MecánicoRESUMEN
AIM: To systematically review the qualitative literature on neurogenic bladder management to better understand the relevant psychosocial issues. METHODS: We used two reviewers to systematically review EMBASE, CINAHL, and PsycINFO for qualitative studies that included a neurogenic bladder patient population and were relevant to bladder management. We used a meta-ethnography technique to summarize and synthesize the data. RESULTS: We found 13 studies that were relevant. When choosing a bladder management technique (three studies), there were two major themes (bladder management decision makers, and characteristics and risks) that impacted the process. For studies evaluating life with a urinary catheter (five about intermittent catheters, and five about indwelling catheters), relevant themes could be arranged into three consecutive periods: First, a changed life (the initial stage of selecting and using a catheter: coping, teaching and technical challenges, and control and independence). Second, learning to live with a catheter (the practical skill and knowledge that goes into using a catheter: knowledge, adjustments, and normalization). Third, a new life (the acceptance and integration of a catheter into a person's life: problems and benefits, unpredictability, travel and social activities, intimacy and relationships, and dealing with negative emotions). Themes were generally consistent across studies. Conclusions Several important themes were identified from the existing qualitative literature; these can provide insight into how neurogenic bladder patients select a bladder management method, and how physicians can optimize their counseling and the long-term management of these patients.
Asunto(s)
Catéteres de Permanencia , Manejo de la Enfermedad , Vejiga Urinaria Neurogénica/terapia , Catéteres Urinarios , Toma de Decisiones , Humanos , Investigación CualitativaRESUMEN
While the anisotropic behavior of the complex composite myocardial tissue has been well characterized in recent years, the compressibility of the tissue has not been rigorously investigated to date. In the first part of this study, we present experimental evidence that passive-excised porcine myocardium exhibits volume change. Under tensile loading of a cylindrical specimen, a volume change of 4.1±1.95% is observed at a peak stretch of 1.3. Confined compression experiments also demonstrate significant volume change in the tissue (loading applied up to a volumetric strain of 10%). In order to simulate the multiaxial passive behavior of the myocardium, a nonlinear volumetric hyperelastic component is combined with the well-established Holzapfel-Ogden anisotropic hyperelastic component for myocardium fibers. This framework is shown to describe the experimentally observed behavior of porcine and human tissues under shear and biaxial loading conditions. In the second part of the study, a representative volumetric element (RVE) of myocardium tissue is constructed to parse the contribution of the tissue vasculature to observed volume change under confined compression loading. Simulations of the myocardium microstructure suggest that the vasculature cannot fully account for the experimentally measured volume change. Additionally, the RVE is subjected to six modes of shear loading to investigate the influence of microscale fiber alignment and dispersion on tissue-scale mechanical behavior.
Asunto(s)
Fuerza Compresiva , Ventrículos Cardíacos/citología , Miocardio/citología , Animales , Anisotropía , Fenómenos Biomecánicos , Análisis de Elementos Finitos , PorcinosAsunto(s)
Equipo Dental de Alta Velocidad/efectos adversos , Enfermedades Mandibulares/diagnóstico por imagen , Enfermedades Mandibulares/etiología , Enfisema Subcutáneo/diagnóstico por imagen , Enfisema Subcutáneo/etiología , Extracción Dental/efectos adversos , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Mandibulares/patología , Radiografía Panorámica , Enfisema Subcutáneo/patología , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
As a first line option in the treatment of acute ischemic stroke (AIS), direct aspiration is a fast and effective technique with promising outcomes. In silico models are widely used for design and preclinical assessment of new developed devices and therapeutic methods. Accurate modelling of the mechanical behaviour of blood clot is a key factor in the design and simulation of aspiration devices. In this study we develop a new constitutive model which incorporates the unrecoverable plastic deformation of clots. The model is developed based on the deformation-induced microstructural changes in fibrin network, including the formation and dissociation of the cross-links between fibrin fibres. The model is calibrated using previously reported experimentally measured permanent clot deformation following uniaxial stretching. The calibrated plasticity model is then used to simulate aspiration thrombectomy. Results reveal that inclusion of permanent plastic deformation results in â¼ 15 % increase in clot aspiration length at an applied aspiration pressure of 100 mmHg. The constitutive law developed in this study provides a basis for improved design and evaluation of novel aspiration catheters leading to increased first-pass revascularization rate.
