Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the anti-proliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease

Simulating Drug-Eluting Stents: Progress Made and the Way Forward

Drug-eluting stents have significantly improved the treatment of coronary artery disease. Compared with their bare metal predecessors, they offer reduced rates of restenosis and thus represent the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been around for over a decade, and while progress is continually being made, they are not suitable in all patients and lesion types. Furthermore there are still real concerns over incomplete healing and late stent thrombosis. In this paper, some modelling approaches are reviewed and the future of modelling and simulation in this field is discussed

On the role of specific drug binding in modelling arterial eluting stents

In this paper we consider drug binding in the arterial wall following delivery by a drug-eluting stent. Whilst it is now generally accepted that a non-linear saturable reversible binding model is required to properly describe the binding process, the precise form of the binding model varies between authors. Our particular interest in this manuscript is in assessing to what extent modelling specific and non-specific binding in the arterial wall as separate phases is important. We study this issue by extending a recently developed coupled model of drug release and arterial tissue distribution, and comparing simulated profiles of drug concentration and drug mass in each phase within the arterial tissue

Mathematical analysis of blood flow model through channels with flexible walls

A simplified mathematical model of blood flow through flexible arteries is developed and analyzed. The resulting system of non-linear, non-homogeneous PDE\u27s is analyzed numerically using the Richtmyer Lax-Wendroff method. Numerical and theoretical results show excellent agreement suggesting that in physiologically relevant situations shocks only develop outside the domain of interest. These results suggest that when the model assumptions are satisfied the model provides sufficient regularity to yield a physically reasonable representation of flow through a flexible artery. We conclude with a discussion of future directions for this model

is modeling stents still an important issue

Abstract Numerical models of cardiovascular devices have always appeared in literature studies few years after their use in clinical practice. As example, FDA approval of Palmaz-Schatz stent was in 1994, while the first numerical studies on a similar stent model appeared after 1999. The same temporal delay can be observed for degradable stents, transcatheter valves or more recently for devices like the stent retrievers. This observation does not necessarily mean that numerical modeling had not been used in the design of the stents or cardiovascular devices. Companies might have used numerical tools but not published the results. Was the publication activity committed mainly to the academic world? Or was the numerical modeling an exclusive academic activity until a few years ago? Modeling has intrinsic errors, while prototyping looks immune, as it is the natural design process for a company. The real world has always attracted more attention than the virtual world. Models are useful and the gap between the industrial production and numerical tools in the designing of devices is being reduced recently. Nowadays advances in medical images and augmentation of computer power allow to think of building real-time simulations as well as patient-specific models to be used to predict the device behavior; this is a plus that numerical modeling has over the traditional design process of cardiovascular devices. Furthermore, as in the past, the identification of new unknown problems/failures will always make the usage of numerical modeling a useful tool to explain the reasons of failure. The future in modeling stents is envisioned in their use for in silico trials and in the link between biology, engineering, and science

Heterogeneous Porous Media Simulation

Intracranial aneurysms are vascular disorders in which weakness in the wall of a cerebral artery or vein causes a localized dilation of the blood vessel. Flow diversion is an endovascular technique where a flow diverter stent is placed in the parent blood vessel to divert blood flow away from the aneurysm itself. Simulation by computational fluid dynamics is an attractive method to study flow diverters, particularly to model the small gaps between stent struts as a porous media. In many cases obstructions are not equal across the free medium and the porous one must be heterogeneous. Finite Volume Method solves numerical problems of computational fluid dynamics, splitting the region of interest in cells of small volumes. Porous media are usually modeled as a set of simulation cells described in a dictionary with constant porosity parameters (Homogeneous medium). An heterogeneous medium can be described as multiple homogeneous media, one by one. However, creating multiple homogeneous porous media is a tedious job if each simulation cell requires different parameters. Also, porous medium sets creates overheads on memory and processor load. The open source tool OpenFOAM is a open source C++ toolbox for field operations and partial differential equations solving using Finite Volume Method, including computational fluid dynamics. The tool is well prepared to describe heterogeneous fields. In this work, porous media coefficients are described as tensor fields. A steady state flow solver considering this fields is developed. The fidelity of the solver is then studied qualitatively and quantitatively.Fil: Dazeo, Nicolás Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Dottori, Javier Alejandro. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Boroni, Gustavo Adolfo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Larrabide, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Grupo de Plasmas Densos Magnetizados. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Grupo de Plasmas Densos Magnetizados; Argentin

Simulation of a mechanical thrombectomy device based in the use of self-expandable stents for the blood clots extraction

Recently, we have presented some studies concerning the analysis, design and optimization of one experimental device developed in the UK - GPTAD - which has been designed to remove blood clots without the need to make contact with the clot itself, thereby potentially reducing the risk of problems such as downstream embolisation. Based on the idea of a modification of the previous device, in this work, we present a model based in the use of stents like the SolitaireTM FR, which is in contact with the clot itself. In the case of such devices, the stent is self-expandable and the extraction of the blood clot is faciliatated by the stent, which must be inside the clot. Such stents are generally inserted in position by using the guidewire inserted into the catheter. This type of modeling could potentially be useful in showing how the blood clot is moved by the various different forces involved. The modelling has been undertaken by analyzing the resistances, compliances and inertances effects. We model an artery and blood clot for range of forces for the guidewire. In each case we determine the interaction between blood clot, stent and artery

Modelling arterial wall drug concentrations following the insertion of a drug-eluting stent

A mathematical model of a drug-eluting stent is proposed. The model considers a polymer region, containing the drug initially, and a porous region consisting of smooth muscle cells embedded in an extracellular matrix. An analytical solution is obtained for the drug concentration both in the target cells and the interstitial region of the tissue in terms of the drug release concentration at the interface between the polymer and the tissue. When the polymer region and the tissue region are considered as a coupled system it can be shown, under certain assumptions, that the drug release concentration satisfies a Volterra integral equation which must be solved numerically in general. The drug concentrations, both in the cellular and extracellular regions, are then determined from the solution of this integral equation and used in deriving the mass of drug in the cells and extracellular space

Identification of Hemodynamically Optimal Coronary Stent Designs Based on Vessel Caliber

Coronary stent design influences local patterns of wall shear stress (WSS) that are associated with neointimal growth, restenosis, and the endothelialization of stent struts. The number of circumferentially repeating crowns NC for a given stent de- sign is often modified depending on the target vessel caliber, but the hemodynamic implications of altering NC have not previously been studied. In this investigation, we analyzed the relationship between vessel diameter and the hemodynamically optimal NC using a derivative-free optimization algorithm coupled with computational fluid dynamics. The algorithm computed the optimal vessel diameter, defined as minimizing the area of stent-induced low WSS, for various configurations (i.e., NC) of a generic slotted-tube design and designs that resemble commercially available stents. Stents were modeled in idealized coronary arteries with a vessel diameter that was allowed to vary between 2 and 5 mm. The results indicate that the optimal vessel diameter increases for stent configurations with greater NC, and the designs of current commercial stents incorporate a greater NC than hemodynamically optimal stent designs. This finding suggests that reducing the NC of current stents may improve the hemodynamic environment within stented arteries and reduce the likelihood of excessive neointimal growth and thrombus formation