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1.
J Biomech ; 157: 111725, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37459752

RESUMO

Musculoskeletal modeling has been effective for simulating dexterity and exploring the consequences of disability. While previous approaches have examined motor function using multibody dynamics, existing musculoskeletal models of the hand and fingers have difficulty simulating soft tissue such as the extensor mechanism of the fingers, which remains underexplored. To investigate the extensor mechanism and its impact on finger motor function, we developed a finite element model of the index finger extensor mechanism and a cosimulation method that combines the finite element model with a multibody dynamic model. The finite element model and cosimulation were validated through comparison with experimentally derived tissue strains and fingertip endpoint forces respectively. Tissue strains predicted by the finite element model were consistent with the experimentally observed strains of the 9 postures tested in cadaver specimens. Fingertip endpoint forces predicted using the cosimulation were well aligned in both force (difference within 0.60 N) and direction (difference within 30°with experimental results. Sensitivity of the extensor mechanism to changes in modulus and adhesion configuration were evaluated for ± 50% of experimental moduli, presence of the radial and ulnar adhesions, and joint capsule. Simulated strains and endpoint forces were found to be minimally sensitive to alterations in moduli and adhesions. These results are promising and demonstrate the ability of the cosimulation to predict global behavior of the extensor mechanism, while enabling measurement of stresses and strains within the structure itself. This model could be used in the future to predict the outcomes for different surgical repairs of the extensor mechanism.


Assuntos
Modelos Biológicos , Tendões , Análise de Elementos Finitos , Dedos , Mãos , Fenômenos Biomecânicos
2.
Inhal Toxicol ; 35(7-8): 214-229, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37339372

RESUMO

BACKGROUND: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. RESULTS: The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. CONCLUSION: The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.


Assuntos
Amiantos Anfibólicos , Amianto , Ratos , Animais , Amiantos Anfibólicos/toxicidade , Fibras Minerais , Aerossóis , Exposição por Inalação/efeitos adversos
3.
Inhal Toxicol ; 35(7-8): 201-213, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37339371

RESUMO

BACKGROUND: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project. RESULTS: A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for in vivo inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically. CONCLUSIONS: Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for in vivo inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007.


Assuntos
Amiantos Anfibólicos , Amianto , Humanos , Ratos , Animais , Amiantos Anfibólicos/toxicidade , Fibras Minerais , Amianto/análise , Carcinógenos/toxicidade , Aerossóis
4.
J Neurosurg Pediatr ; 29(2): 218-224, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34678779

RESUMO

OBJECTIVE: The underlying biomechanical differences between the pediatric and adult cervical spine are incompletely understood. Computational spine modeling can address that knowledge gap. Using a computational method known as finite element modeling, the authors describe the creation and evaluation of a complete pediatric cervical spine model. METHODS: Using a thin-slice CT scan of the cervical spine from a 5-year-old boy, a 3D model was created for finite element analysis. The material properties and boundary and loading conditions were created and model analysis performed using open-source software. Because the precise material properties of the pediatric cervical spine are not known, a published parametric approach of scaling adult properties by 50%, 25%, and 10% was used. Each scaled finite element model (FEM) underwent two types of simulations for pediatric cadaver testing (axial tension and cardinal ranges of motion [ROMs]) to assess axial stiffness, ROM, and facet joint force (FJF). The authors evaluated the axial stiffness and flexion-extension ROM predicted by the model using previously published experimental measurements obtained from pediatric cadaveric tissues. RESULTS: In the axial tension simulation, the model with 50% adult ligamentous and annulus material properties predicted an axial stiffness of 49 N/mm, which corresponded with previously published data from similarly aged cadavers (46.1 ± 9.6 N/mm). In the flexion-extension simulation, the same 50% model predicted an ROM that was within the range of the similarly aged cohort of cadavers. The subaxial FJFs predicted by the model in extension, lateral bending, and axial rotation were in the range of 1-4 N and, as expected, tended to increase as the ligament and disc material properties decreased. CONCLUSIONS: A pediatric cervical spine FEM was created that accurately predicts axial tension and flexion-extension ROM when ligamentous and annulus material properties are reduced to 50% of published adult properties. This model shows promise for use in surgical simulation procedures and as a normal comparison for disease-specific FEMs.

