In-stent restenosis represents a major cause of failure of percutaneous coronary intervention with drug-eluting stent implantation. Computational multiscale models have recently emerged as powerful tools for investigating the mechanobiological mechanisms underlying vascular adaptation processes during in-stent restenosis. However, to date, the interplay between intervention-induced inflammation, drug delivery and drug retention has been under-investigated. Here, an original patient-specific multiscale agent-based modelling framework was developed to investigate the interplay between drug release, plaque composition and intervention-induced inflammation on in-stent restenosis following drug-eluting stent implantation. The framework integrated a finite element simulation of stent expansion, with a drug transport simulation and an agent-based model of cellular dynamics. A patient-specific coronary cross-section with heterogeneous diseased tissue was considered and rigorously analyzed through a variety of scenarios, including different plaque compositions and different inflammatory responses. The analysis revealed three significant findings: (i) calcifications substantially impeded drug transport, resulting in drug-depleted regions and reduced stent efficacy; (ii) by impacting drug transport, variations in plaque composition influenced arterial wall response, with the fully-calcific scenario showing the greatest lumen area reduction; (iii) the impact of different drug receptor saturation conditions (obtained with different plaque compositions) was particularly evident under conditions of persistent inflammatory state. This study represents a significant advancement in multiscale modelling of in-stent restenosis following drug-eluting stent implantation. The results obtained provided deeper insights into the complex interactions among patient-specific plaque composition, inflammation and drug retention, suggesting a patient-specific management of the intervention, particularly in cases of complex disease.

Endovascular thrombectomy (EVT) aims at restoring blood flow in case of acute ischemic stroke by removing the thrombus occluding a large cerebral artery. During the procedure with stent-retriever, the thrombus is captured within the device, which is then retrieved, subjecting the thrombus to several forces, potentially leading to its fragmentation. In silico studies, along with mechanical characterisation of thrombi, can enhance our understanding of the EVT, helping the development of new devices and interventional strategies. Our group previously validated a numerical approach to study EVT able to account for thrombus fragmentation. In this study, the same methodology was employed to explore the applicability of the chosen failure criterion to EVT simulations and the impact of thrombus composition on the outcome of the in silico procedure. For the first time, human clot analogues experimental data were applied to this methodology. Clot analogues of three different compositions were tested, and a material model incorporating failure was calibrated, followed by a verification analysis. Finally, the calibrated material model was used to perform EVT simulations, combining the three tested thrombus compositions with three different stent retriever models. The experimental tests confirmed a compression-tension asymmetry in the stress-strain curves, showing decreasing stiffness with increasing the red blood cell (RBC) content. Applying the resulting material models to EVT simulations demonstrated: (i) the dependency of the failure criterion on the thrombus mesh size, (ii) a greater tendency for RBC-rich thrombi to fragment, and (iii) increased difficulty in retrieving RBC-poor thrombi compared to RBC-rich thrombi.

Atherosclerotic plaque rupture in coronary arteries, an important trigger of myocardial infarction, is shown to correlate with high levels of pressure-induced mechanical stresses in plaques. Finite element (FE) analyses are commonly used for plaque stress assessment. However, the required information of heterogenous material properties of atherosclerotic coronaries remains to be scarce. In this work, we characterized the component-wise mechanical properties of atherosclerotic human coronary arteries. To achieve this, we performed ex vivo inflation tests on post-mortem human coronary arteries and developed an inverse FE modeling (iFEM) pipeline, which combined high-frequency ultrasound deformation measurements, a high-field magnetic resonance-based artery composition characterization, and a machine learning-based Bayesian optimization (BO) with uniqueness assessment. By using the developed pipeline, 10 cross-sections from five atherosclerotic human coronary arteries were analyzed, and the Yeoh material model constants of the fibrous intima and arterial wall components were determined. This work outlines the developed pipeline and provides the knowledge of non-linear, multicomponent mechanical properties of atherosclerotic human coronary arteries.