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Modern technologies and methods such as computer simulation, so-called in silico methods, foster the development of medical devices. For accelerating the uptake of computer simulations and to increase credibility and reliability the U.S. Food and Drug Administration organized an inter-laboratory round robin study of a generic nozzle geometry. In preparation of own bench testing experiment using Particle Image Velocimetry, a custom made silicone nozzle was manufactured. By using in silico computational fluid dynamics method the influence of in vitro imperfections, such as inflow variations and geometrical deviations, on the flow field were evaluated. Based on literature the throat Reynolds number was varied Rethroat = 500 ± 50. It could be shown that the flow field errors resulted from variations of inlet conditions can be largely eliminated by normalizing if the Reynolds number is known. Furthermore, a symmetric imperfection of the silicone model within manufacturing tolerance does not affect the flow as much as an asymmetric failure such as an unintended curvature of the nozzle. In brief, we can conclude that geometrical imperfection of the reference experiment should be considered accordingly to in silico modelling. The question arises, if an asymmetric benchmark for biofluid analysis needs to be established. An eccentric nozzle benchmark could be a suitable case and will be further investigated.

The expansion capacity and accessibility of the side branch is essential for the stenting of complex bifurcations. Since previous measurement methods only provide limited information based on geometrical data of stent cells, a new measurement approach was developed which considers the mechanical deformation capacity of the stent design. This approach provides essential information on the stent with regard to the application of bifurcation stenting. Four different commercially available coronary stents (nominal diameter 3.0 mm) were dilated and a central strut cell was over-expanded by means balloon catheters of increasing nominal diameter (2.0 to 5.0 mm). After balloon inflation, the remaining cell size was investigated for maximum cell diameter and strut fractures. Large expansion capacity without cell damage is taken as a measure of the accessibility of the side branch. In none of the expansion experiments the desired target size could be achieved, which is due to the elastic recoil of the stent cells. Deviations from the target diameter between 14-38% were determined. However, larger diameters also showed a constriction of the balloon, so that in some cases the target diameter could not be achieved at all. No strut fractures occurred even at maximum balloon diameter and pressure (5.0 mm noncompliant balloons). As a result the side branch accessibility differs depending on the individual stent designs. No particular risk for the stent was found by extensive overdilatation.

Background Percutaneous coronary interventions (PCI) of bifurcation stenoses are both complex and challenging. Stenting strategies share that the stents’ side cells must be carefully explored and appropriately prepared using balloons or stents. So far, stent manufacturers have not provided any information regarding side-branch expansion capacity of their stent platforms. Aims Given that drug-eluting stent (DES) information regarding their mechanical capacity of side-branch expansion is not available, we aimed to evaluate contemporary DES (Orsiro, BIOTRONIK AG; Xience Sierra, Abbott Vascular; Resolute Integrity, Medtronic; Promus Premier Select, Boston Scientific; Supraflex Cruz, Sahajan and Medical Technologies) by their side-branch expansion behavior using in vitro bench testing. Methods In this in vitro study, we analyzed five commercially available DES (diameter 3.0 mm), measuring their side-branch expansion following inflation of different high-pressure non-compliant (NC) balloons (balloon diameter: 2.00–4.00 mm), thereby revealing the morphological characteristics of their side-branch expansion capacities. Results We demonstrated that all tested contemporary DES platforms could withstand large single-cell deformations, up to 4.0 mm. As seen in our side-branch experiments, DES designs consisting of only two connectors between strut rings did not only result in huge cell areas, but also in larger cell diameters following side-branch expansion compared with DES designs using three or more connectors. Furthermore, the stent cell diameter attained was below the balloon diameter at normal pressure. Conclusions We recommend that the expansion capacity of side-branches should be considered in stent selection for bifurcation interventions.

