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1.
BMC Oral Health ; 24(1): 455, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622680

RESUMEN

BACKGROUND: The aim of this study is to evaluate the biomechanical behavior of the mesial and distal off-axial extensions of implant-retained prostheses in the posterior maxilla with different prosthetic materials using finite element analysis (FEA). METHODS: Three dimensional (3D) finite element models with three implant configurations and prosthetic designs (fixed-fixed, mesial cantilever, and distal cantilever) were designed and modelled depending upon cone beam computed tomography (CBCT) images of an intact maxilla of an anonymous patient. Implant prostheses with two materials; Monolithic zirconia (Zr) and polyetherketoneketone (PEKK) were also modeled .The 3D modeling software Mimics Innovation Suite (Mimics 14.0 / 3-matic 7.01; Materialise, Leuven, Belgium) was used. All the models were imported into the FE package Marc/Mentat (ver. 2015; MSC Software, Los Angeles, Calif). Then, individual models were subjected to separate axial loads of 300 N. Von mises stress values were computed for the prostheses, implants, and bone under axial loading. RESULTS: The highest von Mises stresses in implant (111.6 MPa) and bone (100.0 MPa) were recorded in distal cantilever model with PEKK material, while the lowest values in implant (48.9 MPa) and bone (19.6 MPa) were displayed in fixed fixed model with zirconia material. The distal cantilever model with zirconia material yielded the most elevated levels of von Mises stresses within the prosthesis (105 MPa), while the least stresses in prosthesis (35.4 MPa) were recorded in fixed fixed models with PEKK material. CONCLUSIONS: In the light of this study, the combination of fixed fixed implant prosthesis without cantilever using a rigid zirconia material exhibits better biomechanical behavior and stress distribution around bone and implants. As a prosthetic material, low elastic modulus PEKK transmitted more stress to implants and surrounding bone especially with distal cantilever.


Asunto(s)
Implantes Dentales , Circonio , Humanos , Análisis de Elementos Finitos , Maxilar/cirugía , Prótesis Dental de Soporte Implantado , Análisis del Estrés Dental/métodos , Estrés Mecánico
2.
Soft Matter ; 20(16): 3425-3435, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38623617

RESUMEN

Understanding the interactions of pathogenic droplets with surfaces is crucial to biomedical applications. In this study, using E. coli as the model microbe, we investigate the impact of a bacteria-laden droplet on different substrates, both bare and antimicrobial. In doing so, we unveil the significance of kinetic energy and spreading parameters of the impacting droplet in determining the microbes' proliferation capabilities. Our results indicate an inverse relationship between the impact Weber number and the bacterial ability to proliferate. We reveal that the mechanical stress generated during impact impedes the capabilities of microbes present inside the droplet to create their progeny. Following an order analysis of the mechanical stress generated, we argue that the impact does not induce lysis-driven cell death of the bacteria; rather, it promotes a stress-driven transition of viable bacteria to a viable-but-non-culturable (VBNC) state. Furthermore, variations in the concentration of particles on the antimicrobial surfaces revealed the role of the post-impact spreading behaviour in dictating bacterial proliferation capabilities. Contrary to the conventional notion, we demonstrate that during the early stages of interaction, a bare substrate may outperform an antibacterial substrate in the inactivation of the bacterial load. Finally, we present an interaction map illustrating the complex relationship between bacterial colony-forming units, bactericide concentration on the surface, and the impact Weber number. We believe that the inferences of the study, highlighting the effect of mechanical stresses on the soft cell wall of microbes, could be a useful design consideration for the development of antimicrobial surfaces.