Asunto(s)
Accidente Cerebrovascular Isquémico/cirugía , Trombosis , Simulación por Computador , Fibrina , Humanos , Trombectomía , Resultado del TratamientoRESUMEN
Cyclic strain avoidance, the phenomenon of cell and cytoskeleton alignment perpendicular to the direction of cyclic strain of the underlying 2D substrate, is an important characteristic of the adherent cell organization. This alignment has typically been attributed to the stress-fiber reorganization although observations clearly show that stress-fiber reorganization under cyclic loading is closely coupled to cell morphology and reorientation of the cells. Here, we develop a statistical mechanics framework that couples the cytoskeletal stress-fiber organization with cell morphology under imposed cyclic straining and make quantitative comparisons with observations. The framework accurately predicts that cyclic strain avoidance stems primarily from cell reorientation away from the cyclic straining rather than cytoskeletal reorganization within the cell. The reorientation of the cell is a consequence of the cell lowering its free energy by largely avoiding the imposed cyclic straining. Furthermore, we investigate the kinetics of the cyclic strain avoidance mechanism and demonstrate that it emerges primarily due to the rigid body rotation of the cell rather than via a trajectory involving cell straining. Our results provide clear physical insights into the coupled dynamics of cell morphology and stress-fibers, which ultimately leads to cellular organization in cyclically strained tissues.
RESUMEN
Mechanical thrombectomy (MT) treatment of acute ischemic stroke (AIS) patients typically involves use of stent retrievers or aspiration catheters alone or in combination. For in silico trials of AIS patients, it is crucial to incorporate the possibility of thrombus fragmentation during the intervention. This study focuses on two aspects of the thrombectomy simulation: i) Thrombus fragmentation on the basis of a failure model calibrated with experimental tests on clot analogs; ii) the combined stent-retriever and aspiration catheter MT procedure is modeled by adding both the proximal balloon guide catheter and the distal access catheter. The adopted failure criterion is based on maximum principal stress threshold value. If elements of the thrombus exceed this criterion during the retrieval simulation, then they are deleted from the calculation. Comparison with in-vitro tests indicates that the simulation correctly reproduces the procedures predicting thrombus fragmentation in the case of red blood cells rich thrombi, whereas non-fragmentation is predicted for fibrin-rich thrombi. Modeling of balloon guide catheter prevents clot fragments' embolization to further distal territories during MT procedure.
Asunto(s)
Accidente Cerebrovascular Isquémico , Trombosis , Fibrina , Humanos , Stents , Trombectomía/efectos adversos , Trombectomía/métodos , Trombosis/terapia , Resultado del TratamientoRESUMEN
Development of in-silico models of patient-specific cerebral artery networks presents several significant technical challenges: (i) The resolution and smoothness of medical CT images are much lower than the required element/cell length for FEA/CFD/FSI models; (ii) contact between vessels, and indeed self contact of high tortuosity vessel segments are not clearly identifiable from medical CT images. Commercial model construction software does not provide customised solutions for such technical challenges, with the result that accurate, efficient and automated development of patient-specific models of the cerebral vessels is not facilitated. This paper presents the development of a customised and highly automated platform for the generation of high resolution patient-specific FEA/CFD/FSI models from clinical images. This platform is used to perform the first fluid-structure-interaction patient-specific analysis of blood flow and artery deformation of an occluded cerebral vessel. Results demonstrate that in addition to flow disruption, clot occlusion significantly alters the geometry and strain distribution in the vessel network, with the blocked M2 segment undergoing axial elongation. The new computational approach presented in this study can be further developed as a clinical diagnostic tool and as a platform for thrombectomy device design.
