Claire Conway

Structural Mechanics Predictions Relating to Clinical Coronary Stent Fracture in a 5 Year Period in FDA MAUDE Database.

Endovascular stents are the mainstay of interventional cardiovascular medicine. Technological advances have reduced biological and clinical complications but not mechanical failure. Stent strut fracture is increasingly recognized as of paramount clinical importance. Though consensus reigns that fractures can result from material fatigue, how fracture is induced and the mechanisms underlying its clinical sequelae remain ill-defined. In this study, strut fractures were identified in the prospectively maintained Food and Drug Administration’s (FDA) Manufacturer and User Facility Device Experience Database (MAUDE), covering years 2006–2011, and differentiated based on specific coronary artery implantation site and device configuration. These data, and knowledge of the extent of dynamic arterial deformations obtained from patient CT images and published data, were used to define boundary conditions for 3D finite element models incorporating multimodal, multi-cycle deformation. The structural response for a range of stent designs and configurations was predicted by computational models and included estimation of maximum principal, minimum principal and equivalent plastic strains. Fatigue assessment was performed with Goodman diagrams and safe/unsafe regions defined for different stent designs. Von Mises stress and maximum principal strain increased with multimodal, fully reversed deformation. Spatial maps of unsafe locations corresponded to the identified locations of fracture in different coronary arteries in the clinical database. These findings, for the first time, provide insight into a potential link between patient adverse events and computational modeling of stent deformation. Understanding of the mechanical forces imposed under different implantation conditions may assist in rational design and optimal placement of these devices.

Modelling of Atherosclerotic Plaque for Use in a Computational Test-Bed for Stent Angioplasty

A thorough understanding of the diseased tissue state is necessary for the successful treatment of a blocked arterial vessel using stent angioplasty. The constitutive representation of atherosclerotic tissue is of great interest to researchers and engineers using computational models to analyse stents, as it is this in silico environment that allows extensive exploration of tissue response to device implantation. This paper presents an in silico evaluation of the effects of variation of atherosclerotic tissue constitutive representation on tissue mechanical response during stent implantation. The motivation behind this work is to investigate the level of detail that is required when modelling atherosclerotic tissue in a stenting simulation, and to give recommendations to the FDA for their guideline document on coronary stent evaluation, and specifically the current requirements for computational stress analyses. This paper explores the effects of variation of the material model for the atherosclerotic tissue matrix, the effects of inclusion of calcifications and a lipid pool, and finally the effects of inclusion of the Mullins effect in the atherosclerotic tissue matrix, on tissue response in stenting simulations. Results indicate that the inclusion of the Mullins effect in a direct stenting simulation does not have a significant effect on the deformed shape of the tissue or the stress state of the tissue. The inclusion of a lipid pool induces a local redistribution of lesion deformation for a soft surrounding matrix and the inclusion of a small volume of calcifications dramatically alters the local results for a soft surrounding matrix. One of the key findings from this work is that the underlying constitutive model (elasticity model) used for the atherosclerotic tissue is the dominant feature of the tissue representation in predicting tissue response in a stenting simulation.

Stents: Biomechanics, Biomaterials, and Insights from Computational Modeling

Coronary stents have revolutionized the treatment of coronary artery disease. Improvement in clinical outcomes requires detailed evaluation of the performance of stent biomechanics and the effectiveness as well as safety of biomaterials aiming at optimization of endovascular devices. Stents need to harmonize the hemodynamic environment and promote beneficial vessel healing processes with decreased thrombogenicity. Stent design variables and expansion properties are critical for vessel scaffolding. Drug-elution from stents, can help inhibit in-stent restenosis, but adds further complexity as drug release kinetics and coating formulations can dominate tissue responses. Biodegradable and bioabsorbable stents go one step further providing complete absorption over time governed by corrosion and erosion mechanisms. The advances in computing power and computational methods have enabled the application of numerical simulations and the in silico evaluation of the performance of stent devices made up of complex alloys and bioerodible materials in a range of dimensions and designs and with the capacity to retain and elute bioactive agents. This review presents the current knowledge on stent biomechanics, stent fatigue as well as drug release and mechanisms governing biodegradability focusing on the insights from computational modeling approaches.

