Hybrid Microfluidic Device for High Throughput Isolation of Cells Using Aptamer Functionalized Diatom Frustules.

Circulating tumor cells (CTCs), secreted from primary and metastatic malignancies, hold a wealth of essential diagnostic and prognostic data for multiple cancers. Significantly, the information contained within these cells may hold the key to understanding cancer metastasis, both individually and fundamentally. Accordingly, developing ways to identify, isolate and interrogate CTCs plays an essential role in modern cancer research. Unfortunately, CTCs are typically present in the blood in vanishingly low titers and mixed with other blood components, making their isolation and analysis extremely challenging. Herein, we report the design, fabrication and optimization of a microfluidic device capable of automatically isolating CTCs from whole blood. This is achieved in two steps, via the passive viscoelastic separation of CTCs and white blood cells (WBCs) from red blood cells (RBCs), and subsequent active magnetophoretic separation of CTCs from WBCs. We detail the specific geometries required to balance the elastic and inertial forces required for successful passive separation of RBCs, and the use of computational fluid dynamics (CFD) to optimize active magnetophoretic separation. We subsequently describe the use of magnetic biosilica frustules, extracted from Chaetoceros sp. diatoms, to fluorescently tag CTCs and facilitate magnetic isolation. Finally, we use our microfluidic platform to separate HepG2-derived CTCs from whole blood, demonstrating exceptional CTC recovery (94.6%) and purity (89.7%).

Correction: Real-time, smartphone-based processing of lateral flow assays for early failure detection and rapid testing workflows.

[This corrects the article DOI: 10.1039/D2SD00197G.].

Modelling lower-limb peripheral arterial disease using clinically available datasets: impact of inflow boundary conditions on hemodynamic indices for restenosis prediction.

BACKGROUND AND OBJECTIVES: The integration of hemodynamic markers as risk factors in restenosis prediction models for lower-limb peripheral arteries is hindered by fragmented clinical datasets. Computed tomography (CT) scans enable vessel geometry reconstruction and can be obtained at different times than the Doppler ultrasound (DUS) images, which provide information on blood flow velocity. Computational fluid dynamics (CFD) simulations allow the computation of near-wall hemodynamic indices, whose accuracy depends on the prescribed inlet boundary condition (BC), derived from the DUS images. This study aims to: (i) investigate the impact of different DUS-derived velocity waveforms on CFD results; (ii) test whether the same vessel areas, subjected to altered hemodynamics, can be detected independently of the applied inlet BC; (iii) suggest suitable DUS images to obtain reliable CFD results. METHODS: CFD simulations were conducted on three patients treated with bypass surgery, using patient-specific DUS-derived inlet BCs recorded at either the same or different time points than the CT scan. The impact of the chosen inflow condition on bypass hemodynamics was assessed in terms of wall shear stress (WSS)-derived quantities. Patient-specific critical thresholds for the hemodynamic indices were applied to identify critical luminal areas and compare the results with a reference obtained with a DUS image acquired in close temporal proximity to the CT scan. RESULTS: The main findings indicate that: (i) DUS-derived inlet velocity waveforms acquired at different time points than the CT scan led to statistically significantly different CFD results (p<0.001); (ii) the same luminal surface areas, exposed to low time-averaged WSS, could be identified independently of the applied inlet BCs; (iii) similar outcomes were observed for the other hemodynamic indices if the prescribed inlet velocity waveform had the same shape and comparable systolic acceleration time to the one recorded in close temporal proximity to the CT scan. CONCLUSIONS: Despite a lack of standardised data collection for diseased lower-limb peripheral arteries, an accurate estimation of luminal areas subjected to altered near-wall hemodynamics is possible independently of the applied inlet BC. This holds if the applied inlet waveform shares some characteristics - derivable from the DUS report - as one matching the acquisition time of the CT scan.

Integrative modeling of hemodynamic changes and perfusion impairment in coronary microvascular disease.

Introduction: Coronary microvascular disease is one of the responsible factors for cardiac perfusion impairment. Due to diagnostic and treatment challenges, this pathology (characterized by alterations to microvasculature local hemodynamics) represents a significant yet unsolved clinical problem. Methods: Due to the poor understanding of the onset and progression of this disease, we propose a new and noninvasive strategy to quantify in-vivo hemodynamic changes occurring in the microvasculature. Specifically, we here present a conceptual workflow that combines both in-vitro and in-silico modelling for the analysis of the hemodynamic alterations in the microvasculature. Results: First, we demonstrate a hybrid additive manufacturing process to fabricate circular cross-section, biocompatible fluidic networks in polytetrafluoroethylene. We then use these microfluidic devices and computational fluid dynamics to simulate different degrees of perfusion impairment. Discussion: Ultimately, we show that the developed workflow defines a robust platform for the multiscale analysis of multifactorial events occurring in coronary microvascular disease.