Asunto(s)
Arterias , Trombectomía , Arterias/fisiología , Simulación por Computador , Hemodinámica , Humanos , Modelos Cardiovasculares , Programas InformáticosRESUMEN
The current study presents the development and implementation of a bespoke experimental technique to generate and characterise mode II crack initiation and propagation in arterial tissue. The current study begins with a demonstration that lap-shear testing of arterial tissue results in mixed mode fracture, rather than mode II. We perform a detailed computational design of a bespoke experimental method (which we refer to as a shear fracture ring test (SFRT)) to robustly and repeatably generate mode II crack initiation and propagation in arteries. This method is based on generating a localised region of high shear adjacent to a cylindrical loading bar. Placement of a radial notch in this region of high shear stress is predicted to result in a kinking of the crack during a mode II initiation and propagation of the crack over a long distance in the circumferential (c)-direction along the circumferential-axial (c-a) plane. Fabrication and experimental implementation of the SFRT on excised ovine aorta specimens confirms that the bespoke test method results in pure mode II initiation and propagation. We demonstrate that the mode II fracture strength along the c-a plane is eight times higher than the corresponding mode I strength determined from a standard peel test. We also calibrate the mode II fracture energy based on our measurement of crack propagation rates. The mechanisms of fracture uncovered in the current study, along with our quantification of mode II fracture properties have significant implications for current understanding of the biomechanical conditions underlying aortic dissection.
Asunto(s)
Disección Aórtica , Fracturas Óseas , Animales , Arterias , Disección , Ovinos , Estrés MecánicoRESUMEN
Cardiac hypertrophy is an adaption of the heart to a change in cardiovascular loading conditions. The current understanding is that progression may be stress or strain driven, but the multi-scale nature of the cellular remodelling processes have yet to be uncovered. In this study, we develop a model of the contractile left ventricle, with the active cell tension described by a thermodynamically motivated cross-bridge cycling model. Simulation of the transient recruitment of myosin results in correct patterns of ventricular pressure predicted over a cardiac cycle. We investigate how changes in tissue loading and associated deviations in transient force generation can drive restructuring of cellular myofibrils in the heart wall. Our thermodynamic framework predicts in-series sarcomere addition (eccentric remodelling) in response to volume overload, and sarcomere addition in parallel (concentric remodelling) in response to valve and signalling disfunction. This framework provides a significant advance in the current understanding of the fundamental sub-sarcomere level biomechanisms underlying cardiac remodelling. Simulations reveal that pathological tissue loading conditions can significantly alter actin-myosin cross-bridge cycling over the course of the cardiac cycle. The resultant variation in sarcomere stress pushes an imbalance between the internal free energy of the myofibril and that of unbound contractile proteins, initiating remodelling. The link between cross-bridge thermodynamics and myofibril remodelling proposed in this study may significantly advance current understanding of cardiac disease onset.
Asunto(s)
Ventrículos Cardíacos , Modelos Cardiovasculares , Contracción Muscular , Corazón , Miosinas , TermodinámicaRESUMEN
Thrombus fragmentation during endovascular stroke treatment, such as mechanical thrombectomy, leads to downstream emboli, resulting in poor clinical outcomes. Clinical studies suggest that fragmentation risk is dependent on clot composition. This current study presents the first experimental characterization of the composition-dependent fracture properties of blood clots, in addition to the development of a predictive model for blood clot fragmentation. A bespoke experimental test-rig and compact tension specimen fabrication has been developed to measure fracture toughness of thrombus material. Fracture tests are performed on three physiologically relevant clot compositions: a high-fibrin clot made from a 5% haematocrit (H) blood mixture, a medium-fibrin clot made form a 20% H blood mixture, a low-fibrin clot made from a 40% H blood mixture. Fracture toughness is observed to significantly increase with increasing fibrin content, i.e. red blood cell-rich clots are more prone to tear during loading compared to the fibrin-rich clots. Results also reveal that the mechanical behaviour of clot analogues is significantly different in compression and tension. Finite element cohesive zone modelling of clot fracture experiments show that fibrin fibres become highly aligned in the direction perpendicular to crack propagation, providing a significant toughening mechanism. The results presented in this study provide the first characterization of the composition-dependent fracture behaviour of blood clots and are of key importance for development of next-generation thrombectomy devices and clinical strategies. STATEMENT OF SIGNIFICANCE: This study provides a characterisation of the composition-dependent fracture toughness of blood clots. This entails the development of novel experimental techniques for fabrication and testing of blood clot compact tension fracture specimens. The study also develops cohesive zone models of fracture initiation and propagation in blood clots. Results reveal that the fracture resistance of fibrin-rich clots is significantly higher than red blood cell rich clots. Simulations also reveal that stretching and realignment of the fibrin network should be included in blood clot material models in order to accurately replicate compression-tension asymmetry and fibrin enhanced fracture toughness. The results of this study have potentially important clinical implications in terms of clot fracture risk and secondary embolization during mechanical thrombectomy procedures.