Strain-induced accelerated asymmetric spatial degradation of polymeric vascular scaffolds

Significance Bioresorbable scaffolds (BRS) were thought to represent the next cardiovascular interventional revolution yet they failed compared with metal stents. When BRS were tested using methods for MS, no signal of concern emerged––perhaps because BRS are not metal stents. BRS not only degrade, they also possess significant localized structural irregularities that cause asymmetric degradation. We posit these microstructural irregularities are responsible for variability in device performance in first-generation BRS. We correlated nonuniform degradation with variation in polymer microstructure and tolerance to integrated strain generated during fabrication and implantation. Differentiating failure modes in metallic and polymeric devices explains clinical results and suggests optimization strategies for the design and fabrication of next-generation BRS, indeed all devices using degradable materials. Polymer-based bioresorbable scaffolds (BRS) seek to eliminate long-term complications of metal stents. However, current BRS designs bear substantially higher incidence of clinical failures, especially thrombosis, compared with metal stents. Research strategies inherited from metal stents fail to consider polymer microstructures and dynamics––issues critical to BRS. Using Raman spectroscopy, we demonstrate microstructural heterogeneities within polymeric scaffolds arising from integrated strain during fabrication and implantation. Stress generated from crimping and inflation causes loss of structural integrity even before chemical degradation, and the induced differences in crystallinity and polymer alignment across scaffolds lead to faster degradation in scaffold cores than on the surface, which further enlarge localized deformation. We postulate that these structural irregularities and asymmetric material degradation present a response to strain and thereby clinical performance different from metal stents. Unlike metal stents which stay patent and intact until catastrophic fracture, BRS exhibit loss of structural integrity almost immediately upon crimping and expansion. Irregularities in microstructure amplify these effects and can have profound clinical implications. Therefore, polymer microstructure should be considered in earliest design stages of resorbable devices, and fabrication processes must be well-designed with microscopic perspective.

Fracture in drug-eluting stents increases focal intimal hyperplasia in the atherosclerosed rabbit iliac artery

Drug‐eluting stent (DES) strut fracture (SF) is associated with higher incidence of In‐stent restenosis (ISR)—return of blockage in a diseased artery post stenting—than seen with bare metal stents (BMS). We hypothesize that concomitance of drug and SF leads to greater neointimal response.

Arterial and Atherosclerotic Plaque Biomechanics with Application to Stent Angioplasty Modeling

This chapter provides a brief review of continuum mechanics in relation to application in vascular biomechanics. The initial focus is on arterial tissue, where fundamental constitutive representations, tissue anisotropy, tissue remodeling and damage modeling are overviewed. The focus then shifts to diseased tissue (atherosclerotic plaque tissue), where experimental mechanical characterization, and constitutive and damage modeling are reviewed. Conclusions are drawn on what has been achieved thus far, and the main challenges for the future in characterizing and modeling this complex tissue are identified. Finally, the application of the arterial mechanics in the computational modeling of the stent angioplasty procedure is considered, with future challenges identified.

Therapy going viral

Virus-loaded microparticles can successfully treat lung infections in mice. Virus-loaded microparticles can successfully treat lung infections in mice.

Shaking up cellular therapy

Stem cell preparation technique determines the outcome of transplant therapy for myocardial infarction. Stem cell preparation technique determines the outcome of transplant therapy for myocardial infarction.

The placenta as a source of vascular grafts

Decellularized human placental arteries show potential for use as small-diameter vascular grafts in a rodent model. Decellularized human placental arteries show potential for use as small-diameter vascular grafts in a rodent model.

Finding a broken heart

A noninvasive imaging method identifies acute heart transplant rejection. A noninvasive imaging method identifies acute heart transplant rejection.