Asunto(s)
Escherichia coli , Propiedades de Superficie , Escherichia coli/fisiología , Escherichia coli/efectos de los fármacos , Estrés Mecánico , Antibacterianos/farmacología , Antibacterianos/química
3.
PLoS One ; 19(4): e0297381, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38635828

RESUMEN

The new thermal insulating shotcrete is of great significance for the management of thermal damage in deep mines, and its own strength has a greater impact on the roadway insulation and safe production, so it is very necessary to study the shear strength of the new thermal insulating shotcrete under the influence of the deep hot and humid environment and the stress of mining. For the heat-insulating shotcrete, firstly, we carried out the concrete variable angle shear test under different loading rates, which concluded that the shear rate and peak shear stress showed a trend of increasing and then decreasing; as the angle increases, the different rates have a greater impact on the peak shear stress of the specimen. Secondly, the concrete variable angle shear test was carried out under the temperature and humidity cycle, which revealed that the shear strength of thermal insulated shotcrete increased firstly and then decreased with the increase of temperature at the same number of cycles. Finally, the empirical equations between the cohesive force c, the angle of internal friction ϕ and the number of warm and wet cycles n and the temperature of warm and wet cycles T are fitted with the MATLAB software respectively, and the research results provide technical references for the management of geothermal temperature in deep well projects.


Asunto(s)
Calor , Temperatura , Humedad , Estrés Mecánico
4.
J Dent Res ; 103(5): 555-564, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38594786

RESUMEN

The temporomandibular joint (TMJ) disc is mainly composed of collagen, with its arrangement responding to efficient stress distribution. However, microstructural and micromechanical transformations of the TMJ disc under resting, functional, and pathological conditions remain unclear. To address this, our study presents a high-resolution microstructural and mechanical atlas of the porcine TMJ disc. First, the naive microstructure and mechanical properties were investigated in porcine TMJ discs (resting and functional conditions). Subsequently, the perforation and tear models (pathological conditions) were compared. Following this, a rabbit model of anterior disc displacement (abnormal stress) was studied. Results show diverse microstructures and mechanical properties at the nanometer to micrometer scale. In the functional state, gradual unfolding of the crimping cycle in secondary and tertiary structures leads to D-cycle prolongation in the primary structure, causing tissue failure. Pathological conditions lead to stress concentration near the injury site due to collagen interfibrillar traffic patterns, resulting in earlier damage manifestation. Additionally, the abnormal stress model shows collagen damage initiating at the primary structure and extending to the superstructure over time. These findings highlight collagen's various roles in different pathophysiological states. Our study offers valuable insights into TMJ disc function and dysfunction, aiding the development of diagnostic and therapeutic strategies for TMJ disorders, as well as providing guidance for the design of structural biomimetic materials.


Asunto(s)
Disco de la Articulación Temporomandibular , Animales , Disco de la Articulación Temporomandibular/fisiopatología , Conejos , Porcinos , Fenómenos Biomecánicos , Colágeno , Estrés Mecánico , Modelos Animales de Enfermedad , Trastornos de la Articulación Temporomandibular/fisiopatología , Trastornos de la Articulación Temporomandibular/patología
5.
Sci Rep ; 14(1): 8984, 2024 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637544

RESUMEN

The influence of the aneurysm evolution on the hemodynamic characteristic of the blood flow inside the sac region is comprehensively investigated. By using the computational method, the blood flow through the vessel and aneurysm of the sac region is examined to find the role of aneurysm evolution on the wall shear stress, pressure, and risk of aneurysm rupture. Three different models of ICA aneurysms are chosen for the investigation of the aneurysm evolution at risk of rupture. Obtained data shows that the evolution of the aneurysm decreases the wall shear stress and pressure on the sac surface while an oscillatory index of blood increases on the aneurysm wall.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Accidente Cerebrovascular , Humanos , Hemodinámica/fisiología , Estrés Mecánico
6.
J Orthop Surg Res ; 19(1): 257, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649946