Real-time, smartphone-based processing of lateral flow assays for early failure detection and rapid testing workflows.

Despite their simplicity, lateral flow immunoassays (LFIAs) remain a crucial weapon in the diagnostic arsenal, particularly at the point-of-need. However, methods for analysing LFIAs still rely heavily on sub-optimal human readout and rudimentary end-point analysis. This negatively impacts both testing accuracy and testing times, ultimately lowering diagnostic throughput. Herein, we present an automated computational imaging method for processing and analysing multiple LFIAs in real-time and in parallel. This method relies on the automated detection of signal intensity at the test line, control line, and background, and employs statistical comparison of these values to predictively categorise tests as "positive", "negative", or "failed". We show that such a computational methodology can be transferred to a smartphone and detail how real-time analysis of LFIAs can be leveraged to decrease the time-to-result and increase testing throughput. We compare our method to naked-eye readout and demonstrate a shorter time-to-result across a range of target antigen concentrations and fewer false negatives compared to human subjects at low antigen concentrations.

Oversizing of self-expanding Nitinol vascular stents - A biomechanical investigation in the superficial femoral artery.

Despite being commonly employed to treat peripheral artery disease, self-expanding Nitinol stents are still associated with relatively high incidence of failure in the mid- and long-term due to in-stent restenosis or fatigue fracture. The practice of stent oversizing is necessary to obtain suitable lumen gain and apposition to the vessel wall, though it is regarded as a potential cause of negative clinical outcomes when mis-sizing occurs. The objective of this study was to develop a computational model to provide a better understanding of the structural effects of stent sizing in a patient-specific scenario, considering oversizing ratio OS, defined as the stent nominal diameter to the average vessel diameter, between 1.0 and 1.8. It was found that OS < 1.2 resulted in problematic short-term outcomes, with poor lumen gain and significant strut malapposition. Oversizing ratios that were in the range 1.2 ≤ OS ≤ 1.4 provided the optimum biomechanical performance following implantation, with improved lumen gain, reduced incomplete stent apposition and favourable predicted long-term fatigue performance. Excessive oversizing, OS > 1.4, did not provide any further benefit in outcomes, showing limited increases in lumen gain and unfavourable long-term performance, with higher mean strain values predicted from the fatigue analysis. Therefore, our findings predict that the optimal oversizing ratio for self-expanding Nitinol stents is in the range of 1.2 ≤ OS ≤ 1.4, which is similar to clinical observations, with this study providing detailed insight into the biomechanical basis for this.

Simplifying the complex: accessible microfluidic solutions for contemporary processes within in vitro diagnostics.

In vitro diagnostics (IVDs) form the cornerstone of modern medicine. They are routinely employed throughout the entire treatment pathway, from initial diagnosis through to prognosis, treatment planning, and post-treatment surveillance. Given the proven links between high quality diagnostic testing and overall health, ensuring broad access to IVDs has long been a focus of both researchers and medical professionals. Unfortunately, the current diagnostic paradigm relies heavily on centralized laboratories, complex and expensive equipment, and highly trained personnel. It is commonly assumed that this level of complexity is required to achieve the performance necessary for sensitive and specific disease diagnosis, and that making something affordable and accessible entails significant compromises in test performance. However, recent work in the field of microfluidics is challenging this notion. By exploiting the unique features of microfluidic systems, researchers have been able to create progressively simple devices that can perform increasingly complex diagnostic assays. This review details how microfluidic technologies are disrupting the status quo, and facilitating the development of simple, affordable, and accessible integrated IVDs. Importantly, we discuss the advantages and limitations of various approaches, and highlight the remaining challenges within the field.

Multiscale agent-based modeling of restenosis after percutaneous transluminal angioplasty: Effects of tissue damage and hemodynamics on cellular activity.