Asunto(s)
Accidente Cerebrovascular , Trombosis , Eritrocitos , Fibrina , Humanos , TrombectomíaRESUMEN
Mechanical thrombectomy can be significantly affected by the mechanical properties of the occluding thrombus. In this study, we provide the first characterisation of the volumetric behaviour of blood clots. We propose a new hyperelastic model for the volumetric and isochoric deformation of clot. We demonstrate that the proposed model provides significant improvements over established models in terms of accurate prediction of nonlinear stress-strain and volumetric behaviours of clots with low and high red blood cell compositions. We perform a rigorous investigation of the factors that govern clot occlusion of a tapered vessel. The motivation for such an analysis is twofold: (i) the role of clot composition on the in vivo occlusion location is an open clinical question that has significant implications for thrombectomy procedures; (ii) in vitro measurement of occlusion location in an engineered tapered tube can be used as a quick and simple methodology to assess the mechanical properties/compositions of clots. Simulations demonstrate that both isochoric and volumetric behaviours of clots are key determinants of clot lodgement location, in addition to clot-vessel friction. The proposed formulation is shown to provide accurate predictions of in vitro measurement of clot occlusion location in a silicone tapered vessel, in addition to accurately predicting the deformed shape of the clot.
Asunto(s)
Fibrina/química , Accidente Cerebrovascular/fisiopatología , Trombectomía/métodos , Trombosis/fisiopatología , Fuerza Compresiva , Simulación por Computador , Elasticidad , Eritrocitos , Análisis de Elementos Finitos , Fricción , Humanos , Técnicas In Vitro , Accidente Cerebrovascular Isquémico/fisiopatología , Resistencia al Corte , Silicio , Siliconas/química , Estrés Mecánico , TromboemboliaRESUMEN
Changes in acute ischemic stroke thrombi structure and composition may result in significant differences in treatment responsiveness. Ischemic stroke patients are often treated with a thrombolytic agent to dissolve thrombi, however these patients may subsequently undergo mechanical thrombectomy to remove the occlusive clot. We set out to determine if rt-PA thrombolysis treatment of blood clots changes their mechanical properties, which in turn may impact mechanical thrombectomy. Using a design-of-experiment approach, ovine clot analogues were prepared with varying composition and further exposed to different levels of compaction force to simulate the effect of arterial blood pressure. Finally, clots were treated with three r-tPA doses for different durations. Clot mass and mechanical behaviour was analysed to assess changes due to (i) Platelet driven contraction (ii) Compaction force and (iii) Thrombolysis. Clots that were exposed to r-tPA for longer duration showed significant reduction in clot mass (p < 0.001). Exposure time to r-tPA (p < 0.001) was shown to be an independent predictor of lower clot stiffness. A decrease in energy dissipation ratio during mechanical compression was associated with longer exposure time in r-tPA (p = 0.001) and a higher platelet concentration ratio (p = 0.018). The dose of r-tPA was not a significant factor in reducing clot mass or changing mechanical properties of the clots. Fibrinolysis reduces clot stiffness which may explain increased distal clot migration observed in patients treated with r-tPA and should be considered as a potential clot modification factor before mechanical thrombectomy.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Trombosis , Animales , Fibrinólisis , Humanos , Ovinos , Terapia Trombolítica , Trombosis/tratamiento farmacológicoRESUMEN
An acute ischaemic stroke appears when a blood clot blocks the blood flow in a cerebral artery. Intra-arterial thrombectomy, a mini-invasive procedure based on stent technology, is a mechanical available treatment to extract the clot and restore the blood circulation. After stent deployment, the clot, trapped in the stent struts, is pulled along with the stent towards a receiving catheter. Recent clinical trials have confirmed the effectiveness and safety of mechanical thrombectomy. However, the procedure requires further investigation. The aim of this study is the development of a numerical finite-element-based model of the thrombectomy procedure. In vitro thrombectomy tests are performed in different vessel geometries and one simulation for each test is carried out to verify the accuracy and reliability of the proposed numerical model. The results of the simulations confirm the efficacy of the model to replicate all the experimental setups. Clot stress and strain fields from the numerical analysis, which vary depending on the geometric features of the vessel, could be used to evaluate the possible fragmentation of the clot during the procedure. The proposed in vitro/in silico comparison aims at assessing the applicability of the numerical model and at providing validation evidence for the specific in vivo thrombectomy outcomes prediction.