RESUMEN

BACKGROUND: The mechanotransduction mechanisms by which cells regulate tissue remodeling are not fully deciphered. Circular RNAs (circRNAs) are crucial to various physiological processes, including cell cycle, differentiation, and polarization. However, the effects of mechanical force on circRNAs and the role of circRNAs in the mechanobiology of differentiation and remodeling in stretched periodontal ligament stem cells (PDLSCs) remain unclear. This article aims to explore the osteogenic function of mechanically sensitive circular RNA protein kinase D3 (circPRKD3) and elucidate its underlying mechanotransduction mechanism. MATERIALS AND METHODS: PDLSCs were elongated with 8% stretch at 0.5 Hz for 24 h using the Flexcell® FX-6000™ Tension System. CircPRKD3 was knockdown or overexpressed with lentiviral constructs or plasmids. The downstream molecules of circPRKD3 were predicted by bioinformatics analysis. The osteogenic effect of related molecules was evaluated by quantitative real-time PCR (qRT-PCR) and western blot. RESULTS: Mechanical force enhanced the osteogenesis of PDLSCs and increased the expression of circPRKD3. Knockdown of circPRKD3 hindered PDLSCs from osteogenesis under mechanical force, while overexpression of circPRKD3 promoted the early osteogenesis process of PDLSCs. With bioinformatics analysis and multiple software predictions, we identified hsa-miR-6783-3p could act as the sponge of circPRKD3 to indirectly regulate osteogenic differentiation of mechanically stimulated PDLSCs. CONCLUSIONS: Our results first suggested that both circPRKD3 and hsa-miR-6783-3p could enhance osteogenesis of stretched PDLSCs. Furthermore, hsa-miR-6783-3p could sponge circPRKD3 to indirectly regulate RUNX2 during the periodontal tissue remodeling process in orthodontic treatment.


Asunto(s)
MicroARNs , Osteogénesis , Ligamento Periodontal , ARN Circular , Células Madre , Ligamento Periodontal/citología , Osteogénesis/genética , Osteogénesis/fisiología , Humanos , ARN Circular/genética , ARN Circular/fisiología , MicroARNs/genética , Células Madre/metabolismo , Células Cultivadas , Mecanotransducción Celular/fisiología , Diferenciación Celular/genética , Estrés Mecánico , Proteínas Serina-Treonina Quinasas/genética
7.
Soft Matter ; 20(16): 3401-3410, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38563244

RESUMEN

Living active collectives have evolved with remarkable self-patterning capabilities to adapt to the physical and biological constraints crucial for their growth and survival. However, the intricate process by which complex multicellular patterns emerge from a single founder cell remains elusive. In this study, we utilize an agent-based model, validated through single-cell microscopy imaging, to track the three-dimensional (3D) morphodynamics of cells within growing bacterial biofilms encased by agarose gels. The confined growth conditions give rise to a spatiotemporally heterogeneous stress landscape within the biofilm. In the core of the biofilm, where high hydrostatic and low shear stresses prevail, cell packing appears disordered. In contrast, near the gel-cell interface, a state of high shear stress and low hydrostatic stress emerges, driving nematic ordering, albeit with a time delay inherent to shear stress relaxation. Strikingly, we observe a robust spatiotemporal correlation between stress anisotropy and nematic ordering within these confined biofilms. This correlation suggests a mechanism whereby stress anisotropy plays a pivotal role in governing the spatial organization of cells. The reciprocity between stress anisotropy and cell ordering in confined biofilms opens new avenues for innovative 3D mechanically guided patterning techniques for living active collectives, which hold significant promise for a wide array of environmental and biomedical applications.


Asunto(s)
Biopelículas , Estrés Mecánico , Anisotropía , Modelos Biológicos
8.
Arterioscler Thromb Vasc Biol ; 44(5): 1065-1085, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38572650

RESUMEN

Blood vessels are subjected to complex biomechanical loads, primarily from pressure-driven blood flow. Abnormal loading associated with vascular grafts, arising from altered hemodynamics or wall mechanics, can cause acute and progressive vascular failure and end-organ dysfunction. Perturbations to mechanobiological stimuli experienced by vascular cells contribute to remodeling of the vascular wall via activation of mechanosensitive signaling pathways and subsequent changes in gene expression and associated turnover of cells and extracellular matrix. In this review, we outline experimental and computational tools used to quantify metrics of biomechanical loading in vascular grafts and highlight those that show potential in predicting graft failure for diverse disease contexts. We include metrics derived from both fluid and solid mechanics that drive feedback loops between mechanobiological processes and changes in the biomechanical state that govern the natural history of vascular grafts. As illustrative examples, we consider application-specific coronary artery bypass grafts, peripheral vascular grafts, and tissue-engineered vascular grafts for congenital heart surgery as each of these involves unique circulatory environments, loading magnitudes, and graft materials.