5.
Spine J ; 21(1): 150-159, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768656

RESUMO

BACKGROUND CONTEXT: Previous studies have analyzed the effect of laminectomy on intervertebral disc (IVD), facet-joint-forces (FJF), and range of motion (ROM), while only two have specifically reported stresses at the pars interarticularis (PI) with posterior element resection. These studies have been performed utilizing a single subject, questioning their applications to a broader population. PURPOSE: We investigate the effect of graded PI resection in a three-dimensional manner on PI stress to provide surgical guidelines for avoidance of iatrogenic instability following lumbar laminectomy. Additionally, quantified FJF and IVD stresses can provide further insight into the development of adjacent segment disease. STUDY DESIGN: Biomechanical finite element (FE) method investigation of the lumbar spine. METHODS: FE models of the lumbar spine of three subjects were created using the open-source finite element software, FEBio. Single-level laminectomy, two-level laminectomy, and ventral-to-dorsal PI resection simulations were performed with varying degrees of PI resection from 0% to 75% of the native PI. These models were taken through cardinal ROM under standard loading conditions and PI stresses, FJF, IVD stresses, and ROM were analyzed. RESULTS: The three types of laminectomy simulated in this study showed a nonlinear increase in PI stress with increased bone resection. Axial rotation generated the most stress at the PI followed by flexion, extension and lateral bending. At 75% bone resection all three types of laminectomy produced PI stresses that were near the ultimate strength of human cortical bone during axial rotation. FJF decreased with increased bone resection for the three laminectomies simulated. This was most notable in axial rotation followed by extension and lateral bending. IVD stresses varied greatly between the nonsurgical models and likewise the effect of laminectomy on IVD stresses varied between subjects. ROM was mostly unaffected by the laminectomies performed in this study. CONCLUSIONS: Regarding the risk of iatrogenic spondylolisthesis, the combined results are sufficient evidence to suggest surgeons should be particularly cautious when PI resection exceeds 50% bone resection for all laminectomies included in this study. Lastly, the effects seen in FJF and IVD stresses indicate the degree to which the remainder of the spine must experience compensatory biomechanical changes as a result of the surgical intervention.


Assuntos
Laminectomia , Vértebras Lombares , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Laminectomia/efeitos adversos , Vértebras Lombares/cirurgia , Amplitude de Movimento Articular
6.
J Biomech ; 113: 110077, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33142209

RESUMO

Finite element (FE) analysis has proven to be useful when studying the biomechanics of the cervical spine. Although many FE studies of the cervical spine have been published, they typically develop their models using commercial software, making the sharing of models between researchers difficult. They also often model only one part of the cervical spine. The goal of this study was to develop and evaluate three FE models of the adult cervical spine using open-source software and to freely provide these models to the scientific community. The models were created from computed tomography scans of 26-, 59-, and 64-year old female subjects. These models were evaluated against previously published experimental and FE data. Despite the fact that all three models were assigned identical material properties and boundary conditions, there was notable variation in their biomechanical behavior. It was therefore apparent that these differences were the result of morphological differences between the models.


Assuntos
Vértebras Cervicais , Software , Adulto , Fenômenos Biomecânicos , Vértebras Cervicais/diagnóstico por imagem , Feminino , Análise de Elementos Finitos , Humanos
7.
J Neurosurg Pediatr ; 27(2): 218-224, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33186914

