Impact of hypertension and arterial wall expansion on transport properties and atherosclerosis progression.

This study explored the impact of hypertension on atheroma plaque formation through a mechanobiological model. The model incorporates blood flow via the Navier-Stokes equation. Plasma flow through the endothelium is determined by Darcy's law and the Kedem-Katchalsky equations, which consider the three-pore model utilized for substance flow across the endothelium. The behaviour of these substances within the arterial wall is described by convection-diffusion-reaction equations, while the arterial wall itself is modelled as a hyperelastic material using Yeoh's model. To accurately evaluate hypertension's influence, adjustments were made to incorporate wall compression-induced wall compaction by radial compression. This compaction impacts three key variables of the transport phenomena: diffusion, porosity, and permeability. Based on the obtained findings, we can conclude that hypertension significantly augments plaque growth, leading to an over 400% increase in plaque thickness. This effect persists regardless of whether wall mechanics are considered. Tortuosity, arterial wall permeability, and porosity have minimal impact on atheroma plaque growth under normal arterial pressure. However, the atheroma plaque growth changes dramatically in hypertensive cases. In such scenarios, the collective influence of all factors-tortuosity, permeability, and porosity-results in nearly a 20% increase in plaque growth. This emphasizes the importance of considering wall compression due to hypertension in patient studies, where elevated blood pressure and high cholesterol levels commonly coexist.

A comprehensive experimental analysis of the local passive response across the healthy porcine left ventricle.

This work provides a comprehensive characterization of porcine myocardial tissue, combining true biaxial (TBx), simple triaxial shear (STS) and confined compression (CC) tests to analyze its elastic behavior under cyclic loads. We expanded this study to different zones of the ventricular free wall, providing insights into the local behavior along the longitudinal and radial coordinates. The aging impact was also assessed by comparing two age groups (4 and 8 months). Resulting data showed that the myocardium exhibits a highly nonlinear hyperelastic and incompressible behavior. We observed an anisotropy ratio of 2-2.4 between averaged peak stresses in TBx tests and 1-0.59-0.40 orthotropy ratios for normalised fiber-sheet-normal peak stresses in STS tests. We obtained a highly incompressible response, reaching volumetric pressures of 2-7 MPa for perfused tissue in CC tests, with notable differences when fluid drainage was allowed, suggesting a high permeability. Regional analysis showed reduced stiffness and anisotropy (20-25%) at the apical region compared to the medial, which we attributed to differences in the fiber field dispersion. Compressibility also increased towards the epicardium and apical regions. Regarding age-related variations, 8-month animals showed stiffer response (at least 25% increase), particularly in directions where the mechanical stress is absorbed by collagenous fibers (more than 90%), as supported by a histological analysis. Although compressibility of perfused tissue remained unchanged, permeability significantly reduced in 8-month-old animals. Our findings offer new insights into myocardial properties, emphasizing on local variations, which can help to get a more realistic understanding of cardiac mechanics in this common animal model. STATEMENT OF SIGNIFICANCE: In this work, we conducted a comprehensive analysis of the passive mechanical behavior of porcine myocardial tissue through biaxial, triaxial shear, and confined compression tests. Unlike previous research, we investigated the variation in mechanical response across the left ventricular free wall, conventionally assumed homogeneous, revealing differences in terms of stiffness and compressibility. Additionally, we evaluated age-related effects on mechanical properties by comparing two age groups, observing significant variations in stiffness and permeability. To date, there has been no such in-depth exploration of myocardial elastic response and compressibility considering regional variations along the wall and may contribute to a better understanding of the cardiac tissue's passive mechanical response.

Impact of geometric and hemodynamic changes on a mechanobiological model of atherosclerosis.