Asunto(s)
Prótesis Vascular , Hemodinámica , Humanos , Animales , Modelos Cardiovasculares , Falla de Prótesis , Estrés Mecánico , Fenómenos Biomecánicos , Mecanotransducción Celular , Implantación de Prótesis Vascular/efectos adversos , Diseño de Prótesis , Oclusión de Injerto Vascular/fisiopatología , Oclusión de Injerto Vascular/etiología , Remodelación Vascular
9.
Nat Cell Biol ; 26(4): 519-529, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38570617

RESUMEN

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.


Asunto(s)
Incisivo , Transducción de Señal , Animales , Femenino , Embarazo , Diferenciación Celular , Mamíferos , Proliferación Celular , Estrés Mecánico
10.
Lab Chip ; 24(8): 2347-2357, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38576401

RESUMEN

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and an important contributor to morbidity and mortality. Endothelial dysfunction has been postulated to be an important contributing factor in cardiovascular events in patients with AF. However, how vascular endothelial cells respond to arrhythmic flow is not fully understood, mainly due to the limitation of current in vitro systems to mimic arrhythmic flow conditions. To address this limitation, we developed a microfluidic system to study the effect of arrhythmic flow on the mechanobiology of human aortic endothelial cells (HAECs). The system utilises a computer-controlled piezoelectric pump for generating arrhythmic flow with a unique ability to control the variability in both the frequency and amplitude of pulse waves. The flow rate is modulated to reflect physiological or pathophysiological shear stress levels on endothelial cells. This enabled us to systematically dissect the importance of variability in the frequency and amplitude of pulses and shear stress level on endothelial cell mechanobiology. Our results indicated that arrhythmic flow at physiological shear stress level promotes endothelial cell spreading and reduces the plasma membrane-to-cytoplasmic distribution of ß-catenin. In contrast, arrhythmic flow at low and atherogenic shear stress levels does not promote endothelial cell spreading or redistribution of ß-catenin. Interestingly, under both shear stress levels, arrhythmic flow induces inflammation by promoting monocyte adhesion via an increase in ICAM-1 expression. Collectively, our microfluidic system provides opportunities to study the effect of arrhythmic flows on vascular endothelial mechanobiology in a systematic and reproducible manner.


Asunto(s)
Células Endoteliales , beta Catenina , Humanos , beta Catenina/metabolismo , Microfluídica , Aorta , Inflamación/metabolismo , Estrés Mecánico , Células Cultivadas
11.
J Mech Behav Biomed Mater ; 154: 106520, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38569421

RESUMEN

The preparation of slender specimens for in-vitro tissue characterisation could potentially alter mechanical tissue properties. To investigate this factor, rectangular specimens were prepared from the wall of the porcine aorta for uniaxial tensile loading. Varying strip widths of 16 mm, 8 mm, and 4 mm were achieved by excising zero, one, and three cuts within the specimen along the loading direction, respectively. While specimens loaded along the vessel's circumferential direction acquired consistent tissue properties, the width of test specimens influenced the results of axially loaded tissue; vascular wall stiffness was reduced by approximately 40% in specimens with strips 4 mm wide. In addition, the cross-loading stretch was strongly influenced by specimen strip width, and fiber sliding contributed to the softening of slender tensile specimens, an outcome from finite element analysis of test specimens. We may, therefore, conclude that cutting orthogonal to the main direction of collagen fibers introduces mechanical trauma that weakens slender tensile specimens, compromising the determination of representative mechanical vessel wall properties.