RESUMO

OBJECTIVE: Instability of the craniocervical junction (CCJ) is a well-known finding in patients with Down syndrome (DS); however, the relative contributions of bony morphology versus ligamentous laxity responsible for abnormal CCJ motion are unknown. Using finite element modeling, the authors of this study attempted to quantify those relative differences. METHODS: Two CCJ finite element models were created for age-matched pediatric patients, a patient with DS and a control without DS. Soft tissues and ligamentous structures were added based on bony landmarks from the CT scans. Ligament stiffness values were assigned using published adult ligament stiffness properties. Range of motion (ROM) testing determined that model behavior most closely matched pediatric cadaveric data when ligament stiffness values were scaled down to 25% of those found in adults. These values, along with those assigned to the other soft-tissue materials, were identical for each model to ensure that the only variable between the two was the bone morphology. The finite element models were then subjected to three types of simulations to assess ROM, anterior-posterior (AP) translation displacement, and axial tension. RESULTS: The DS model exhibited more laxity than the normal model at all levels for all of the cardinal ROMs and AP translation. For the CCJ, the flexion-extension, lateral bending, axial rotation, and AP translation values predicted by the DS model were 40.7%, 52.1%, 26.1%, and 39.8% higher, respectively, than those for the normal model. When simulating axial tension, the soft-tissue structural stiffness values predicted by the DS and normal models were nearly identical. CONCLUSIONS: The increased laxity exhibited by the DS model in the cardinal ROMs and AP translation, along with the nearly identical soft-tissue structural stiffness values exhibited in axial tension, calls into question the previously held notion that ligamentous laxity is the sole explanation for craniocervical instability in DS.


Assuntos
Articulação Atlantoccipital/diagnóstico por imagem , Vértebras Cervicais/diagnóstico por imagem , Síndrome de Down/diagnóstico por imagem , Análise de Elementos Finitos/estatística & dados numéricos , Instabilidade Articular/diagnóstico por imagem , Adulto , Pontos de Referência Anatômicos , Fenômenos Biomecânicos , Osso e Ossos/anatomia & histologia , Cadáver , Criança , Pré-Escolar , Feminino , Humanos , Ligamentos/patologia , Masculino , Modelos Estatísticos , Amplitude de Movimento Articular , Tomografia Computadorizada por Raios X
8.
J Mech Behav Biomed Mater ; 99: 118-126, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31351401

RESUMO

Elastin is a biopolymer known to provide resilience to extensible biologic tissues through elastic recoil of its highly crosslinked molecular network. Recent studies have demonstrated that elastic fibers in ligament provide significant resistance to tensile and especially shear stress. We hypothesized that the biomechanics of elastic fibers in ligament could be described as transversely isotropic with both fiber and matrix components in a multi-material mixture. Similarly, we hypothesized that material coefficients derived using the experimental tensile response could be used to predict the experimental shear response. Experimental data for uniaxial and transverse tensile testing of control tissues, and those enzymatically digested to disrupt elastin, were used as inputs to a material coefficient optimization algorithm. An additive decomposition of the strain energy was used to model the total stress as the sum of contributions from collagen fibers, elastic fibers, elastic matrix, and ground substance matrix. Matrices were modeled as isotropic Veronda-Westmann hyperelastic materials, whereas fiber families were modeled as piecewise exponential-linear hyperelastic materials. Optimizations provided excellent fits to the tensile experimental data for each treatment case and material model. Given the disparity in magnitude of stresses between longitudinal and transverse/shear tests and agreement between models and experiments, the hypothesized transversely isotropic material of elastin symmetry was supported. In addition, the coefficients derived from uniaxial and transverse tensile experiments provided reasonable predictions of the experimental behavior during shear deformation. The magnitudes of coefficients representing stress, nonlinearity, and stiffness supported the experimental evidence that elastic fibers dominate the low strain tensile and shear response of ligament. These findings demonstrate that the additive decomposition modeling strategy can represent each discrete fiber and matrix constituent and their relative contribution to the material response of the tissue. These experimental data and the validated constitutive model provide essential inputs and a framework to refine existing computational models of ligament and tendon mechanics by explicitly representing the mechanical contributions of elastic fibers.


Assuntos
Biopolímeros/química , Colágeno/química , Matriz Extracelular/química , Algoritmos , Animais , Simulação por Computador , Elasticidade , Ligamentos/fisiologia , Teste de Materiais , Resistência ao Cisalhamento , Sus scrofa , Tendões/fisiologia , Resistência à Tração
9.
J Neurosurg Spine ; : 1-9, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771758

