1,720,973 research outputs found
Impact of Tissue Damage and Hemodynamics on Restenosis Following Percutaneous Transluminal Angioplasty: A Patient-Specific Multiscale Model.
Full text linkMultiscale agent-based modeling frameworks have recently emerged as promising mechanobiological models to capture the interplay between biomechanical forces, cellular behavior, and molecular pathways underlying restenosis following percutaneous transluminal angioplasty (PTA). However, their applications are mainly limited to idealized scenarios. Herein, a multiscale agent-based modeling framework for investigating restenosis following PTA in a patient-specific superficial femoral artery (SFA) is proposed. The framework replicates the 2-month arterial wall remodeling in response to the PTA-induced injury and altered hemodynamics, by combining three modules: (i) the PTA module, consisting in a finite element structural mechanics simulation of PTA, featuring anisotropic hyperelastic material models coupled with a damage formulation for fibrous soft tissue and the element deletion strategy, providing the arterial wall damage and post-intervention configuration, (ii) the hemodynamics module, quantifying the post-intervention hemodynamics through computational fluid dynamics simulations, and (iii) the tissue remodeling module, based on an agent-based model of cellular dynamics. Two scenarios were explored, considering balloon expansion diameters of 5.2 and 6.2 mm. The framework captured PTA-induced arterial tissue lacerations and the post-PTA arterial wall remodeling. This remodeling process involved rapid cellular migration to the PTA-damaged regions, exacerbated cell proliferation and extracellular matrix production, resulting in lumen area reduction up to 1-month follow-up. After this initial reduction, the growth stabilized, due to the resolution of the inflammatory state and changes in hemodynamics. The similarity of the obtained results to clinical observations in treated SFAs suggests the potential of the framework for capturing patient-specific mechanobiological events occurring after PTA intervention
Limitations in electrophysiological model development and validation caused by differences between simulations and experimental protocols
Full text linkModels of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations. In this work, we explore the limitations of these approaches to estimate ion channel dynamics and maximum current conductances and how they could be overcome by using multiscale simulations of experimental protocols. Four human ventricular cell models, namely ten Tusscher and Panfilov (2006), Grandi et al. (2010), O'Hara et al. (2011), and Carro et al. (2011), were used. Two problems involving scales from ion channels to tissue were investigated: 1) characterization of L-type calcium voltage-dependent inactivation ICa,L; 2) identification of major ionic conductance contributors to steady-state AP markers, including APD90, APD75, APD50, APD25, Triangulation and maximal and minimal values of V and dV/dt during the AP (Vmax, Vmin, dV/dtmax, dV/dtmin). Our results show that: 1) ICa,Linactivation characteristics differed significantly when calculated from model equations and from simulations reproducing the experimental protocols. 2) Large differences were found in the ionic currents contributors to APD25, Triangulation, Vmax, dV/dtmaxand dV/dtminbetween single cells and 1D-tissue. When proposing any new model formulation, or evaluating an existing model, consistency between simulated and experimental data should be verified considering all involved effects and scales
Electrotonic Coupling Effect on Pharmacological Cardiotoxicity Assessment in Atrial Tissue
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Why non-contact tonometry tests cannot evaluate the effects of corneal collagen cross-linking
No full textPURPOSE: To assess the feasibility of characterizing and following up the mechanical behavior of the corneal tissue after corneal cross-linking (CXL) by using a combined mechanical (in vivo indentation and in vitro uniaxial tensile tests) and morphological (immunohistochemistry) experimental protocol. METHODS: CXL (3 mW/cm2; 370 nm) for 20 minutes (total dose 3.6 J/cm2) was performed on 12 New Zealand rabbits. The mechanical behavior of the cornea was characterized in small and large strain regimens using an in vivo indentation test with a laboratory device and an in vitro uniaxial tensile test, respectively. These tests and corneal immunohistochemistry were performed before (PreCXL) and on the 7th (PostCXL-7d) and 56th days (PostCXL-56d) after CXL. The intraocular pressure and corneal thickness were measured before each test. RESULTS: For the indentation tests, significant differences were found between PreCXL and PostCXL-7d and between PostCXL-7d and PostCXL-56d, but not between PreCXL and PostCXL-56d. On average, for the small strain regimen, PostCXL-7d corneas showed the most compliant behavior, with progressive recovery of the corneal stiffiness over time. For the large strain regimen, significant differences in the maximum tangent modulus between PreCXL and PostCXL-7d and between PreCXL and PostCXL-56d were observed for the uniaxial tensile tests, with no significant differences between PostCXL-7d and PostCXL-56d. Immunohistochemistry showed a lack of cells in the anterior stroma at PostCXL-7d, but at PostCXL-56d the cell density and morphology were comparable to PreCXL. CONCLUSIONS: Indentation tests cannot characterize the changes in the corneal collagen scaffold caused by the CXL, but the uniaxial test can. However, indentation tests can assess the recovery ofkeratocyte density after CXL
Development of a patient-specific cerebral vasculature fluid-structure-interaction model
Full text linkDevelopment 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
The mechanisms of potassium loss in acute myocardial ischemia: New insights from computational simulations
Full text link: Acute myocardial ischemia induces hyperkalemia (accumulation of extracellular potassium), a major perpetrator of lethal reentrant ventricular arrhythmias. Despite considerable experimental efforts to explain this pathology in the last decades, the intimate mechanisms behind hyperkalemia remain partially unknown. In order to investigate these mechanisms, we developed a novel computational model of acute myocardial ischemia which couples a) an electrophysiologically detailed human cardiomyocyte model that incorporates modifications to account for ischemia-induced changes in transmembrane currents, with b) a model of cardiac tissue and extracellular K + transport. The resulting model is able to reproduce and explain the triphasic time course of extracellular K + concentration within the ischemic zone, with values of [K+]o close to 14 mmol/L in the central ischemic zone after 30 min. In addition, the formation of a [K+]o border zone of approximately 1.2 cm 15 min after the onset of ischemia is predicted by the model. Our results indicate that the primary rising phase of [K+]o is mainly due to the imbalance between K + efflux, that increases slightly, and K + influx, that follows a reduction of the NaK pump activity by more than 50%. The onset of the plateau phase is caused by the appearance of electrical alternans (a novel mechanism identified by the model), which cause an abrupt reduction in the K + efflux. After the plateau, the secondary rising phase of [K+]o is caused by a subsequent imbalance between the K + influx, which continues to decrease slowly, and the K + efflux, which remains almost constant. Further, the study shows that the modulation of these mechanisms by the electrotonic coupling is the main responsible for the formation of the ischemic border zone in tissue, with K + transport playing only a minor role. Finally, the results of the model indicate that the injury current established between the healthy and the altered tissue is not sufficient to depolarize non-ischemic cells within the healthy tissue
Editorial: Atrial Fibrillation: Technologies for Investigation, Monitoring and Treatment, Volume II
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Stem cell morphology controls the nuclear import of transcription factors within a bioengineered 3D niche
Full text linkLAUREA MAGISTRALENelle cellule staminali la morfologia controlla l'importo nucleare di fattori di trascrizione all'interno di una nicchia cellulare 3D ingegnerizzataSTEM CELL MORPHOLOGY CONTROLS THE NUCLEAR IMPORT OF TRANSCRIPTION FACTORS WITHIN A BIOENGINEERED 3D NICH
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