Asunto(s)
Aorta , Porcinos , Animales , Resistencia a la Tracción , Análisis de Elementos Finitos , Estrés Mecánico , Fenómenos Biomecánicos
12.
PLoS One ; 19(4): e0300326, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38626003

RESUMEN

This study aimed to reduce the risk of graft occlusion by evaluating the two-phase flow of blood and LDL nanoparticles in coronary artery grafts. The study considered blood as an incompressible Newtonian fluid, with the addition of LDL nanoparticles, and the artery wall as a porous medium. Two scenarios were compared, with constant inlet velocity (CIV) and other with pulsatile inlet velocity (PIV), with LDL nanoparticles experiencing drag, wall-induced lift, and induced Saffman lift forces, or drag force only. The study also evaluated the concentration polarization of LDLs (CP of LDLs) near the walls, by considering the artery wall with and without permeation. To model LDL nanoparticles, the study randomly injected 100, 500, and 1000 nanoparticles in three release states at each time step, using different geometries. Numerical simulations were performed using COMSOL software, and the results were presented as relative collision of nanoparticles to the walls in tables, diagrams, and shear stress contours. The study found that a graft implantation angle of 15° had the most desirable conditions compared to larger angles, in terms of nanoparticle collision with surfaces and occlusion. The nanoparticle release modes behaved similarly in terms of collision with the surfaces. A difference was observed between CIV and PIV. Saffman lift and wall-induced lift forces having no effect, possibly due to the assumption of a porous artery wall and perpendicular outlet flow. In case of permeable artery walls, relative collision of particles with the graft wall was larger, suggesting the effect of CP of LDLs.


Asunto(s)
Bahías , Vasos Coronarios , Simulación por Computador , Porosidad , Modelos Cardiovasculares , Velocidad del Flujo Sanguíneo , Estrés Mecánico
13.
Comput Methods Programs Biomed ; 249: 108144, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38569255

RESUMEN

OBJECTIVE: Iatrogenic coronary artery dissection is a complication of coronary intimal injury and dissection due to improper catheter manipulation. The impact of tear direction on the prognosis of coronary artery dissection (CAD) remains unclear. This study examines the hemodynamic effects of different tear directions (transverse and longitudinal) of CAD and evaluates the risk of thrombosis, rupture and further dilatation of CAD. METHODS: Two types of CAD models (Type I: transverse tear, Type II: longitudinal tear) were reconstructed from the aorto-coronary CTA dataset of 8 healthy cases. Four WSS-based indicators were analyzed, including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and cross flow index (CFI). A thrombus growth model was also introduced to predict the trend of thrombus growth in CAD with two different tear directions. RESULTS: For most of the WSS-based indicators, including TAWSS, RRT, and CFI, no statistically significant differences were observed across the CAD models with varying tear directions, except for OSI, where a significant difference was noted (p < 0.05). Meanwhile, in terms of thrombus growth, the thrombus growing at the tear of the Type I (transverse tear) CAD model extended into the true lumen earlier than that of the Type II (longitudinal tear) model. CONCLUSIONS: Numerical simulations suggest that: (1) The CAD with transverse tear have a high risk of further tearing of the dissection at the distal end of the tear. (2) The CAD with longitudinal tear create a hemodynamic environment characterized by low TAWSS and high OSI in the false lumen, which may additionally increase the risk of vessel wall injury. (3) The CAD with transverse tear may have a higher risk of thrombosis and coronary obstruction and myocardial ischemia in the early phase of the dissection.