BACKGROUND AND OBJECTIVE: In this work, the analysis of the importance of hemodynamic updates on a mechanobiological model of atheroma plaque formation is proposed. METHODS: For that, we use an idealized and axisymmetric model of carotid artery. In addition, the behavior of endothelial cells depending on hemodynamical changes is analyzed too. A total of three computational simulations are carried out and their results are compared: an uncoupled model and two models that consider the opposite behavior of endothelial cells caused by hemodynamic changes. The model considers transient blood flow using the Navier-Stokes equation. Plasma flow across the endothelium is determined with Darcy's law and the Kedem-Katchalsky equations, considering the three-pore model, which is also employed for the flow of substances across the endothelium. The behavior of the considered substances in the arterial wall is modeled with convection-diffusion-reaction equations, and the arterial wall is modeled as a hyperelastic Yeoh's material. RESULTS: Significant variations are noted in both the morphology and stenosis ratio of the plaques when comparing the uncoupled model to the two models incorporating updates for geometry and hemodynamic stimuli. Besides, the phenomenon of double-stenosis is naturally reproduced in the models that consider both geometric and hemodynamical changes due to plaque growth, whereas it cannot be predicted in the uncoupled model. CONCLUSIONS: The findings indicate that integrating the plaque growth model with geometric and hemodynamic settings is essential in determining the ultimate shape and dimensions of the carotid plaque.

Chlorin e6-Conjugated Mesoporous Titania Nanorods as Potential Nanoplatform for Photo-Chemotherapy.

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption-desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m-2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.

Characterizing atherosclerotic tissues: in silico analysis of mechanical properties using intravascular ultrasound and inverse finite element methods.

Atherosclerosis is a prevalent cause of acute coronary syndromes that consists of lipid deposition inside the artery wall, creating an atherosclerotic plaque. Early detection may prevent the risk of plaque rupture. Nowadays, intravascular ultrasound (IVUS) is the most common medical imaging technology for atherosclerotic plaque detection. It provides an image of the section of the coronary wall and, in combination with new techniques, can estimate the displacement or strain fields. From these magnitudes and by inverse analysis, it is possible to estimate the mechanical properties of the plaque tissues and their stress distribution. In this paper, we presented a methodology based on two approaches to characterize the mechanical properties of atherosclerotic tissues. The first approach estimated the linear behavior under particular pressure. In contrast, the second technique yielded the non-linear hyperelastic material curves for the fibrotic tissues across the complete physiological pressure range. To establish and validate this method, the theoretical framework employed in silico models to simulate atherosclerotic plaques and their IVUS data. We analyzed different materials and real geometries with finite element (FE) models. After the segmentation of the fibrotic, calcification, and lipid tissues, an inverse FE analysis was performed to estimate the mechanical response of the tissues. Both approaches employed an optimization process to obtain the mechanical properties by minimizing the error between the radial strains obtained from the simulated IVUS and those achieved in each iteration. The second methodology was successfully applied to five distinct real geometries and four different fibrotic tissues, getting median R 2 of 0.97 and 0.92, respectively, when comparing the real and estimated behavior curves. In addition, the last technique reduced errors in the estimated plaque strain field by more than 20% during the optimization process, compared to the former approach. The findings enabled the estimation of the stress field over the hyperelastic plaque tissues, providing valuable insights into its risk of rupture.

A Cardiovascular Risk Optimization Program in People With Schizophrenia: A Pilot Randomized Controlled Clinical Trial.

BACKGROUND: Cardiovascular disease is one of the leading causes of premature death in people with schizophrenia. Some modifiable factors that have been implicated include unhealthy lifestyle, medication side effects, and physical comorbidities. The goal of this study was to assess the efficacy of a 6-month, multifactorial cardiovascular risk intervention to reduce cardiovascular risk (CVR) in people with schizophrenia. METHODS: We conducted a 2-arm, parallel, randomized clinical trial in a regional mental health center. Participants with at least 1 poorly controlled cardiovascular risk factor (CVRF) (hypertension, diabetes mellitus, hypercholesterolemia, or tobacco smoking) were randomly assigned to the intervention group or to a control group. The subjects in the intervention group received a patient-centered approach that included promoting a healthy lifestyle, pharmacological management of CVRFs, psychotropic drug optimization, and motivational follow-up [Programa d'optimització del RISc CArdiovascular (PRISCA)]. The main outcome was change in CVR as assessed using the Framingham-REGICOR function, after 6 months compared with the baseline in both groups. RESULTS: Forty-six participants were randomly assigned to the PRISCA group (n=23) or the control group (n=23). The most prevalent CVRFs at baseline were hypercholesterolemia (84.8%) and tobacco smoking (39.1%). The PRISCA group showed a significant reduction in the REGICOR score (-0.96%; 95% CI: -1.60 to -0.32, P=0.011) after 6 months (relative risk reduction of 20.9%), with no significant changes in the control group (0.21%; 95% CI: -0.47 to 0.89, P=0.706). In the PRISCA group, low-density lipoprotein cholesterol also decreased significantly (-27.14 mg/dL; 95% CI: -46.28 to -8.00, P=0.008). CONCLUSION: A patient-centered, multifactorial cardiovascular risk intervention improved CVR in people with schizophrenia after 6 months, which was achieved mainly by improving the lipid profile.