BACKGROUND: Restenosis following percutaneous transluminal angioplasty (PTA) in femoral arteries is a major cause of failure of the revascularization procedure. The arterial wall response to PTA is driven by multifactorial, multiscale processes, whose complete understanding is lacking. Multiscale agent-based modeling frameworks, simulating the network of mechanobiological events at cell-tissue scale, can contribute to decipher the pathological pathways of restenosis. In this context, the present study proposes a fully-automated multiscale agent-based modeling framework simulating the arterial wall remodeling due to the wall damage provoked by PTA and to the altered hemodynamics in the post-operative months. METHODS: The framework, applied to an idealized femoral artery model, integrated: (i) a PTA module (i.e., structural mechanics simulation), computing the post-PTA arterial morphology and the PTA-induced damage (ii) a hemodynamics module (i.e., computational fluid dynamics simulations), quantifying the near-wall hemodynamics, and (iii) a tissue remodeling module simulating cellular activities through an agent-based model. RESULTS: The framework was able to capture relevant features of the 3-month arterial wall response to PTA, namely (i) the impact of the PTA-induced damage and altered hemodynamics on arterial wall remodeling, including the local intimal growth at the most susceptible regions (i.e., elevated damage levels and low wall shear stress), (ii) the lumen area temporal trend resulting from the interaction of the two inputs, and (iii) a 3-month lumen area restenosis of ∼25%, in accordance with clinical evidence. CONCLUSIONS: The overall results demonstrated the framework potentiality in capturing mechanobiological processes underlying restenosis, thus fostering future application to patient-specific scenarios.

Superficial femoral artery stenting: Impact of stent design and overlapping on the local hemodynamics.

BACKGROUND: Superficial femoral arteries (SFAs) treated with self-expanding stents are widely affected by in-stent restenosis (ISR), especially in case of long lesions and multiple overlapping devices. The altered hemodynamics provoked by the stent is considered as a promoting factor of ISR. In this context, this work aims to analyze the impact of stent design and stent overlapping on patient-specific SFA hemodynamics. METHODS: Through a morphing technique, single or multiple stents were virtually implanted within two patient-specific, post-operative SFA models reconstructed from computed tomography. The stented domains were used to perform computational fluid dynamics simulations, quantifying wall shear stress (WSS) based descriptors including time-averaged WSS (TAWSS), oscillatory shear index (OSI), transverse WSS (transWSS), and WSS ratio (WSSRATIO). Four stent designs (three laser-cut - EverFlex, Zilver and S.M.A.R.T. - and one prototype braided stent), and three typical clinical scenarios accounting for different order of stent implantation and overlapping length were compared. RESULTS: The main hemodynamic differences were found between the two types of stent designs (i.e. laser-cut vs. braided stents). The braided stent presented lower median transWSS and higher median WSSRATIO than the laser-cut stents (p < 0.0001). The laser-cut stents presented comparable WSS-based descriptor values, except for the Zilver, exhibiting a median TAWSS ∼30% higher than the other stents. Stent overlapping provoked an abrupt alteration of the WSS-based descriptors. The overlapping length, rather than the order of stent implantation, highly and negatively impacted the hemodynamics. CONCLUSION: The proposed computational workflow compared different SFA stent designs and stent overlapping configurations, highlighting those providing the most favorable hemodynamic conditions.

A predictive multiscale model of in-stent restenosis in femoral arteries: linking haemodynamics and gene expression with an agent-based model of cellular dynamics.

In-stent restenosis (ISR) is a maladaptive inflammatory-driven response of femoral arteries to percutaneous transluminal angioplasty and stent deployment, leading to lumen re-narrowing as consequence of excessive cellular proliferative and synthetic activities. A thorough understanding of the underlying mechanobiological factors contributing to ISR is still lacking. Computational multiscale models integrating both continuous- and agent-based approaches have been identified as promising tools to capture key aspects of the complex network of events encompassing molecular, cellular and tissue response to the intervention. In this regard, this work presents a multiscale framework integrating the effects of local haemodynamics and monocyte gene expression data on cellular dynamics to simulate ISR mechanobiological processes in a patient-specific model of stented superficial femoral artery. The framework is based on the coupling of computational fluid dynamics simulations (haemodynamics module) with an agent-based model (ABM) of cellular activities (tissue remodelling module). Sensitivity analysis and surrogate modelling combined with genetic algorithm optimization were adopted to explore the model behaviour and calibrate the ABM parameters. The proposed framework successfully described the patient lumen area reduction from baseline to one-month follow-up, demonstrating the potential capabilities of this approach in predicting the short-term arterial response to the endovascular procedure.

3D modelling of drug-coated balloons for the treatment of calcified superficial femoral arteries.