Asunto(s)
Disección Aórtica , Trombosis , Humanos , Vasos Coronarios/diagnóstico por imagen , Modelos Cardiovasculares , Hemodinámica , Enfermedad Crónica , Trombosis/etiología , Estrés Mecánico
14.
J Biomech Eng ; 146(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38584416

RESUMEN

Aging is a primary risk factor for degenerative tendon injuries, yet the etiology and progression of this degeneration are poorly understood. While aged tendons have innate cellular differences that support a reduced ability to maintain mechanical tissue homeostasis, the response of aged tendons to altered levels of mechanical loading has not yet been studied. To address this question, we subjected young and aged murine flexor tendon explants to various levels of in vitro tensile strain. We first compared the effect of static and cyclic strain on matrix remodeling in young tendons, finding that cyclic strain is optimal for studying remodeling in vitro. We then investigated the remodeling response of young and aged tendon explants after 7 days of varied mechanical stimulus (stress deprivation, 1%, 3%, 5%, or 7% cyclic strain) via assessment of tissue composition, biosynthetic capacity, and degradation profiles. We hypothesized that aged tendons would show muted adaptive responses to changes in tensile strain and exhibit a shifted mechanical setpoint, at which the remodeling balance is optimal. Interestingly, we found that 1% cyclic strain best maintains native physiology while promoting extracellular matrix (ECM) turnover for both age groups. However, aged tendons display fewer strain-dependent changes, suggesting a reduced ability to adapt to altered levels of mechanical loading. This work has a significant impact on understanding the regulation of tissue homeostasis in aged tendons, which can inform clinical rehabilitation strategies for treating elderly patients.


Asunto(s)
Traumatismos de los Tendones , Tendones , Humanos , Ratones , Animales , Anciano , Estrés Mecánico , Tendones/fisiología , Matriz Extracelular , Envejecimiento
15.
J Biomech ; 167: 112071, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38593721

RESUMEN

Ligaments and tendons undergo nonuniform deformation during movement. While deformations can be imaged, it remains challenging to use such information to infer regional tissue loading. Shear wave tensiometry is a promising noninvasive technique to gauge axial stress and is premised on a tensioned beam model. However, it is unknown whether tensiometry can predict regional stress in a nonuniformly loaded structure. The objectives of this study were to (1) determine whether regional shear wave speed tracks regional axial stress in nonuniformly loaded fibrous soft tissues, and (2) determine the sensitivity of regional axial stress and shear wave speed to nonuniform load distribution and fiber alignment. We created a representative set of 12,000 dynamic finite element models of a fibrous soft tissue with probabilistic variations in fiber alignment, stiffness, and aspect ratio. In each model, we applied a randomly selected nonuniform load distribution, and then excited a shear wave and tracked its regional propagation. We found that regional shear wave speed was an excellent predictor of the regional axial stress (RMSE = 0.57 MPa) and that the nature of the regional shear wave speed-stress relationship was consistent with a tensioned beam model (R2 = 0.99). Variations in nonuniform load distribution and fiber alignment did not substantially alter the wave speed-stress relationship, particularly at higher loads. Thus, these findings suggests that shear wave tensiometry could provide a quantitative estimate of regional tissue stress in ligaments and tendons.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Tendones , Movimiento , Ligamentos , Estrés Mecánico , Carmustina , Etopósido
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 532-540, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-38660863

RESUMEN

OBJECTIVE: To investigate the molecular mechanism of proteolytic cleavage of unusually large von Willebrand Factor(ULVWF) on endothelial cells by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) in the absence of fluid shear stress, so as to provide a theoretical basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) and other thrombotic disorders. METHODS: The ADAMTS13-mediated proteolysis of ULVWF on the surface of endothelial cells in the absence of fluid shear stress was observed through immunofluorescence microscopy. The variation in VWF antigen levels in the conditioned media were determined by ELISA assay. The levels of VWF and the proteolytic fragments released into the conditioned media were determined by ELISA assay and Western blot in the absence and presence of fluid shear stress or FVIII. The effect of ADAMTS13-mediated ULVWF cleavage on the normal distribution of plasma VWF multimers was evaluated by multimer analysis. Histamine stimulated human umbilical vein endothelial cells (HUVECs) were incubated with ADAMTS13 and various N- and C-terminally truncated mutants. Then the ULVWF that maintained binding to the cells were observed through immunofluorescence microscopy and the soluble ULVWF released from endothelial cells was determined by ELISA, so as to demonstrate the domains of ADAMTS13 required for proteolysis of ULVWF on endothelial cells. RESULTS: The ULVWF strings on the endothelial cell surface were rapidly proteolyzed by recombinant and plasma ADAMTS13 in the absence of fluid shear stress. This proteolytic processing of ULVWF depended on incubation time and ADAMTS13 concentration, but not shear stress and FVIII. The distribution of VWF releaseded by ADAMTS13-mediated proteolysis was quite similar to that secreted by endothelial cells under histamine stimulation, suggesting the ULVWF cleavage occured at the cell surface. The proteolysis of the ULVWF on endothelial cells required the Cys-rich(CysR) and spacer domains, but not the TSP1 2-8 and CUB domains of ADAMTS13. CONCLUSION: The ULVWF polymers on endothelial cells are sensitive to ADAMTS13-mediated cleavage even in the absence of fluid shear stress. The findings provide novel insight into the molecular mechanism of ADAMTS13-mediated ULVWF cleavage at the cellular level and may contribute to understanding of the pathogenesis of TTP and other thrombotic disorders.