A Multimodal Scaffold for SDF1 Delivery Improves Cardiac Function in a Rat Subacute Myocardial Infarct Model.

Ischemic heart disease is one of the leading causes of death worldwide. The efficient delivery of therapeutic growth factors could counteract the adverse prognosis of post-myocardial infarction (post-MI). In this study, a collagen hydrogel that is able to load and appropriately deliver pro-angiogenic stromal cell-derived factor 1 (SDF1) was physically coupled with a compact collagen membrane in order to provide the suture strength required for surgical implantation. This bilayer collagen-on-collagen scaffold (bCS) showed the suitable physicochemical properties that are needed for efficient implantation, and the scaffold was able to deliver therapeutic growth factors after MI. In vitro collagen matrix biodegradation led to a sustained SDF1 release and a lack of cytotoxicity in the relevant cell cultures. In vivo intervention in a rat subacute MI model resulted in the full integration of the scaffold into the heart after implantation and biocompatibility with the tissue, with a prevalence of anti-inflammatory and pro-angiogenic macrophages, as well as evidence of revascularization and improved cardiac function after 60 days. Moreover, the beneficial effect of the released SDF1 on heart remodeling was confirmed by a significant reduction in cardiac tissue stiffness. Our findings demonstrate that this multimodal scaffold is a desirable matrix that can be used as a drug delivery system and a scaffolding material to promote functional recovery after MI.

Modeling fatigue failure in soft tissue using a visco-hyperelastic model with discontinuous damage.

Soft tissue is susceptible to injury from single high-magnitude static loads and from repetitive low-magnitude fatigue loads. While many constitutive formulations have been developed and validated to model static failure in soft tissue, a modeling framework is not well-established for fatigue failure. Here we determined the feasibility of using a visco-hyperelastic damage model with discontinuous damage (strain energy-based damage criterion) to simulate low- and high-cycle fatigue failure in soft fibrous tissue. Cyclic creep data from six uniaxial tensile fatigue experiments of human medial meniscus were used to calibrate the specimen-specific material parameters. The model was able to successfully simulate all three characteristic stages of cyclic creep, and predict the number of cycles until tissue rupture. Mathematically, damage propagated under constant cyclic stress due to time-dependent viscoelastic increases in tensile stretch that in turn increased strain energy. Our results implicate solid viscoelasticity as a fundamental regulator of fatigue failure in soft tissue, where tissue with slow stress relaxation times will be more resistant to fatigue injury. In a validation study, the visco-hyperelastic damage model was able to simulate characteristic stress-strain curves of pull to failure experiments (static failure) when using material parameters curve fit to the fatigue experiments. For the first time, we've shown that a visco-hyperelastic discontinuous damage framework can model cyclic creep and predict material rupture in soft tissue, and may enable the reliable simulation of both fatigue and static failure behavior from a single constitutive formulation.

Coronary artery properties in atherosclerosis: A deep learning predictive model.

In this work an Artificial Neural Network (ANN) was developed to help in the diagnosis of plaque vulnerability by predicting the Young modulus of the core (E core ) and the plaque (E plaque ) of atherosclerotic coronary arteries. A representative in silico database was constructed to train the ANN using Finite Element simulations covering the ranges of mechanical properties present in the bibliography. A statistical analysis to pre-process the data and determine the most influential variables was performed to select the inputs of the ANN. The ANN was based on Multilayer Perceptron architecture and trained using the developed database, resulting in a Mean Squared Error (MSE) in the loss function under 10-7, enabling accurate predictions on the test dataset for E core and E plaque . Finally, the ANN was applied to estimate the mechanical properties of 10,000 realistic plaques, resulting in relative errors lower than 3%.

Is location a significant parameter in the layer dependent dissection properties of the aorta?