BACKGROUND/OBJECTIVES: Drug-coated balloon therapy for diseased superficial femoral arteries remains controversial. Despite its clinical relevance, only a few computational studies based on simplistic two-dimensional models have been proposed to investigate this endovascular therapy to date. This work addresses the aforementioned limitation by analyzing the drug transport and kinetics occurring during drug-coated balloon deployment in a three-dimensional geometry. METHODS: An idealized three-dimensional model of a superficial femoral artery presenting with a calcific plaque and treated with a drug-coated balloon was created to perform transient mass transport simulations. To account for the transport of drug (i.e. paclitaxel) released by the device, a diffusion-reaction equation was implemented by describing the drug bound to specific intracellular receptors through a non-linear, reversible reaction. The following features concerning procedural aspects, pathologies and modelling assumptions were investigated: (i) balloon application time (60-180 seconds); (ii) vessel wall composition (healthy vs. calcified wall); (iii) sequential balloon application; and (iv) drug wash-out by the blood stream vs. coating retention, modeled as exponential decay. RESULTS: The balloon inflation time impacted both the free and specifically-bound drug concentrations in the vessel wall. The vessel wall composition highly affected the drug concentrations. In particular, the specifically-bound drug concentration was four orders of magnitude lower in the calcific compared with healthy vessel wall portions, primarily as a result of reduced drug diffusion. The sequential application of two drug-coated balloons led to modest differences (~15%) in drug concentration immediately after inflation, which became negligible within 10 minutes. The retention of the balloon coating increased the drug concentration in the vessel wall fourfold. CONCLUSIONS: The overall findings suggest that paclitaxel kinetics may be affected not only by the geometrical and compositional features of the vessel treated with the drug-coated balloon, but also by balloon design characteristics and procedural aspects that should be carefully considered.

Multiscale Computational Modeling of Vascular Adaptation: A Systems Biology Approach Using Agent-Based Models.

The widespread incidence of cardiovascular diseases and associated mortality and morbidity, along with the advent of powerful computational resources, have fostered an extensive research in computational modeling of vascular pathophysiology field and promoted in-silico models as a support for biomedical research. Given the multiscale nature of biological systems, the integration of phenomena at different spatial and temporal scales has emerged to be essential in capturing mechanobiological mechanisms underlying vascular adaptation processes. In this regard, agent-based models have demonstrated to successfully embed the systems biology principles and capture the emergent behavior of cellular systems under different pathophysiological conditions. Furthermore, through their modular structure, agent-based models are suitable to be integrated with continuum-based models within a multiscale framework that can link the molecular pathways to the cell and tissue levels. This can allow improving existing therapies and/or developing new therapeutic strategies. The present review examines the multiscale computational frameworks of vascular adaptation with an emphasis on the integration of agent-based approaches with continuum models to describe vascular pathophysiology in a systems biology perspective. The state-of-the-art highlights the current gaps and limitations in the field, thus shedding light on new areas to be explored that may become the future research focus. The inclusion of molecular intracellular pathways (e.g., genomics or proteomics) within the multiscale agent-based modeling frameworks will certainly provide a great contribution to the promising personalized medicine. Efforts will be also needed to address the challenges encountered for the verification, uncertainty quantification, calibration and validation of these multiscale frameworks.

Baseline local hemodynamics as predictor of lumen remodeling at 1-year follow-up in stented superficial femoral arteries.

In-stent restenosis (ISR) is the major drawback of superficial femoral artery (SFA) stenting. Abnormal hemodynamics after stent implantation seems to promote the development of ISR. Accordingly, this study aims to investigate the impact of local hemodynamics on lumen remodeling in human stented SFA lesions. Ten SFA models were reconstructed at 1-week and 1-year follow-up from computed tomography images. Patient-specific computational fluid dynamics simulations were performed to relate the local hemodynamics at 1-week, expressed in terms of time-averaged wall shear stress (TAWSS), oscillatory shear index and relative residence time, with the lumen remodeling at 1-year, quantified as the change of lumen area between 1-week and 1-year. The TAWSS was negatively associated with the lumen area change (ρ = - 0.75, p = 0.013). The surface area exposed to low TAWSS was positively correlated with the lumen area change (ρ = 0.69, p = 0.026). No significant correlations were present between the other hemodynamic descriptors and lumen area change. The low TAWSS was the best predictive marker of lumen remodeling (positive predictive value of 44.8%). Moreover, stent length and overlapping were predictor of ISR at follow-up. Despite the limited number of analyzed lesions, the overall findings suggest an association between abnormal patterns of WSS after stenting and lumen remodeling.