RESUMO

OBJECTIVEThere is contradictory evidence regarding the relative contribution of the key stabilizing ligaments of the occipitoatlantal (OA) joint. Cadaveric studies are limited by the nature and the number of injury scenarios that can be tested to identify OA stabilizing ligaments. Finite element (FE) analysis can overcome these limitations and provide valuable data in this area. The authors completed an FE analysis of 5 subject-specific craniocervical junction (CCJ) models to investigate the biomechanics of the OA joint and identify the ligamentous structures essential for stability.METHODSIsolated and combined injury scenarios were simulated under physiological loads for 5 validated CCJ FE models to assess the relative role of key ligamentous structures on OA joint stability. Each model was tested in flexion-extension, axial rotation, and lateral bending in various injury scenarios. Isolated ligamentous injury scenarios consisted of either decreasing the stiffness of the OA capsular ligaments (OACLs) or completely removing the transverse ligament (TL), tectorial membrane (TM), or alar ligaments (ALs). Combination scenarios were also evaluated.RESULTSAn isolated OACL injury resulted in the largest percentage increase in all ranges of motion (ROMs) at the OA joint compared with the other isolated injuries. Flexion, extension, lateral bending, and axial rotation significantly increased by 12.4% ± 7.4%, 11.1% ± 10.3%, 83.6% ± 14.4%, and 81.9% ± 9.4%, respectively (p ≤ 0.05 for all). Among combination injuries, OACL+TM+TL injury resulted in the most consistent significant increases in ROM for both the OA joint and the CCJ during all loading scenarios. OACL+AL injury caused the most significant percentage increase for OA joint axial rotation.CONCLUSIONSThese results demonstrate that the OACLs are the key stabilizing ligamentous structures of the OA joint. Injury of these primary stabilizing ligaments is necessary to cause OA instability. Isolated injuries of TL, TM, or AL are unlikely to result in appreciable instability at the OA joint.

10.
Comput Methods Biomech Biomed Engin ; 21(6): 444-452, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30010415

RESUMO

Finite element analysis has proven to be a viable method for assessing many structure-function relationships in the human lumbar spine. Several validated models of the spine have been published, but they typically rely on commercial packages and are difficult to share between labs. The goal of this study is to present the development of the first open-access models of the human lumbar spine in FEBio. This modeling framework currently targets three deficient areas in the field of lumbar spine modeling: 1) open-access models, 2) accessibility for multiple meshing schemes, and 3) options to include advanced hyperelastic and biphasic constitutive models.


Assuntos
Análise de Elementos Finitos , Vértebras Lombares/fisiologia , Modelos Biológicos , Fenômenos Biomecânicos , Força Compressiva , Feminino , Humanos , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Fatores de Tempo , Articulação Zigapofisária/fisiologia
11.
J Biomech ; 52: 31-37, 2017 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-28041611

RESUMO

There is a mean incidence of osteoarthritis (OA) of the hip in 8% of the overall population. In the presence of focal chondral defects, defined as localized damage to the articular cartilage, there is an increased risk of symptomatic progression toward OA. This relationship between chondral defects and subsequent development of OA has led to substantial efforts to develop effective procedures for surgical cartilage repair. This study examined the effects of chondral defects and labral delamination on cartilage mechanics in the dysplastic hip during the gait cycle using subject-specific finite element analysis. Models were generated from volumetric CT data and analyzed with simulated chondral defects at the chondrolabral junction on the posterior acetabulum during five distinct points in the gait cycle. Focal chondral defects increased maximum shear stress on the osteochondral surface of the acetabular cartilage, when compared to the intact case. This effect was amplified with labral delamination. Additionally, chondral defects increased the first principal Lagrange strain on the articular surface of the acetabular cartilage and labrum. Labral delamination relieved some of this tensile strain. As defect size was increased, contact stress increased in the medial zone of the acetabulum, while it decreased anteriorly. The results suggest that in the presence of chondral defects and labral delamination the cartilage experiences elevated tensile strains and shear and contact stress, which could lead to further damage of the cartilage, and subsequent arthritic progression. The framework presented here will serve as the procedure for future finite element studies on cartilage mechanics in hips with varying disease states with simulated chondral defects and labral tears.