While the current generation of devices for minimally invasive treatment of severe symptomatic aortic valve stenosis is based on xenogenic leaflet-material, artificial polymeric leaflet-structures represent a promising approach for future improvement of heart valve performance. For enhanced long-term success of polymeric leafletstructures, limitations regarding calcification and durability have to be addressed. The objective of the presented study was the development of a constitutive law representing the material properties of artificial polymeric leaflet-structures of transcatheter heart valve prostheses in numerical simulation to assess the in silico leaflet-performance. Mechanical characterization of cast films and nonwoven specimens of a polycarbonate based silicone elastomer were conducted by means of uniaxial tension and planar shear testing, respectively. For validation purposes, experimental data were compared with the results of finite-element analysis (FEA) using different hyperelastic models. Strain energy function for third-order ogden hyperelastic model achieved the best fit of the non-linear stress-strain behavior of the isotropic polymeric material with the experimental data. It was chosen for further FEA of valve leaflet-performance under physiological pressurization to analyze the suitability of various manufacturing processes for polymeric leafletstructures. Therefore a specific leaflet-design with a wall thickness of 400 μm was used. As a result of FEA, time dependent leaflet-deformation, leaflet coaptation surface area (CSA) and leaflet opening area (LOA) of cast and nonwoven leaflet-structures were calculated. While LOA was comparable for cast and nonwoven leaflet-structures, obtained leaflet-dynamics in a cardiac cycle under physiological pressurization demonstrated crucial influence of the manufacturing process. For nonwoven leafletstructures, an enhanced CSA could be demonstrated in comparison to cast structures. FEA using a validated hyperelastic constitutive law represents a useful tool for in silico performance evaluation of polymeric leaflet-structures under physiological loading and proves the suitability of the polymeric artificial leaflet-material for percutaneous heart valve prostheses.

BackgroundEndothelial healing after deployment of cardiovascular devices is particularly important in the context of clinical outcome. It is therefore of great interest to develop tools for a precise prediction of endothelial growth after injury in the process of implant deployment. For experimental investigation of re-endothelialization in vitro cell migration assays are routinely used. However, automatic analyses of live cell images are often based on gray value distributions and are as such limited by image quality and user dependence. The rise of deep learning algorithms offers promising opportunities for application in medical image analysis. Here, we present an intelligent cell detection (iCD) approach for comprehensive assay analysis to obtain essential characteristics on cell and population scale.ResultsIn an in vitro wound healing assay, we compared conventional analysis methods with our iCD approach. Therefore we determined cell density and cell velocity on cell scale and the movement of the cell layer as well as the gap closure between two cell monolayers on population scale. Our data demonstrate that cell density analysis based on deep learning algorithms is superior to an adaptive threshold method regarding robustness against image distortion. In addition, results on cell scale obtained with iCD are in agreement with manually velocity detection, while conventional methods, such as Cell Image Velocimetry (CIV), underestimate cell velocity by a factor of 0.5. Further, we found that iCD analysis of the monolayer movement gave results just as well as manual freehand detection, while conventional methods again shows more frayed leading edge detection compared to manual detection. Analysis of monolayer edge protrusion by ICD also produced results, which are close to manual estimation with an relative error of 13.2 %. In comparison, the conventional Canny method gave a relative error of 61 %. ConclusionThe results of our experiments indicate that deep learning algorithms such as our iCD have the ability to outperform conventional methods in the field of wound healing analysis. The combined analysis on cell and population scale using iCD is very well suited for timesaving and high quality wound healing analysis enabling the research community to gain detailed understanding of endothelial movement.

In-stent thrombosis is a major complication of stent implantations. Unlike pathological occurrences as in-stent restenosis for instance, thrombosis represents an acute event associated with high mortality rates. Experiments show that low wall shear stress promotes undirected endothelial cell coverage of the vessel wall and therefore increases the risk of thrombus formation. Stent design represents a crucial factor influencing the surface areas of low wall shear stress and thus the incidence of acute in-stent thrombosis. In this study, we present an optimization method for stent designs with minimized thrombosis risk. A generic stent design was developed, based on five different stent design parameters. Optimization was conducted based on computational fluid dynamics analysis and the gradient-free Nelder-Mead approach. For each optimization step, a numerical fluid simulation was performed in a vessel with a reference vessel diameter of 2.70 mm with stent-overexpansion ratio of 1.0:1.1. For each numerical fluid simulation a physiological Reynolds number of 250, resulting in a mean velocity of 0.331 m/s at the inlet and a laminar flow as well as stiff vessel walls were assumed. The impact of different stent designs was analyzed based on the wall shear stress distribution. As a basis for the comparison of different stent designs, a dimensionless thrombosis risk number was calculated from the area of low wall shear stress and the overall stented area. The first two optimization steps already provide a decrease of thrombosis risk of approximately 83%. In conclusion, computational fluid dynamic analyses and optimization methods usind the Nelder-Mead approach represent a useful tool for the development of hemodynamically optimized stent designs with minimized thrombosis risk.