In-Stent Restenosis Progression in Human Superficial Femoral Arteries: Dynamics of Lumen Remodeling and Impact of Local Hemodynamics.

In-stent restenosis (ISR) represents a major drawback of stented superficial femoral arteries (SFAs). Motivated by the high incidence and limited knowledge of ISR onset and development in human SFAs, this study aims to (i) analyze the lumen remodeling trajectory over 1-year follow-up period in human stented SFAs and (ii) investigate the impact of altered hemodynamics on ISR initiation and progression. Ten SFA lesions were reconstructed at four follow-ups from computed tomography to quantify the lumen area change occurring within 1-year post-intervention. Patient-specific computational fluid dynamics simulations were performed at each follow-up to relate wall shear stress (WSS) based descriptors with lumen remodeling. The largest lumen remodeling was found in the first post-operative month, with slight regional-specific differences (larger inward remodeling in the fringe segments, p < 0.05). Focal re-narrowing frequently occurred after 6 months. Slight differences in the lumen area change emerged between long and short stents, and between segments upstream and downstream from stent overlapping portions, at specific time intervals. Abnormal patterns of multidirectional WSS were associated with lumen remodeling within 1-year post-intervention. This longitudinal study gave important insights into the dynamics of ISR and the impact of hemodynamics on ISR progression in human SFAs.

Impact of lower limb movement on the hemodynamics of femoropopliteal arteries: A computational study.

Femoropopliteal arteries (FPAs) are subjected to a wide range of deformations, mainly determined by leg movement. FPAs are often affected by atherosclerotic plaque development, presumably influenced by the biomechanics of surrounding tissues. Although abnormal hemodynamics in FPAs appears to be an important factor in driving plaque development, to date it has been investigated in few studies, in which the leg was modeled in either fixed straight or bent configuration. Hence, the current work investigates the impact of leg movement on FPA hemodynamics. An idealized model of FPA was created to perform moving-boundary computational fluid dynamics analyses. By mimicking hip rotation, knee flexion and complete movement of walking, the hemodynamics was compared between moving- and fixed-boundary models. Moreover, additional features affecting the hemodynamics (e.g. flow-rate curve amplitude, walking speed) were examined. Significant hemodynamic differences were found between the moving- and fixed-boundary models, with the leg movement inducing higher time-averaged wall shear stress (TAWSS) (up to 66%). The flow-rate amplitude and walking period were the most influential parameters (differences in TAWSS up to 68% and 74%, respectively). In conclusion, this numerical approach highlighted the importance of considering leg movement to investigate FPA hemodynamics, and it could be employed in future patient-specific analyses.

A fully coupled computational fluid dynamics - agent-based model of atherosclerotic plaque development: Multiscale modeling framework and parameter sensitivity analysis.

BACKGROUND: Peripheral Artery Disease (PAD) is an atherosclerotic disorder that leads to impaired lumen patency through intimal hyperplasia and the build-up of plaques, mainly localized in areas of disturbed flow. Computational models can provide valuable insights in the pathogenesis of atherosclerosis and act as a predictive tool to optimize current interventional techniques. Our hypothesis is that a reliable predictive model must include the atherosclerosis development history. Accordingly, we developed a multiscale modeling framework of atherosclerosis that replicates the hemodynamic-driven arterial wall remodeling and plaque formation. METHODS: The framework was based on the coupling of Computational Fluid Dynamics (CFD) simulations with an Agent-Based Model (ABM). The CFD simulation computed the hemodynamics in a 3D artery model, while 2D ABMs simulated cell, Extracellular Matrix (ECM) and lipid dynamics in multiple vessel cross-sections. A sensitivity analysis was also performed to evaluate the oscillation of the ABM output to variations in the inputs and to identify the most influencing ABM parameters. RESULTS: Our multiscale model qualitatively replicated both the physiologic and pathologic arterial configuration, capturing histological-like features. The ABM outputs were mostly driven by cell and ECM dynamics, largely affecting the lumen area. A subset of parameters was found to affect the final lipid core size, without influencing cell/ECM or lumen area trends. CONCLUSION: The fully coupled CFD-ABM framework described atherosclerotic morphological and compositional changes triggered by a disturbed hemodynamics.

Double-Kissing Nanocrush for Bifurcation Lesions: Development, Bioengineering, Fluid Dynamics, and Initial Clinical Testing.