Assuntos
Cartilagem Articular/fisiopatologia , Luxação do Quadril/fisiopatologia , Articulação do Quadril/fisiopatologia , Modelos Biológicos , Acetábulo/fisiopatologia , Adulto , Cartilagem Articular/lesões , Feminino , Análise de Elementos Finitos , Marcha/fisiologia , Humanos , Masculino , Estresse Mecânico , Adulto Jovem
12.
J Biomech ; 49(5): 659-667, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26900037

RESUMO

Although it is easier to generate finite element discretizations with tetrahedral elements, trilinear hexahedral (HEX8) elements are more often used in simulations of articular contact mechanics. This is due to numerical shortcomings of linear tetrahedral (TET4) elements, limited availability of quadratic tetrahedron elements in combination with effective contact algorithms, and the perceived increased computational expense of quadratic finite elements. In this study we implemented both ten-node (TET10) and fifteen-node (TET15) quadratic tetrahedral elements in FEBio (www.febio.org) and compared their accuracy, robustness in terms of convergence behavior and computational cost for simulations relevant to articular contact mechanics. Suitable volume integration and surface integration rules were determined by comparing the results of several benchmark contact problems. The results demonstrated that the surface integration rule used to evaluate the contact integrals for quadratic elements affected both convergence behavior and accuracy of predicted stresses. The computational expense and robustness of both quadratic tetrahedral formulations compared favorably to the HEX8 models. Of note, the TET15 element demonstrated superior convergence behavior and lower computational cost than both the TET10 and HEX8 elements for meshes with similar numbers of degrees of freedom in the contact problems that we examined. Finally, the excellent accuracy and relative efficiency of these quadratic tetrahedral elements was illustrated by comparing their predictions with those for a HEX8 mesh for simulation of articular contact in a fully validated model of the hip. These results demonstrate that TET10 and TET15 elements provide viable alternatives to HEX8 elements for simulation of articular contact mechanics.


Assuntos
Análise de Elementos Finitos , Articulações , Fenômenos Mecânicos , Algoritmos , Fenômenos Biomecânicos , Humanos , Estresse Mecânico
13.
J Neurosurg Pediatr ; 17(4): 497-503, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26684768

RESUMO

OBJECT There is a significant deficiency in understanding the biomechanics of the pediatric craniocervical junction (CCJ) (occiput-C2), primarily because of a lack of human pediatric cadaveric tissue and the relatively small number of treated patients. To overcome this deficiency, a finite element model (FEM) of the pediatric CCJ was created using pediatric geometry and parameterized adult material properties. The model was evaluated under the physiological range of motion (ROM) for flexion-extension, axial rotation, and lateral bending and under tensile loading. METHODS This research utilizes the FEM method, which is a numerical solution technique for discretizing and analyzing systems. The FEM method has been widely used in the field of biomechanics. A CT scan of a 13-month-old female patient was used to create the 3D geometry and surfaces of the FEM model, and an open-source FEM software suite was used to apply the material properties and boundary and loading conditions and analyze the model. The published adult ligament properties were reduced to 50%, 25%, and 10% of the original stiffness in various iterations of the model, and the resulting ROMs for flexion-extension, axial rotation, and lateral bending were compared. The flexion-extension ROMs and tensile stiffness that were predicted by the model were evaluated using previously published experimental measurements from pediatric cadaveric tissues. RESULTS The model predicted a ROM within 1 standard deviation of the published pediatric ROM data for flexion-extension at 10% of adult ligament stiffness. The model's response in terms of axial tension also coincided well with published experimental tension characterization data. The model behaved relatively stiffer in extension than in flexion. The axial rotation and lateral bending results showed symmetric ROM, but there are currently no published pediatric experimental data available for comparison. The model predicts a relatively stiffer ROM in both axial rotation and lateral bending in comparison with flexion-extension. As expected, the flexion-extension, axial rotation, and lateral bending ROMs increased with the decrease in ligament stiffness. CONCLUSIONS An FEM of the pediatric CCJ was created that accurately predicts flexion-extension ROM and axial force displacement of occiput-C2 when the ligament material properties are reduced to 10% of the published adult ligament properties. This model gives a reasonable prediction of pediatric cervical spine ligament stiffness, the relationship between flexion-extension ROM, and ligament stiffness at the CCJ. The creation of this model using open-source software means that other researchers will be able to use the model as a starting point for research.