Proper characterisation of biological tissue is key to understanding the effect of the biomechanical environment in the physiology and pathology of the cardiovascular system. Aortic dissection in particular is a prevalent and sometimes fatal disease that still lacks a complete comprehension of its progression. Its development and outcome, however, depend on the location in the vessel. Dissection properties of arteries are frequently studied via delamination tests, such as the T-peel test and the mixed-mode peel test. So far, a study that performs both tests throughout different locations of the aorta, as well as dissecting several interfaces, is missing. This makes it difficult to extract conclusions in terms of vessel heterogeneity, as a standardised experimental procedure cannot be assured for different studies in literature. Therefore, both dissection tests have been here performed on healthy porcine aortas, dissecting three interfaces of the vessels, i.e., the intima-media, the media-adventitia and the media within itself, considering different locations of the aorta, the ascending thoracic aorta (ATA), the descending thoracic aorta and the infrarenal abdominal aorta (IAA). Significant differences were found for both, layers and location. In particular, dissection forces in the ATA were the highest and the separation of the intima-media interface required significantly the lowest force. Moreover, dissection in the longitudinal direction of the vessel generally required more force than in the circumferential one. These results emphasise the need to characterise aortic tissue considering the specific location and dissected layer of the vessel.

Fabrication of human myocardium using multidimensional modelling of engineered tissues.

Biofabrication of human tissues has seen a meteoric growth triggered by recent technical advancements such as human induced pluripotent stem cells (hiPSCs) and additive manufacturing. However, generation of cardiac tissue is still hampered by lack of adequate mechanical properties and crucially by the often unpredictable post-fabrication evolution of biological components. In this study we employ melt electrowriting (MEW) and hiPSC-derived cardiac cells to generate fibre-reinforced human cardiac minitissues. These are thoroughly characterized in order to build computational models and simulations able to predict their post-fabrication evolution. Our results show that MEW-based human minitissues display advanced maturation 28 post-generation, with a significant increase in the expression of cardiac genes such as MYL2, GJA5, SCN5A and the MYH7/MYH6 and MYL2/MYL7 ratios. Human iPSC-cardiomyocytes are significantly more aligned within the MEW-based 3D tissues, as compared to conventional 2D controls, and also display greater expression of C×43. These are also correlated with a more mature functionality in the form of faster conduction velocity. We used these data to develop simulations capable of accurately reproducing the experimental performance. In-depth gauging of the structural disposition (cellular alignment) and intercellular connectivity (C×43) allowed us to develop an improved computational model able to predict the relationship between cardiac cell alignment and functional performance. This study lays down the path for advancing in the development ofin silicotools to predict cardiac biofabricated tissue evolution after generation, and maps the route towards more accurate and biomimetic tissue manufacture.

Mathematical modelling of endovascular drug delivery: Balloons versus stents.

The most common treatment for obstructive coronary artery disease (CAD) is the implantation of a permanent drug-eluting stent (DES). Not only has this permanency been associated with delayed healing of the artery, but it also poses challenges when treating subsequent re-narrowing due to in-stent restenosis (ISR). Drug-coated balloons (DCBs) provide a potential solution to each of these issues. While their use has been primarily limited to treating ISR, in recent years, DCBs have emerged as an attractive potential alternative to DESs for the treatment of certain de novo lesions. However, there remain a number of concerns related to the safety and efficacy of these devices. Firstly, unlike DESs, DCBs necessitate a very short drug delivery window, favouring a higher drug loading. Secondly, while the majority of coronary DCBs in Europe are coated with paclitaxel, the potential mortality signal raised with paclitaxel DCBs in peripheral interventions has shifted efforts towards the development of limus-eluting balloons. The purpose of this paper is to provide a computational model that allows drug delivery from DCBs and DESs to be investigated and compared. We present a comprehensive computational framework that employs a 2D-axisymmetric geometry, incorporates two nonlinear phases of drug binding (specific and non-specific) and includes the influence of diffusion and advection, within a multilayer arterial wall. We utilise this framework to (i) simulate drug delivery from different types of balloon platform; (ii) explore the influence of DCB application time; (iii) elucidate the importance on release kinetics of elevated pressure during DCB application; (iv) compare DCB delivery of two different drugs (sirolimus and paclitaxel) and; (v) compare simulations of DESs versus DCBs. Key measures of comparison are related to safety (drug content in tissue, DC) and efficacy (specific binding site saturation, %SBSS) markers. Our results highlight the pros and cons of each device in terms of DC and %SBSS levels achieved and, moreover, indicate the potential for designing a DCB that gives rise to sufficiently similar safety and efficacy indicators as current commercial DESs.