BACKGROUND: When possible, a single-stent technique to treat coronary bifurcation disease is preferable. However, when 2 stents are required, there is scope to improve on existing techniques. The crush technique has already been improved with the introduction of double-kissing (DK) and minicrush. We sought to refine and simplify the minicrush technique, retaining its advantages while avoiding its disadvantages, by developing a DK nanocrush technique. METHODS: The DK nanocrush method allows complete lesion coverage of a bifurcation lesion without excessive metal layers. This is achieved by positioning the side branch (SB) stent with minimal protrusion into the main branch (MB), implantation of the SB stent with an undeployed balloon in the MB, immediate kissing-balloon inflation with formation of a minimal neocarina, stenting the MB, recrossing the proximal part of the SB without crossing a double metal layer, and final kissing. We demonstrate this technique with benchtop implantation, microscopic computed tomographic reconstruction, computational fluid dynamics (CFD) modelling, and clinically with the use of angiographic and intravascular imaging. RESULTS: The DK nanocrush was practically feasible and resulted in full ostial coverage. CFD analysis demonstrated minimally disturbed blood flow. The technique was successfully utilised in 9 patients with bifurcation lesions with excellent angiographic outcomes and no adverse events over 12 months. CONCLUSIONS: The DK nanocrush technique may represent the ultimate refinement of the original crush technique with a number of practical and theoretical advantages. It remains to be tested against other bifurcation techniques in prospective trials.

Computing patient-specific hemodynamics in stented femoral artery models obtained from computed tomography using a validated 3D reconstruction method.

Patients with peripheral artery disease who undergo endovascular treatment are often inflicted by in-stent restenosis. The relation between restenosis and abnormal hemodynamics may be analyzed using patient-specific computational fluid dynamics (CFD) simulations. In this work, first a three-dimensional (3D) reconstruction method, based on an in-house semi-automatic segmentation algorithm of a patient's computed tomography (CT) images with calcification and metallic artifacts, and thrombus removal is described. The reconstruction method was validated using 3D printed rigid phantoms of stented femoral arteries by comparing the reconstructed geometries with the reference computer-aided design (CAD) geometries employed for 3D printing. The mean reconstruction error resulting from the validation of the reconstruction method was ~6% in both stented and non-stented regions. Secondly, a patient-specific model of the stented femoral artery was created and CFD analyses were performed with emphasis on the selection of the boundary conditions. CFD results were compared in scenarios with and without common femoral artery bifurcation, employing flat or parabolic inlet velocity profiles. Similar helical flow structures were visible in all scenarios. Negligible differences in wall shear stress (<0.5%) were found in the stented region. In conclusion, a robust method, applicable to patient-specific cases of stented diseased femoral arteries, was developed and validated.

Impact of bioresorbable scaffold design characteristics on local haemodynamic forces: an ex vivo assessment with computational fluid dynamics simulations.

AIMS: Bioresorbable scaffold (BRS) regions exposed to flow recirculation, low time-averaged wall shear stress (TAWSS) and high oscillatory shear index (OSI) develop increased neointima tissue. We investigated haemodynamic features in four different BRSs. METHODS AND RESULTS: Fantom (strut height [SH] = 125 µm), Fantom Encore (SH = 98 µm), Absorb (SH = 157 µm) and Magmaris (SH = 150 µm) BRSs were deployed in phantom tubes and imaged with microCT. Both 2D and 3D geometrical scaffold models were reconstructed. Computational fluid dynamics (CFD) simulation was performed to compute TAWSS and OSI. Thicker struts had larger recirculation zones and lower TAWSS in 2D. Absorb had the largest recirculation zone and the lowest TAWSS (240 µm and -0.18 Pa), followed by Magmaris (170 µm and -0.15 Pa), Fantom (140 µm and -0.14 Pa) and Fantom Encore (100 µm and -0.13 Pa). Besides strut size, stent design played a dominant role in 3D. The highest percentage area adverse TAWSS (<0.5 Pa) and OSI (>0.2) were found for Fantom (56% and 30%) and Absorb (53% and 33%), followed by Fantom Encore (30% and 25%) and Magmaris (25% and 20%). Magmaris had the smallest areas due to a small footprint and rounded struts. CONCLUSIONS: Due to stent design, both Fantom Encore and Magmaris showed smaller TAWSS and OSI than Fantom and Absorb. This study quantifies which scaffold features are most important to reduce long-term restenosis.