Asunto(s)
Proteína ADAMTS13 , Células Endoteliales , Células Endoteliales de la Vena Umbilical Humana , Proteolisis , Estrés Mecánico , Factor de von Willebrand , Humanos , Factor de von Willebrand/metabolismo , Proteína ADAMTS13/metabolismo , Células Endoteliales/metabolismo , Proteínas ADAM/metabolismo , Púrpura Trombocitopénica Trombótica/metabolismo
17.
PLoS One ; 19(4): e0301350, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38626136

RESUMEN

Bicuspid aortic valve (BAV) is the most common cardiac congenital abnormality with a high rate of concomitant aortic valve and ascending aorta (AAo) pathologic changes throughout the patient's lifetime. The etiology of BAV-related aortopathy was historically believed to be genetic. However, recent studies theorize that adverse hemodynamics secondary to BAVs also contribute to aortopathy, but their precise role, specifically, that of wall shear stress (WSS) magnitude and directionality remains controversial. Moreover, the primary therapeutic option for BAV patients is aortic valve replacement (AVR), but the role of improved post-AVR hemodynamics on aortopathy progression is also not well-understood. To address these issues, this study employs a computational fluid dynamics model to simulate personalized AAo hemodynamics before and after TAVR for a small cohort of 6 Left-Right fused BAV patients. Regional distributions of five hemodynamic metrics, namely, time-averaged wall shear stress (TAWSS) and oscillating shear index (OSI), divergence of wall shear (DWSS), helicity flux integral & endothelial cell activation potential (ECAP), which are hypothesized to be associated with potential aortic injury are computed in the root, proximal and distal ascending aorta. BAVs are characterized by strong, eccentric jets, with peak velocities exceeding 4 m/s and axially circulating flow away from the jets. Such conditions result in focused WSS loading along jet attachment regions on the lumen boundary and weaker, oscillating WSS on other regions. The jet attachment regions also show alternating streaks of positive and negative DWSS, which may increase risk for local tissue stretching. Large WSS magnitudes, strong helical flows and circumferential WSS have been previously implicated in the progression of BAV aortopathy. Post-intervention hemodynamics exhibit weaker, less eccentric jets. Significant reductions are observed in flow helicity, TAWSS and DWSS in localized regions of the proximal AAo. On the other hand, OSI increases post-intervention and ECAP is observed to be low in both pre- and post-intervention scenarios, although significant increases are also observed in this ECAP. These results indicate a significant alleviation of pathological hemodynamics post AVR.


Asunto(s)
Enfermedad de la Válvula Aórtica Bicúspide , Enfermedades de las Válvulas Cardíacas , Humanos , Enfermedades de las Válvulas Cardíacas/complicaciones , Aorta/patología , Válvula Aórtica/fisiología , Hemodinámica/fisiología , Estrés Mecánico
18.
J Nanobiotechnology ; 22(1): 187, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632623

RESUMEN

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions.