Assuntos
Articulação Atlantoccipital/anatomia & histologia , Articulação Atlantoccipital/fisiologia , Vértebras Cervicais/anatomia & histologia , Modelos Neurológicos , Osso Occipital/anatomia & histologia , Amplitude de Movimento Articular/fisiologia , Adolescente , Fenômenos Biomecânicos , Feminino , Humanos
14.
Nat Genet ; 47(5): 496-504, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25807280

RESUMO

The diaphragm is an essential mammalian skeletal muscle, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDHs), a common and often lethal birth defect. The diaphragm is derived from multiple embryonic sources, but how these give rise to the diaphragm is unknown, and, despite the identification of many CDH-associated genes, the etiology of CDH is incompletely understood. Using mouse genetics, we show that the pleuroperitoneal folds (PPFs), which are transient embryonic structures, are the source of the diaphragm's muscle connective tissue and regulate muscle development, and we show that the striking migration of PPF cells controls diaphragm morphogenesis. Furthermore, Gata4 mosaic mutations in PPF-derived muscle connective tissue fibroblasts result in the development of localized amuscular regions that are biomechanically weaker and more compliant, leading to CDH. Thus, the PPFs and muscle connective tissue are critical for diaphragm development, and mutations in PPF-derived fibroblasts are a source of CDH.


Assuntos
Diafragma/embriologia , Hérnias Diafragmáticas Congênitas/patologia , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Tecido Conjuntivo/patologia , Diafragma/patologia , Modelos Animais de Doenças , Fibroblastos/fisiologia , Fator de Transcrição GATA4/genética , Deleção de Genes , Fator de Crescimento de Hepatócito/metabolismo , Hérnias Diafragmáticas Congênitas/genética , Pulmão/diagnóstico por imagem , Pulmão/embriologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Desenvolvimento Muscular , Mioblastos/fisiologia , Microtomografia por Raio-X
15.
J Biomech ; 47(12): 3201-9, 2014 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-25134434

RESUMO

Ligaments and tendons undergo volume loss when stretched along the primary fiber axis, which is evident by the large, strain-dependent Poisson's ratios measured during quasi-static tensile tests. Continuum constitutive models that have been used to describe ligament material behavior generally assume incompressibility, which does not reflect the volumetric material behavior seen experimentally. We developed a strain energy equation that describes large, strain dependent Poisson's ratios and nonlinear, transversely isotropic behavior using a novel method to numerically enforce the desired volumetric behavior. The Cauchy stress and spatial elasticity tensors for this strain energy equation were derived and implemented in the FEBio finite element software (www.febio.org). As part of this objective, we derived the Cauchy stress and spatial elasticity tensors for a compressible transversely isotropic material, which to our knowledge have not appeared previously in the literature. Elastic simulations demonstrated that the model predicted the nonlinear, upwardly concave uniaxial stress-strain behavior while also predicting a strain-dependent Poisson's ratio. Biphasic simulations of stress relaxation predicted a large outward fluid flux and substantial relaxation of the peak stress. Thus, the results of this study demonstrate that the viscoelastic behavior of ligaments and tendons can be predicted by modeling fluid movement when combined with a large Poisson's ratio. Further, the constitutive framework provides the means for accurate simulations of ligament volumetric material behavior without the need to resort to micromechanical or homogenization methods, thus facilitating its use in large scale, whole joint models.


Assuntos
Ligamentos/fisiologia , Modelos Biológicos , Tendões/fisiologia , Animais , Fenômenos Biomecânicos , Elasticidade , Humanos , Coelhos , Estresse Mecânico
16.
Biomech Model Mechanobiol ; 13(2): 387-400, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23736783

