Primary open angle glaucoma represents an eye disease that usually is associated with an increased intraocular pressure (IOP). Implants for micro-invasive glaucoma surgery (MIGS) are gaining importance as a promising option for IOP lowering. Currently available devices are implanted into the eye ab interno based on a clear corneal incision and drain aqueous humour into the schlemm’s canal, suprachoroidal or subconjunctival space. Fibrosis is known as a major limitation for long term success and often leads to the necessity of an additional medication or a surgical re-intervention. The current work focusses on the development of an antifibrotic drug-eluting coating for a minimally invasive implantable glaucoma microstent. Tubular microstent base bodies manufactured from a polycarbonate based silicone elastomer were spray-coated with a chloroform based mixture of the same polymer and the antifibrotic drug pirfenidone (PFD, P2116, Merck KGaA, Germany) in a polymer/drug ratio of 85/15% (w/w). Coating mass of 89 μg according to a drug loading of 1.96 μg mm-2 was aspired. Coating mass was measured using an ultramicrobalance (XP6U, Mettler-Toledo International, Inc., Switzerland). Glaucoma microstent prototypes with a drugeluting coating mass of (84 ± 19) μg (n = 12) were manufactured. Characterization by means of scanning electron microscopy (Quattro S, Thermo Fisher Scientific, FEI Deutschland GmbH, Germany) yielded a reproducible smooth surface of the coating. High performance liquid chromatography (KNAUER Wissenschaftliche Geräte GmbH, Germany) was used for analysis of drug release behaviour in 0.9% NaCl solution at 37°C. The in vitro PFDrelease is characterized by an initial burst phase of approximately 6 h followed by a more retarded release phase. The entire drug was released within 36 h (n = 3). Sterilization processing has a minor impact on drug release kinetics. Appropriate drug stability after sterilization could be proven. Future studies will focus on the antifibrotic properties of drug-eluting glaucoma microstents in animal studies.
Although the development of the transcatheter aortic valve (TAV) has saved many lives of inoperable patients and has a very good clinical outcome, concerns about valve thrombosis are increasing. Due to the potential risk of late clinically relevant events, the US Food and Drug Administration (FDA) suggests a careful systematic investigation of thrombosis and reduced leaflet motion related to hemodynamic changes induced by TAV implantation. Furthermore, recently published position papers of the ISO working group address numerical and experimental flow field assessment of TAV. In particular, pathologically high shear rates and a reduced washout of the sinuses may increase the risk of valve thrombosis and should therefore be investigated. By means of fluid-structure interaction (FSI) as a powerful in silico tool, the transient flow field in an aortic valve was analyzed. A linear elastic behavior was assumed for leaflet material properties (Young modulus: 10 MPa, Poisson ratio: 0.46 and leaflet material density: 1000 kg/m3) and blood was specified as a homogeneous, Newtonian and incompressible fluid (fluid density: 1060 kg/m3 and a dynamic viscosity: 0.0035 Pa s). In this numerical study we present a Eulerian approach, which is based on transport equation of the residence time (RT) as a passively transported scalar. It can be clearly seen that the RT is significantly higher in the sinus referred to the main flow. At time step t = 0.25 s, the average residence time in the main flow is RTavg ≈ 0.05 s, whereas RT ≈ 0.25 s in the sinus. In particular, RT is a valuable hemodynamic metric to quantify the washout of the sinus in order to evaluate the thrombogenic potential of TAV devices. Further studies will concentrate on particle image velocimetry measurements for validation purposes. In particular the velocity in the sinus and therefore the washout is one important hemodynamic key feature that has to be improved for future TAV designs.
Chronic venous insufficiency (CVI) is a common disease characterized by impaired venous drainage leading to congestion in the lower limbs. Currently, there are no artificial or biological venous valve prostheses commercially available. Previous minimally invasive design concepts failed to achieve sufficient long term results in animal or in vitro studies. The aim was to implement structural numerical simulation of clinically relevant loading cases for minimally invasive implantable venous valve prostheses. A bicuspid valve design was chosen as it showed superior results compared to tricuspid valves in previous studies. The selfexpanding support structure was developed by using diamond-shaped elements. Using finite-element analysis (FEA), various loading cases, including expansion and crimping of the stent structure and the release into a venous vessel, were simulated. A hyperelastic constitutive law for the vascular model was generated from uniaxial tensile test data of unfixated human vein walls. This study also compared numerical and experimental results regarding compliance and tensile tests to validate the vein material model. The calculated performance concerning expansion and crimping, as well as the release of the stent into a venous vessel, demonstrated the suitability of the stent design for minimally invasive application.
An established therapy for aortic valve stenosis and insufficiency is the transcatheter aortic valve replacement. By means of numerical simulation the valve dynamics can be investigated to improve the valve prostheses performance. This study examines the influence of the hemodynamic properties on the valve dynamics utilizing fluidstructure interaction (FSI) compared with results of finiteelement analysis (FEA). FEA and FSI were conducted using a previously published aortic valve model combined with a new developed model of the aortic root. Boundary conditions for a physiological pressurization were based on measurements of ventricular and aortic pressure from in vitro hydrodynamic studies of a commercially available heart valve prosthesis using a pulse duplicator system. A linear elastic behavior was assumed for leaflet material properties and blood was specified as a homogeneous, Newtonian incompressible fluid. The type of fluid domain discretization can be described with an arbitrary Lagrangian-Eulerian formulation. Comparison of significant points of time and the leaflet opening area were used to investigate the valve opening behavior of both analyses. Numerical results show that total valve opening modelled by FEA is faster compared to FSI by a factor of 5. In conclusion the inertia of the fluid, which surrounds the valve leaflets, has an important influence on leaflet deformation. Therefore, fluid dynamics should not be neglected in numerical analysis of heart valve prostheses.