Asunto(s)
Microfluídica , Trombosis , Humanos , Células Endoteliales , Línea Celular , Trombosis/patología , Estrés Mecánico
19.
BMC Musculoskelet Disord ; 25(1): 318, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654258

RESUMEN

BACKGROUND: Non-contact anterior cruciate ligament (ACL) injuries are a major concern in sport-related activities due to dynamic knee movements. There is a paucity of finite element (FE) studies that have accurately replicated the knee geometry, kinematics, and muscle forces during dynamic activities. The objective of this study was to develop and validate a knee FE model and use it to quantify the relationships between sagittal plane knee kinematics, kinetics and the resulting ACL strain. METHODS: 3D images of a cadaver knee specimen were segmented (bones, cartilage, and meniscus) and meshed to develop the FE model. Knee ligament insertion sites were defined in the FE model via experimental digitization of the specimen's ligaments. The response of the model was validated against multiple physiological knee movements using published experimental data. Single-leg jump landing motions were then simulated on the validated model with muscle forces and kinematic inputs derived from motion capture and rigid body modelling of ten participants. RESULTS: The maximum ACL strain measured with the model during jump landing was 3.5 ± 2.2%, comparable to published experimental results. Bivariate analysis showed no significant correlation between body weight, ground reaction force and sagittal plane parameters (such as joint flexion angles, joint moments, muscle forces, and joint velocity) and ACL strain. Multivariate regression analysis showed increasing trunk, hip and ankle flexion angles decreases ACL strain (R2 = 90.04%, p < 0.05). CONCLUSIONS: Soft landing decreases ACL strain and the relationship could be presented through an empirical equation. The model and the empirical relation developed in this study could be used to better predict ACL injury risk and prevention strategies during dynamic activities.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Humanos , Ligamento Cruzado Anterior/fisiología , Fenómenos Biomecánicos/fisiología , Masculino , Lesiones del Ligamento Cruzado Anterior/fisiopatología , Lesiones del Ligamento Cruzado Anterior/prevención & control , Lesiones del Ligamento Cruzado Anterior/etiología , Articulación de la Rodilla/fisiología , Cadáver , Simulación por Computador , Análisis de Elementos Finitos , Adulto , Femenino , Movimiento/fisiología , Adulto Joven , Persona de Mediana Edad , Estrés Mecánico , Músculo Esquelético/fisiología , Modelos Biológicos
20.
J R Soc Interface ; 21(213): 20230592, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38593841

RESUMEN

The mechanical characterization of the oesophagus is essential for applications such as medical device design, surgical simulations and tissue engineering, as well as for investigating the organ's pathophysiology. However, the material response of the oesophagus has not been established ex vivo in regard to the more complex aspects of its mechanical behaviour using fresh, human tissue: as of yet, in the literature, only the hyperelastic response of the intact wall has been studied. Therefore, in this study, the layer-dependent, anisotropic, visco-hyperelastic behaviour of the human oesophagus was investigated through various mechanical tests. For this, cyclic tests, with increasing stretch levels, were conducted on the layers of the human oesophagus in the longitudinal and circumferential directions and at two different strain rates. Additionally, stress-relaxation tests on the oesophageal layers were carried out in both directions. Overall, the results show discrete properties in each layer and direction, highlighting the importance of treating the oesophagus as a multi-layered composite material with direction-dependent behaviour. Previously, the authors conducted layer-dependent cyclic experimentation on formalin-embalmed human oesophagi. A comparison between the fresh and embalmed tissue response was carried out and revealed surprising similarities in terms of anisotropy, strain-rate dependency, stress-softening and hysteresis, with the main difference between the two preservation states being the magnitude of these properties. As formalin fixation is known to notably affect the formation of cross-links between the collagen of biological materials, the differences may reveal the influence of cross-links on the mechanical behaviour of soft tissues.


Asunto(s)
Esófago , Proyectos de Investigación , Humanos , Estrés Mecánico , Esófago/fisiología , Anisotropía , Fenómenos Biomecánicos , Resistencia a la Tracción
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