RESUMO

Hip osteoarthritis may be initiated and advanced by abnormal cartilage contact mechanics, and finite element (FE) modeling provides an approach with the potential to allow the study of this process. Previous FE models of the human hip have been limited by single specimen validation and the use of quasi-linear or linear elastic constitutive models of articular cartilage. The effects of the latter assumptions on model predictions are unknown, partially because data for the instantaneous behavior of healthy human hip cartilage are unavailable. The aims of this study were to develop and validate a series of specimen-specific FE models, to characterize the regional instantaneous response of healthy human hip cartilage in compression, and to assess the effects of material nonlinearity, inhomogeneity and specimen-specific material coefficients on FE predictions of cartilage contact stress and contact area. Five cadaveric specimens underwent experimental loading, cartilage material characterization and specimen-specific FE modeling. Cartilage in the FE models was represented by average neo-Hookean, average Veronda Westmann and specimen- and region-specific Veronda Westmann hyperelastic constitutive models. Experimental measurements and FE predictions compared well for all three cartilage representations, which was reflected in average RMS errors in contact stress of less than 25%. The instantaneous material behavior of healthy human hip cartilage varied spatially, with stiffer acetabular cartilage than femoral cartilage and stiffer cartilage in lateral regions than in medial regions. The Veronda Westmann constitutive model with average material coefficients accurately predicted peak contact stress, average contact stress, contact area and contact patterns. The use of subject- and region-specific material coefficients did not increase the accuracy of FE model predictions. The neo-Hookean constitutive model underpredicted peak contact stress in areas of high stress. The results of this study support the use of average cartilage material coefficients in predictions of cartilage contact stress and contact area in the normal hip. The regional characterization of cartilage material behavior provides the necessary inputs for future computational studies, to investigate other mechanical parameters that may be correlated with OA and cartilage damage in the human hip. In the future, the results of this study can be applied to subject-specific models to better understand how abnormal hip contact stress and contact area contribute to OA.


Assuntos
Quadril/fisiologia , Estresse Fisiológico , Simulação por Computador , Humanos
17.
J Biomech ; 46(6): 1121-7, 2013 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-23453394

RESUMO

Quantifying cartilage contact stress is paramount to understanding hip osteoarthritis. Discrete element analysis (DEA) is a computationally efficient method to estimate cartilage contact stresses. Previous applications of DEA have underestimated cartilage stresses and yielded unrealistic contact patterns because they assumed constant cartilage thickness and/or concentric joint geometry. The study objectives were to: (1) develop a DEA model of the hip joint with subject-specific bone and cartilage geometry, (2) validate the DEA model by comparing DEA predictions to those of a validated finite element analysis (FEA) model, and (3) verify both the DEA and FEA models with a linear-elastic boundary value problem. Springs representing cartilage in the DEA model were given lengths equivalent to the sum of acetabular and femoral cartilage thickness and gap distance in the FEA model. Material properties and boundary/loading conditions were equivalent. Walking, descending, and ascending stairs were simulated. Solution times for DEA and FEA models were ~7 s and ~65 min, respectively. Irregular, complex contact patterns predicted by DEA were in excellent agreement with FEA. DEA contact areas were 7.5%, 9.7% and 3.7% less than FEA for walking, descending stairs, and ascending stairs, respectively. DEA models predicted higher peak contact stresses (9.8-13.6 MPa) and average contact stresses (3.0-3.7 MPa) than FEA (6.2-9.8 and 2.0-2.5 MPa, respectively). DEA overestimated stresses due to the absence of the Poisson's effect and a direct contact interface between cartilage layers. Nevertheless, DEA predicted realistic contact patterns when subject-specific bone geometry and cartilage thickness were used. This DEA method may have application as an alternative to FEA for pre-operative planning of joint-preserving surgery such as acetabular reorientation during peri-acetabular osteotomy.


Assuntos
Osso e Ossos/fisiologia , Cartilagem Articular/fisiologia , Articulação do Quadril/fisiologia , Modelos Biológicos , Adulto , Análise de Elementos Finitos , Humanos , Masculino , Reprodutibilidade dos Testes , Estresse Mecânico
18.
Biomech Model Mechanobiol ; 12(6): 1195-204, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23400805

RESUMO

Aligned, collagenous tissues such as tendons and ligaments are composed primarily of water and type I collagen, organized hierarchically into nanoscale fibrils, microscale fibers and mesoscale fascicles. Force transfer across scales is complex and poorly understood. Since innervation, the vasculature, damage mechanisms and mechanotransduction occur at the microscale and mesoscale, understanding multiscale interactions is of high importance. This study used a physical model in combination with a computational model to isolate and examine the mechanisms of force transfer between scales. A collagen-based surrogate served as the physical model. The surrogate consisted of extruded collagen fibers embedded within a collagen gel matrix. A micromechanical finite element model of the surrogate was validated using tensile test data that were recorded using a custom tensile testing device mounted on a confocal microscope. Results demonstrated that the experimentally measured macroscale strain was not representative of the microscale strain, which was highly inhomogeneous. The micromechanical model, in combination with a macroscopic continuum model, revealed that the microscale inhomogeneity resulted from size effects in the presence of a constrained boundary. A sensitivity study indicated that significant scale effects would be present over a range of physiologically relevant inter-fiber spacing values and matrix material properties. The results indicate that the traditional continuum assumption is not valid for describing the macroscale behavior of the surrogate and that boundary-induced size effects are present.