RESUMEN
The aim of this work is to propose a methodology for identifying relationships between morphological features of the cerebral vasculature and the outcome of in silico simulations of thrombectomy, the mechanical treatment for acute ischemic stroke. Fourteen patient-specific cerebral vasculature segmentations were collected and used for geometric characterization of the intracranial arteries mostly affected by large vessel occlusions, i.e., internal carotid artery (ICA), middle cerebral artery (MCA) and anterior cerebral artery (ACA). First, a set of global parameters was created, including the geometrical information commonly provided in the clinical context, namely the total length, the average diameter and the tortuosity (length over head-tail distance) of the intracranial ICA. Then, a more exhaustive geometrical analysis was performed to collect a set of local parameters. A total of 27 parameters was measured from each patient-specific vascular configuration. Fourteen virtual thrombectomy simulations were performed with a blood clot with the same length and composition placed in the middle of the MCA. The model of TREVO ProVue stent-retriever was used for all the simulations. Results from simulations produced five unsuccessful outcomes, i.e., the clot was not removed from the vessels. The geometric parameters of the successful and unsuccessful simulations were compared to find relations between the vascular geometry and the outcome. None of the global parameters alone or combined proved able to discriminate between positive and negative outcome, while a combination of local parameters allowed to correctly identify the successful from the unsuccessful simulations. Although these results are limited by the number of patients considered, this study indicates a promising methodology to relate patient-specific geometry to virtual thrombectomy outcome, which might eventually guide decision making in the treatment of acute ischemic stroke.
RESUMEN
Treatment of acute ischemic stroke has been recently improved with the introduction of endovascular mechanical thrombectomy, a minimally invasive procedure able to remove a clot using aspiration devices and/or stent-retrievers. Despite the promising and encouraging results, improvements to the procedure and to the stent design are the focus of the recent efforts. Computational studies can pave the road to these improvements, providing their ability to describe and accurately reproduce a real procedure. A patient with ischemic stroke due to intracranial large vessel occlusion was selected and after the creation of the cerebral vasculature from computed tomography images and a histologic analysis to determine the clot composition, the entire thrombectomy procedure was virtually replicated. As in the real situation, the computational replica showed that two attempts were necessary to remove the clot, as a result of the position of the stent retriever with respect to the clot. Furthermore, the results indicated that clot fragmentation did not occur as the deformations were mainly in a compressive state without the possibility for clot cracks to propagate. The accurate representation of the procedure can be used as an important step for operative optimization planning and future improvements of stent designs.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Stents , Accidente Cerebrovascular/cirugía , Trombectomía , Resultado del TratamientoRESUMEN
: â BACKGROUND: Calcified cerebral emboli (CCEs) are a rare cause of acute ischemic stroke (AIS) and are frequently associated with poor outcomes. The presence of dense calcified material enables reliable identification of CCEs using non-contrast CT. However, recanalization rates with the available mechanical thrombectomy (MT) devices remain low. OBJECTIVE: To recreate a large vessel occlusion involving a CCE using an in vitro silicone model of the intracranial vessels and to demonstrate the feasability of this model to test different endovascular strategies to recanalize an occlusion of the M1 segment of the middle cerebral artery (MCA). : â METHODS: An in vitro model was developed to evaluate different endovascular treatment approaches using contemporary devices in the M1 segment of the MCA. The in vitro model consisted of a CCE analog placed in a silicone neurovascular model. Development of an appropriate CCE analog was based on characterization of human calcified tissues that represent likely sources of CCEs. Feasibility of the model was demonstrated in a small number of MT devices using four common procedural techniques. : â RESULTS: CCE analogs were developed with similar mechanical behavior to that of ex vivo calcified material. The in vitro model was evaluated with various MT techniques and devices to show feasibility of the model. In this limited evaluation, the most successful retrieval approach was performed with a stent retriever combined with local aspiration through a distal access catheter, and importantly, with flow arrest and dual aspiration using a balloon guide catheter. : â CONCLUSION: Characterization of calcified tissues, which are likely sources of CCEs, has shown that CCEs are considerably stiffer than thrombus. This highlights the need for a different in vitro AIS model for CCEs than those used for thromboemboli. Consequentially, an in vitro AIS model representative of a CCE occlusion in the M1 segment of the MCA has been developed.
Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Embolia Intracraneal/diagnóstico por imagen , Modelos Anatómicos , Accidente Cerebrovascular/diagnóstico por imagen , Trombectomía/métodos , Calcificación Vascular/diagnóstico por imagen , Anciano , Animales , Isquemia Encefálica/terapia , Femenino , Humanos , Embolia Intracraneal/terapia , Masculino , Ovinos , Accidente Cerebrovascular/terapia , Trombectomía/normas , Resultado del Tratamiento , Calcificación Vascular/terapia , Microtomografía por Rayos X/métodosRESUMEN
Carbon fibre reinforced PEEK (CF/PEEK) laminates provide mechanical advantages over homogenous metal osteo-synthesis implants, e.g. radiolucency, fatigue strength and strength to weight ratio. Implants can be designed with custom anisotropic material properties, thus enabling the engineer to tailor the overall stiffness of the implant to the specific loading conditions it will experience in vivo. In the current study a multi-scale computational investigation of idealised distal radius fracture fixation plate (DRP) is conducted. Physiological loading conditions are applied to macro-scale finite element models of DRPs. The mechanical response is compared for several CF/PEEK laminate layups to examine the effect of ply layup design. The importance of ply orientation in laminated DRPs is highlighted. A high number of 0° plies near the outer surfaces results in a greater bending strength while the addition of 45° plies increases the torsional strength of the laminates. Intra-laminar transverse tensile failure is predicted as the primary mode of failure. A micro-mechanical analysis of the CF/PEEK microstructure uncovers the precise mechanism under-lying intra-laminar transverse tensile crack to be debonding of the PEEK matrix from carbon fibres. Plastic strains in the matrix material are not sufficiently high to result in ductile failure of the matrix. The findings of this study demonstrate the significant challenge in the design and optimisation of fibre reinforced laminated composites for orthopaedic applications, highlighting the importance of multi-scale modelling for identification of failure mechanisms.
Asunto(s)
Fibra de Carbono/química , Análisis de Elementos Finitos , Fracturas Óseas/cirugía , Cetonas/química , Polietilenglicoles/química , Prótesis e Implantes , Radio (Anatomía)/lesiones , Benzofenonas , Calibración , Ensayo de Materiales , Polímeros , Resistencia a la TracciónRESUMEN
The active cytoskeleton is known to play an important mechanistic role in cellular structure, spreading, and contractility. Contractility is actively generated by stress fibres (SF), which continuously remodel in response to physiological dynamic loading conditions. The influence of actin-myosin cross-bridge cycling on SF remodelling under dynamic loading conditions has not previously been uncovered. In this study, a novel SF cross-bridge cycling model is developed to predict transient active force generation in cells subjected to dynamic loading. Rates of formation of cross-bridges within SFs are governed by the chemical potentials of attached and unattached myosin heads. This transient cross-bridge cycling model is coupled with a thermodynamically motivated framework for SF remodelling to analyse the influence of transient force generation on cytoskeletal evolution. A 1D implementation of the model is shown to correctly predict complex patterns of active cell force generation under a range of dynamic loading conditions, as reported in previous experimental studies.
Asunto(s)
Células/metabolismo , Fibras de Estrés/fisiología , Estrés Mecánico , Fenómenos Biomecánicos , Simulación por Computador , Elasticidad , Modelos Biológicos , Miosinas/metabolismo , Dinámicas no Lineales , Transducción de Señal , ViscosidadRESUMEN
Chlorination of 3-fluoro-2-methyl-aniline with N-chloro-succinimide gave one major regioisomer whose structure was determined by X-ray crystallography. The product was found to have cocrystallized with succinimide, giving the title compound, C(7)H(7)ClFN·C(4)H(5)NO(2). The crystal structure is stabilized by N-Hâ¯O hydrogen-bonding and π-π stacking inter-actions with a centroid-centroid distance of 3.4501â (8)â Å.