Self-adhesive hydrogel meshes reduce tissue incorporation and mechanical behavior versus microgrips self-fixation: a preclinical study.

PURPOSE: Atraumatic mesh fixation for abdominal hernia repair has been developed to avoid the disadvantages of classical fixation with sutures, which is considered a cause of chronic pain and discomfort. This study was designed to analyze, in the short and medium term, the biological and mechanical behavior of two self-fixing meshes compared to that of a polypropylene (PP) mesh fixed with a cyanoacrylate (CA) tissue adhesive. METHODS: Partial abdominal wall defects (6 × 4 cm) were created in New Zealand rabbits (n = 36) and repaired using a self-adhesive hydrogel mesh (Adhesix™), a self-gripping mesh (ProGrip™) or a PP mesh fixed with CA (Surgipro™ CA). After 14 and 90 days, the host tissue incorporation, macrophage response and biomechanical strength were examined. RESULTS: At 14 and 90 days, the ProGrip and Surgipro CA meshes showed good host tissue incorporation; however, the Adhesix implants presented poor integration, seroma formation and a higher degree of shrinkage. The Adhesix hydrogel was completely reabsorbed at 14 days, whereas ProGrip microhooks were observed at all study times. The macrophage response was higher in the ProGrip and Surgipro CA groups at 14 and 90 days, respectively, and decreased over time. At 90 days, the ProGrip implants showed the highest tensile strength values and the Adhesix implants showed the highest failure stretch. CONCLUSION: Meshes with mechanical microgrip self-fixation (ProGrip) show better biological and mechanical behavior than those with adhesive hydrogel (Adhesix) in a preclinical model of abdominal hernia repair in rabbits.

Biomechanical characterization and constitutive modeling of the layer-dissected residual strains and mechanical properties of abdominal porcine aorta.

We analyze the residual stresses and mechanical properties of layer-dissected infrarenal abdominal aorta (IAA). We measured the axial pre-stretch and opening angle and performed uniaxial tests to study and compare the mechanical behavior of both intact and layer-dissected porcine IAA samples under physiological loads. Finally, some of the most popular anisotropic hyperelastic constitutive models (GOH and microfiber models) were proposed to estimate the mechanical properties of the abdominal aorta by least-square fitting of the recorded in-vitro uniaxial test results. The results show that the residual stresses are layer dependent. In all cases, we found that the OA in the media layer is lower than in the whole artery, the intima and the adventitia. For the axial pre-stretch, we found that the adventitia and the media were slightly stretched in the environment of the intact arterial strip, whereas the intima appears to be compressed. Regarding the mechanical properties, the media seems to be the softest layer over the whole deformation domain showing high anisotropy, while the intima and adventitia exhibit considerable stiffness and a lower anisotropy response. Finally, all the hyperelastic anisotropic models considered in this study provided a reasonable approximation of the experimental data. The GOH model showed the best fitting.

Effects of the Haemodynamic Stimulus on the Location of Carotid Plaques Based on a Patient-Specific Mechanobiological Plaque Atheroma Formation Model.

In this work, we propose a mechanobiological atheroma growth model modulated by a new haemodynamic stimulus. To test this model, we analyse the development of atheroma plaques in patient-specific bifurcations of carotid arteries for a total time of 30 years. In particular, eight geometries (left or right carotid arteries) were segmented from clinical images and compared with the solutions obtained computationally to validate the model. The influence of some haemodynamical stimuli on the location and size of plaques is also studied. Plaques predicted by the mechanobiological models using the time average wall shear stress (TAWSS), the oscillatory shear index (OSI) and a new index proposed in this work are compared. The new index predicts the shape index of the endothelial cells as a combination of TAWSS and OSI values and was fitted using data from the literature. The mechanobiological model represents an evolution of the one previously proposed by the authors. This model uses Navier-Stokes equations to simulate blood flow along the lumen in the transient mode. It also employs Darcy's law and Kedem-Katchalsky equations for plasma and substance flow across the endothelium using the three-pore model. The mass balances of all the substances that have been considered in the model are implemented by convection-diffusion-reaction equations, and finally the growth of the plaques has been computed. The results show that by using the new mechanical stimulus proposed in this study, prediction of plaques is, in most cases, better than only using TAWSS or OSI with a minimal and maximal errors on stenosis ratio of 2.77 and 32.89 %, respectively. However, there are a few geometries in which haemodynamics cannot predict the location of plaques, and other biological or genetic factors would be more relevant than haemodynamics. In particular, the model predicts correctly eleven of the fourteen plaques presented in all the geometries considered. Additionally, a healthy geometry has been computed to check that plaque is not developed with the model in this case.