For the treatment of severe symptomatic aortic valve stenosis, minimally invasive heart valve prostheses are increasingly used, especially for elderly patients. The current generation of devices is based on xenogenic leaflet material, involving limitations with regard to calcification and durability. Artificial polymeric leaflet-structures re-present a promising approach for improvement of valve performance. Within the current work, finite-element ana-lysis (FEA) design studies of polymeric leaflet structures were conducted. Design of an unpressurized and axially-symmetric trileaflet heart valve was developed based on nine parameters. Physiological pressurization in FEA was specified, based on in vitro hydrodynamic testing of a commercially available heart valve prosthesis. Hyper-elastic constitutive law for polymeric leaflet material was implemented based on experimental stress strain curves resulting from uniaxial tensile and planar shear testing. As a result of FEA, time dependent leaflet deformation of the leaflet structure was calculated. Obtained leaflet dynamics were comparable to in vitro performance of the analyzed prosthesis. As a major design parameter, the lunula angle has demonstrated crucial influence on the performance of the polymeric leaflet structures. FEA represented a useful tool for design of improved polymeric leaflet structures for minimally invasive implantable heart valve prostheses.

Computational fluid dynamics (CFD) is a powerful tool to extent knowledge of biomechanical processes in cardiovascular implants. To provide a standardized method the U.S. Food and Drug Administration (FDA) initialized a CFD round robin study. One of the developed benchmark standard models is a generic nozzle geometry, consisting of a cylindrical throat with a conical collector and sudden expansion on either side. Several fluid mechanical data obtained from international institutes by means of CFD and particle image velocimetry (PIV) measurements under different flow regimes (Re = 500, 2000, 3500, 5000 and 6500) are freely available. This database includes only steady state simulations. In this study we performed pulsatile CFD simulations to consider the physiological environment of the coronary vessels. Furthermore, the nozzle geometry was scaled down to coronary dimension (D inlet = 12 mm to 3 mm) while retaining the average Reynolds number Re = 500 constant. The pulsatile character is described by a Womersley number of Wo = 2.065. Our CFD code was previously validated by using FDA’s data for steady state inflow conditions. It could be shown that time averaged wall shear stress and shear stress values agree well with steady state results. We conclude that steady state simulations are valid for hemodynamic analyses if only time averaged values are needed. This could save computational costs of future hemodynamic investigations. In addition, this study expands FDA’s benchmark case by pulsatile inlet condition for further code validation. This could be necessary for the development of new numerical methods as well as for validation of CFD codes used in the approval process of medical devices.

For the investigation of reaction moments of wrist joint with external fixator, a test device was developed that allows a well-defined investigation of the joint loads during hand flexion movements. The reaction moments are considered as a measure for the joint loads due to the constraint forces, which occur with differences of the rotation axis of the fixator device from the physiological rotation axis of the wrist joint. The developed test device allows a dynamic momentum load application into the wrist by a servohydraulic testing machine. This testing device converts the force to a moment by a constant lever arm and allows thereby the measurement of the reaction moments by the force load cell of the testing machine. Measurements on cadaveric wrist joints with external fixator can be thereby performed under reproducible conditions. The cadaveric wrist joints can be integrally casted into bone cement and thereby clamped to the testing device. Preliminary experiments with artificial bones showed that forces within the measuring range of the load cell of the testing machine can be measured. The design of the test device is presented. Hence, the requirements for measurements of the reaction moments with wrists with external fixator for distal radius fractures under dynamic loads are created.