A new constitutive model for permanent deformation of blood clots with application to simulation of aspiration thrombectomy

Fereidoonnezhad, Behrooz; McGarry, Patrick

doi:10.1016/j.jbiomech.2021.110865

Cited by 11 publications

(7 citation statements)

References 32 publications

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“…Several biomechanical models of fibrin and clot networks of varying scope and scale have been developed [recently reviewed in (17)]. These include macroscopic continuum models for large deformation, viscoelastic response, and rupture of clots (18)(19)(20)(21); mesoscopic models of the network that explicitly account for the mechanics of individual fibers (22)(23)(24); and microscale, molecular models of the unfolding of single fibrin fibers (25). However, it remains underexplored how the nonlinear mechanical behavior of clots emerges from the interplay between fibrin cross-linking, platelet contractility, and network topology.…”

Section: Introductionmentioning

confidence: 99%

Clots reveal anomalous elastic behavior of fiber networks

Zakharov,

Awan,

Gopinath

et al. 2024

Sci. Adv.

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The adaptive mechanical properties of soft and fibrous biological materials are relevant to their functionality. The emergence of the macroscopic response of these materials to external stress and intrinsic cell traction from local deformations of their structural components is not well understood. Here, we investigate the nonlinear elastic behavior of blood clots by combining microscopy, rheology, and an elastic network model that incorporates the stretching, bending, and buckling of constituent fibrin fibers. By inhibiting fibrin cross-linking in blood clots, we observe an anomalous softening regime in the macroscopic shear response as well as a reduction in platelet-induced clot contractility. Our model explains these observations from two independent macroscopic measurements in a unified manner, through a single mechanical parameter, the bending stiffness of individual fibers. Supported by experimental evidence, our mechanics-based model provides a framework for predicting and comprehending the nonlinear elastic behavior of blood clots and other active biopolymer networks in general.

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Section: Introductionmentioning

confidence: 99%

Clots reveal anomalous elastic behavior of fiber networks

Zakharov,

Awan,

Gopinath

et al. 2024

Sci. Adv.

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“…clots prepared from blood mixtures of varying haematocrit) has shown that the mechanical behaviour is strongly dependent upon the clot composition with the microstructure of the clot also a function of age. A hyper-viscoelastic constitutive model is suitable to capture the mechanical behaviour, Johnson et al (2021), and this has recently been implemented in models using simplified geometries to provide accurate predictions of the clot deformed shape, Fereidoonnezhad et al (2021) and Fereidoonnezhad and McGarry (2022).…”

Section: Acute Ischaemic Strokementioning

confidence: 99%

Review of in silico models of cerebral blood flow in health and pathology

2023

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In this review, we provide a summary of the state-of-the-art in the in silico modelling of cerebral blood flow and its application in in silico clinical trials. Cerebral blood flow plays a key role in the transport of nutrients, including oxygen and glucose, to brain cells, and the cerebral vasculature is a highly complex, multi-scale, dynamic system that acts to ensure that supply and demand of these nutrients are continuously balanced. It also plays a key role in the transport of other substances, such as rt-PA, to brain tissue. Any dysfunction in cerebral blood flow can rapidly lead to cell death and permanent damage to brain regions, leading to loss of bodily functions and death.The complexity of the cerebral vasculature and the difficulty in obtaining accurate anatomical information combine to make mathematical models of cerebral blood flow key in understanding brain supply, diagnosis of cerebrovascular disease, selection of the optimum intervention, and neurosurgical planning. Similar in silico models have now been widely applied in other body organs, but models of cerebral blood flow lag far behind. The increased availability of experimental data in the last 15 years however has enabled these models to develop more rapidly and this progress is the focus of this review.We thus present a brief review of the cerebral vasculature and the mathematical foundations of cerebral blood flow. We demonstrate how such models can be applied in the context of cerebral diseases and show how this work has recently been expanded to in silico trials for the first time. Most work to date in this context has been performed for ischaemic stroke or cerebral aneurysms, but in-silico models have many other applications in neurodegenerative diseases where mathematical models have a vital role to play in testing hypotheses and providing test beds for clinical interventions.

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“…To understand the overall structure-mechanics relationships of the composite blood clot, several biomechanical models of varying scope have been developed (recently reviewed in ( 8 )). These models include constitutive or phenomenological approaches to study mechanical properties of clots as a function of clot composition ( 9 ),( 10 ); continuum models to predict the macroscopic, large deformation of clots such as for predicting viscoelastic responses and clot rupture ( 11 ),( 12 ); mesoscopic models that explicitly account for the mechanics of individual fibers as a collection of elastic elements connected to form two-dimensional (2D) or three-dimensional (3D) networks with prescribed topology ( 13 ),( 14 ),( 15 ); and microscale, molecular models of the unfolding of single fibrin fibers ( 16 ). Of relevance to the current work, mesoscopic models not only describe the elastic response of the networks under macroscopic deformation modes such as shear or uniaxial tension but also provide important insights into local fiber deformation, and long-range force transmission due to platelet-fiber interactions ( 17 ),( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Clots reveal anomalous elastic behavior of fiber networks

Zakharov

Awan

Cheng

et al. 2023

Preprint

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The mechanical properties of many soft natural and synthetic biological materials are relevant to their function. The emergence of these properties from the collective response of the structural components of the material to external stress as well as to intrinsic cell traction, remains poorly understood. Here, we examine the nonlinear elastic behavior of blood clots by combining microscopy and rheological measurements with an elastic network model that accounts for the stretching, bending, and buckling of constituent fibrin fibers. We show that the inhibition of fibrin crosslinking reduces fiber bending stiffness and introduces an atypical fiber buckling-induced softening regime at intermediate shear, before the well-characterized stiffening regime. We also show that crosslinking and platelet contraction significantly alter force propagation in the network in a strain-dependent manner. Our mechanics-based model, supported by experiments, provides a framework to understand the origins of characteristic and anomalous regimes of non-linear elastic response not only in blood clots, but also more generally in active biopolymer networks.

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A new constitutive model for permanent deformation of blood clots with application to simulation of aspiration thrombectomy

Cited by 11 publications

References 32 publications

Clots reveal anomalous elastic behavior of fiber networks

Clots reveal anomalous elastic behavior of fiber networks

Review of in silico models of cerebral blood flow in health and pathology

Clots reveal anomalous elastic behavior of fiber networks

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