Influence of vessel curvature and plaque composition on drug transport in the arterial wall following drug-eluting stent implantation.

In the last decade, many computational models have been developed to describe the transport of drug eluted from stents and the subsequent uptake into arterial tissue. Each of these models has its own set of limitations: for example, models typically employ simplified stent and arterial geometries, some models assume a homogeneous arterial wall, and others neglect the influence of blood flow and plasma filtration on the drug transport process. In this study, we focus on two common limitations. Specifically, we provide a comprehensive investigation of the influence of arterial curvature and plaque composition on drug transport in the arterial wall following drug-eluting stent implantation. The arterial wall is considered as a three-layered structure including the subendothelial space, the media and the adventitia, with porous membranes separating them (endothelium, internal and external elastic lamina). Blood flow is modelled by the Navier-Stokes equations, while Darcy's law is used to calculate plasma filtration through the porous layers. Our findings demonstrate that arterial curvature and plaque composition have important influences on the spatiotemporal distribution of drug, with potential implications in terms of effectiveness of the treatment. Since the majority of computational models tend to neglect these features, these models are likely to be under- or over-estimating drug uptake and redistribution in arterial tissue.

Unraveling the multilayer mechanical response of aorta using layer-specific residual stresses and experimental properties.

To test the capability of the multilayer model, we used previously published layer-specific experimental data relating to the axial pre-stretch, the opening angle, the fiber distribution obtained by polarized light microscopy measurements, and the uniaxial and biaxial response of the porcine descending and abdominal aorta. We fitted the mechanical behavior of each arterial layer using Gasser, Holzapfel and Ogden strain energy function using the dispersion parameter κ as phenomenological parameter obtained during the fitting procedure or computed from the experimental fiber distribution. A multilayer finite element model of the whole aorta with the dimensions of the circumferential and longitudinal strips were then built using layer-specific material parameters previously fitted. This model was used to capture the whole aorta response under uniaxial and biaxial stress states and to reproduce the response of the whole aorta to internal pressure. Our results show that a model based on a multilayer structure without residual stresses is unable to render the uniaxial and biaxial mechanical response of the aorta (R2=0.6954 and R2=0.8582 for descending thoracic aorta (DTA) and infrarenal abdominal aorta (IAA), respectively). Only an appropriate multilayer model that includes layer-specific residual stresses can reproduce the response of the whole aorta (R2=0.9787 and R2=0.9636 for DTA and IAA respectively). In addition, a multilayer model without residual stresses produces the same stress distribution as a monolayer model without residual stresses where the maximal value of circumferential and longitudinal stresses appears at the inner radius of the intima. Finally, if layer-specific residual stresses are not available, there is less error the stress distribution using a monolayer model with residual stresses that a multilayer model without residual stresses.

How does stent expansion alter drug transport properties of the arterial wall?

Stents have become the most successful device to treat advanced atherosclerotic lesions. However, one of the main issues with these interventions is the development of restenosis. The coating of stents with antiproliferative substances to reduce this effect is now standard, although such drugs can also delay re-endothelialization of the intima. The drug release strategy is therefore a key determinant of drug-eluting stent efficacy. Many mathematical models describing drug transport in arteries have been developed and, usually separately, models describing the mechanics of arterial tissue have been devised. However, the literature is lacking a comprehensive model that adequately takes into account both the mechanical deformation of the porous arterial wall and the resulting impact on drug transport properties. In this paper, we provide the most comprehensive study to date of the effect of stent mechanical expansion on the drug transport properties of a three-layer arterial wall. Our model incorporates the state-of-the art description of the mechanical properties of arterial tissue though an anisotropic, hyperelastic material model and includes a nonlinear saturable binding model to describe drug transport in the arterial wall. We establish relationships between mechanical force generated through device expansion and alteration in diffusion within the arterial wall and perform simulations to elucidate the impact of such alterations in spatio-temporal drug release and tissue uptake. Mechanical deformation of the arterial wall results in modified drug transport properties and tissue drug concentrations, highlighting the importance of coupling solid mechanics with drug transport.