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1.
PLoS Comput Biol ; 18(10): e1010153, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36279309

RESUMO

Early lung cancer lesions develop within a unique microenvironment that undergoes constant cyclic stretch from respiration. While tumor stiffening is an established driver of tumor progression, the contribution of stress and strain to lung cancer is unknown. We developed tissue scale finite element models of lung tissue to test how early lesions alter respiration-induced strain. We found that an early tumor, represented as alveolar filling, amplified the strain experienced in the adjacent alveolar walls. Tumor stiffening further increased the amplitude of the strain in the adjacent alveolar walls and extended the strain amplification deeper into the normal lung. In contrast, the strain experienced in the tumor proper was less than the applied strain, although regions of amplification appeared at the tumor edge. Measurements of the alveolar wall thickness in clinical and mouse model samples of lung adenocarcinoma (LUAD) showed wall thickening adjacent to the tumors, consistent with cellular response to strain. Modeling alveolar wall thickening by encircling the tumor with thickened walls moved the strain amplification radially outward, to the next adjacent alveolus. Simulating iterative thickening in response to amplified strain produced tracks of thickened walls. We observed such tracks in early-stage clinical samples. The tracks were populated with invading tumor cells, suggesting that strain amplification in very early lung lesions could guide pro-invasive remodeling of the tumor microenvironment. The simulation results and tumor measurements suggest that cells at the edge of a lung tumor and in surrounding alveolar walls experience increased strain during respiration that could promote tumor progression.


Assuntos
Neoplasias Pulmonares , Alvéolos Pulmonares , Camundongos , Animais , Análise de Elementos Finitos , Alvéolos Pulmonares/patologia , Alvéolos Pulmonares/fisiologia , Pulmão , Neoplasias Pulmonares/patologia , Carcinogênese , Microambiente Tumoral
2.
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
3.
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.

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