Mechano-chemo-biological Computational Models for Arteries in Health, Disease and Healing: From Tissue Remodelling to Drug-eluting Devices

Marino, Michele; Vairo, Giuseppe; Wriggers, Peter

doi:10.2174/1381612826666200728145752

Cited by 3 publications

(1 citation statement)

References 184 publications

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“…Once detected as such, there are a number of interventional ways (invasive, non-invasive or minimally invasive) to alleviate plaque in an artery. The first such invasive procedure was coronary artery bypass graft (CABG) surgery, followed by minimally invasive procedures like the implantation of bare-metal stent (BMS) and drug-eluting stent (DES) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Despite this, CABG is a procedure still used today as not every patient is eligible for minimally invasive surgery such as percutaneous transluminal coronary angioplasty (PTCA) due to highly tortuous or extensively blocked arteries.…”

Section: Introductionmentioning

confidence: 99%

An unsteady analysis of two-phase binding of drug in an asymmetric stenosed vessel

Biswas¹,

Sarifuddin²,

Mandal³

2021

Biomed. Phys. Eng. Express

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In this paper, we investigate endovascular delivery to get a step ahead of the pharmacological limitations it has due to the complexity of dealing with a patient-specific vessel through a mathematical model. We divide the domain of computation into four sub-domains: the lumen, the lumen-tissue interface, the upper tissue and the lower tissue which are extracted from an asymmetric atherosclerotic image derived by the intravascular ultrasound (IVUS) technique. The injected drug at the luminal inlet is transported with the streaming blood which is considered Newtonian. An irreversible uptake kinetics of the injected drug at the lumen-tissue interface from the luminal side to the tissue domains is assumed. Subsequently, the drug is dispersed within the tissue followed by its retention in the extracellular matrix (ECM) and by receptor-mediated binding. The Marker and Cell (MAC) method has been leveraged to get a quantitative insight into the model considered. The effect of the wall absorption parameter on the concentration of all drug forms (free as well as two-phase bound) has been thoroughly investigated, and some other important factors, such as the averaged concentration, the tissue content, the fractional effect, the concentration variance and the effectiveness of drug have been graphically analyzed to gain a clear understanding of endovascular delivery. The simulated results predict that with increasing values of the absorption parameter, the averaged concentrations of all drug forms do decrease. An early saturation of binding sites takes place for smaller values of the absorption parameter, and also rapid saturation of ECM binding sites occurs as compared to receptor binding sites. Results also predict the influence of surface roughness as well as asymmetry of the domain about the centerline on the distribution and retention of drug. A thorough sensitivity analysis has been carried out to determine the influence of some parameters involved.

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Section: Introductionmentioning

confidence: 99%

An unsteady analysis of two-phase binding of drug in an asymmetric stenosed vessel

Biswas¹,

Sarifuddin²,

Mandal³

2021

Biomed. Phys. Eng. Express

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Unraveling the complexity of vascular tone regulation: a multiscale computational approach to integrating chemo-mechano-biological pathways with cardiovascular biomechanics

Marino,

Sauty,

Vairo

2024

Biomech Model Mechanobiol

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Vascular tone regulation is a crucial aspect of cardiovascular physiology, with significant implications for overall cardiovascular health. However, the precise physiological mechanisms governing smooth muscle cell contraction and relaxation remain uncertain. The complexity of vascular tone regulation stems from its multiscale and multifactorial nature, involving global hemodynamics, local flow conditions, tissue mechanics, and biochemical pathways. Bridging this knowledge gap and translating it into clinical practice presents a challenge. In this paper, a computational model is presented to integrate chemo-mechano-biological pathways with cardiovascular biomechanics, aiming to unravel the intricacies of vascular tone regulation. The computational framework combines an algebraic description of global hemodynamics with detailed finite element analyses at the scale of vascular segments for describing their passive and active mechanical response, as well as the molecular transport problem linked with chemo-biological pathways triggered by wall shear stresses. Their coupling is accounted for by considering a two-way interaction. Specifically, the focus is on the role of nitric oxide-related molecular pathways, which play a critical role in modulating smooth muscle contraction and relaxation to maintain vascular tone. The computational framework is employed to examine the interplay between localized alterations in the biomechanical response of a specific vessel segment—such as those induced by calcifications or endothelial dysfunction–and the broader global hemodynamic conditions—both under basal and altered states. The proposed approach aims to advance our understanding of vascular tone regulation and its impact on cardiovascular health. By incorporating chemo-mechano-biological mechanisms into in silico models, this study allows us to investigate cardiovascular responses to multifactorial stimuli and incorporate the role of adaptive homeostasis in computational biomechanics frameworks.

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Unsteady transport and two-phase binding of a drug in an atherosclerotic artery

Biswas

Sarifuddin²,

Mandal

2022

Physics of Fluids

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To quantify the biology and physical understanding of endovascular drug delivery, a mathematical model that accounts for the two-phase binding of drug molecules in a diseased patient-specific artery has been developed. Using an image segmentation technique, the edges of the computational domain have been successfully extracted from an asymmetric intravascular ultrasound longitudinal image. The flow inside the porous tissue is described by the Brinkman model, and the luminal flow is Newtonian. At the lumen–tissue interface, an irreversible uptake kinetics for the injected drug from the luminal side into the tissue is taken into account. Furthermore, the drug's two-phase binding process, namely, the nonspecific binding caused by the drug's trapping in the extracellular medium (ECM-bound) and the specific binding caused by the interaction between drug molecules and receptors (REC-bound), has been considered. The Marker and Cell method has been leveraged to solve the governing equations numerically. Spatiotemporal variations of free drug, ECM-bound drug, and REC-bound drug are examined thoroughly for varying absorption parameter. Simulated results reveal that the interstitial flow amplifies drug distribution, retention, and delivery effectiveness, but flow separation downstream of the constriction reduces transmural flux. Concomitantly, the larger the absorption parameter, the higher the tissue content and effectiveness; nevertheless, significantly, larger absorption parameter values do not necessarily suggest improved delivery effectiveness. A thorough sensitivity analysis was carried out to predict the effects of some of the parameters involved.

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Mechano-chemo-biological Computational Models for Arteries in Health, Disease and Healing: From Tissue Remodelling to Drug-eluting Devices

Cited by 3 publications

References 184 publications

An unsteady analysis of two-phase binding of drug in an asymmetric stenosed vessel

An unsteady analysis of two-phase binding of drug in an asymmetric stenosed vessel

Unraveling the complexity of vascular tone regulation: a multiscale computational approach to integrating chemo-mechano-biological pathways with cardiovascular biomechanics

Unsteady transport and two-phase binding of a drug in an atherosclerotic artery

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