Assuntos
Colágeno/metabolismo , Ligamentos/metabolismo , Modelos Biológicos , Tendões/metabolismo , Animais , Fenômenos Biomecânicos , Colágenos Fibrilares/ultraestrutura , Análise de Elementos Finitos , Géis , Microscopia Confocal , Ratos , Reprodutibilidade dos Testes
19.
J Biomech Eng ; 134(1): 011005, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22482660

RESUMO

In the field of computational biomechanics, investigators have primarily used commercial software that is neither geared toward biological applications nor sufficiently flexible to follow the latest developments in the field. This lack of a tailored software environment has hampered research progress, as well as dissemination of models and results. To address these issues, we developed the FEBio software suite (http://mrl.sci.utah.edu/software/febio), a nonlinear implicit finite element (FE) framework, designed specifically for analysis in computational solid biomechanics. This paper provides an overview of the theoretical basis of FEBio and its main features. FEBio offers modeling scenarios, constitutive models, and boundary conditions, which are relevant to numerous applications in biomechanics. The open-source FEBio software is written in C++, with particular attention to scalar and parallel performance on modern computer architectures. Software verification is a large part of the development and maintenance of FEBio, and to demonstrate the general approach, the description and results of several problems from the FEBio Verification Suite are presented and compared to analytical solutions or results from other established and verified FE codes. An additional simulation is described that illustrates the application of FEBio to a research problem in biomechanics. Together with the pre- and postprocessing software PREVIEW and POSTVIEW, FEBio provides a tailored solution for research and development in computational biomechanics.


Assuntos
Análise de Elementos Finitos , Fenômenos Mecânicos , Software , Fenômenos Biomecânicos , Força Compressiva , Elasticidade , Humanos , Ligamentos , Teste de Materiais , Dinâmica não Linear , Articulação do Ombro , Estresse Mecânico , Propriedades de Superfície
20.
J Orthop Res ; 30(7): 1133-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22213112

RESUMO

Our objectives were to determine cartilage contact stress during walking, stair climbing, and descending stairs in a well-defined group of normal volunteers and to assess variations in contact stress and area among subjects and across loading scenarios. Ten volunteers without history of hip pain or disease with normal lateral center-edge angle and acetabular index were selected. Computed tomography imaging with contrast was performed on one hip. Bone and cartilage surfaces were segmented from volumetric image data, and subject-specific finite element models were constructed and analyzed using a validated protocol. Acetabular contact stress and area were determined for seven activities. Peak stress ranged from 7.52±2.11 MPa for heel-strike during walking (233% BW) to 8.66 ± 3.01 MPa for heel-strike during descending stairs (261% BW). Average contact area across all activities was 34% of the surface area of the acetabular cartilage. The distribution of contact stress was highly non-uniform, and more variability occurred among subjects for a given activity than among activities for a single subject. The magnitude and area of contact stress were consistent between activities, although inter-activity shifts in contact pattern were found as the direction of loading changed. Relatively small incongruencies between the femoral and acetabular cartilage had a large effect on the contact stresses. These effects tended to persist across all simulated activities. These results demonstrate the diversity and trends in cartilage contact stress in healthy hips during activities of daily living and provide a basis for future comparisons between normal and pathologic hips.


Assuntos
Cartilagem Articular/fisiologia , Análise de Elementos Finitos , Articulação do Quadril/fisiologia , Modelos Biológicos , Acetábulo/diagnóstico por imagem , Acetábulo/fisiologia , Atividades Cotidianas , Adulto , Fenômenos Biomecânicos/fisiologia , Cartilagem Articular/diagnóstico por imagem , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Masculino , Valor Preditivo dos Testes , Valores de Referência , Estresse Mecânico , Tomografia Computadorizada por Raios X , Suporte de Carga/fisiologia , Adulto Jovem
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