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Involuntary female infertility represents a sensitive issue, which is frequently caused by an impaired patency of the Fallopian tube. Current treatment options, such as in vitro fertilisation (IVF) or tubal reconstruction, are related to high costs or surgical risks. Therefore, a need for an alternative highly safe and effective minimally invasive therapy option is assumed. The current work presents a proof-of-concept for a novel microstent in combination with a delivery system for treatment of proximal Fallopian tube occlusions. For this purpose, a microstent prototype was implanted into a porcine Fallopian tube ex vivo using the presented delivery system. The results of the procedure were analyzed using a micro-computed tomography (μ-CT). Based on the μ-CT imaging, critical parameters of the microstent, such as radial patency, were assessed. The microstent implantation leads to an increased opening area of the Fallopian tube. Additionally, the microstent does not impair the anatomical shape of the tube epithelium and adapts well to the anatomical path. In further studies, the functionality of the Fallopian tube will be examined after microstent implantation in vivo.

The increasing trend of minimally invasive therapy methods for widespread diseases in the cardiovascular system, in the field of ophthalmology, ear, nose, and throat medicine, or gynecology, leads to an extensive demand for innovative microdevice manufacturing technologies. Femtosecond (fs)-laser technology offers a wide range of applications in the field of cutting, milling, and surface structuring on the micro- and nanometer scale. Ophthalmic devices for glaucoma therapy have dimensions in the submillimeter range. Irrespective of this, there are high demands on the safety and efficacy of these implants. Within the current study, fs-laser-based manufacturing technologies for functional elements of a novel microstent for glaucoma therapy were developed, considering potential industrial scalability. We successfully developed a mounting mechanism for quick and reproducible manufacturing of a micromechanical valve mechanism for safe regulation of intraocular pressure. Furthermore, we successfully developed a fs-laser-based process for manufacturing grooves as part of a fixation mechanism for a stable device positioning inside the eye. The results show that fs-laser manufacturing represents a promising technology for manufacturers of medical microdevices, such as ophthalmic microstents.

Besides visual assessment of the intra-vascular appearance, intravascular optical coherence tomography (IVOCT) enables precise diameter measurements within the coronary arteries. The current study presents an upgraded test setup allowing the investigation of the elastic properties of porcine coronary arteries ex vivounder pulsatile flow conditions. IV-OCT imaging was performed within the left circumflex artery of a porcine heart applying a normotensive and a hypertensive pressure regime at different pulse rates. Radial compliance was derived from the luminal diameter as well as intra-arterial pressure measurements. Test results show a significant reduction of radial compliance under pulsatile conditions, when compared to reference measurements under steady flow. The mean radial compliance decreased with increasing pulse rate, which can be attributed to the viscoelastic properties of the arterial wall.

Patients with cardiac arrhythmias are currently treated with conventional transvenous rhythm implants. Complications are frequently associated with intracardiac implanted leads primary insulated by silicone and polyurethane. However, experiences show that polyurethanes in particular are susceptible to various degradation mechanisms including hydrolysis, environmental stress cracking (ESC) and metal ion induced oxidation (MIO). In vivo, pacemaker leads are exposed to a complex thermal, chemical, mechanical and biological loading. The current study focusses on in vitro analyses to assess the biostability of Pellethane 2363 55D and the silicone MED 4765 as cardiac pacemaker lead insulations. Degradation processes were simulated in vitro in a load-free state and under static mechanical loading by subjecting a coaxial lead design to bending radii from 3 mm to 19 mm. Physiological environmental conditions were mimicked using a physiological saline solution and a tempered oxidative solution. Surface morphological and thermal analyses were performed before and after in vitro testing by means of scanning electron microscopy (SEM) and differential scanning calorimetry. Melting temperatures of silicones around 40°C were measured, before and after in vitro testing, respectively. Pellethane insulation layers had two endothermal melting regions at 100°C and 170°C before and a third melting region at 45°C after in vitro testing. The additional melting peak may indicate a change of thermal material properties due to degradation. SEM images showed degradation phenomena similar to in vivo studies, varying in severity and depending on the bending radius. Thus, the relevance of mechanical loading for in vitro replication of clinically relevant lead insulation degradation was demonstrated.

Computational fluid dynamics (CFD) has enormous potential for the development of novel cardiovascular implants. In particular, the evaluation of the thrombogenic potential of implants is gaining importance. For this purpose, the numerical model must represent the essential properties of the real system, i.e., an implant in the human blood circulation, in a suitable form. Due to its complexity, the model building process is crucial for the successful application of the model. Currently, there is no structured guideline for the application of numerical flow simulation to which model developers can refer. Based on NASA and ASTM, we present key aspects of the model building process using CFD for stent flow as an example.

Zusammenfassung Die minimalinvasive Implantation einer Transkatheter-Aortenklappenprothese (TAVR) hat sich zur Standardtherapie für Patienten mit schwerer Aortenklappenstenose und erhöhtem Operationsrisiko etabliert. Postoperative Komplikationen, wie die subklinische Klappenthrombose, rufen langfristig eine Funktionsstörung der TAVR hervor, die ohne Revisionstherapie zum Tod des Patienten führen kann. Mit der Abschätzung des Thromboserisikos von TAVR werden strömungsmechanische Mechanismen assoziiert. Die Particle Image Velocimetry (PIV) bietet ein etabliertes Messverfahren zur Bestimmung des Geschwindigkeitsfeldes einer TAVR, aus dem beispielsweise die Verweilzeit von Blut im Umfeld einer TAVR abgeleitet werden kann. Ein traversierbarer stereo-PIV Aufbau, bei dem zwei CMOS-Kameras im 45 ° Winkel zur Lichtschnittebene positioniert wurden, ermöglichte die Detektion von Tracerpartikeln in den relevanten Bereichen im Umfeld des TAVR. Mit einer geeigneten Messkammer, die in die hydraulische Nachbildung eines kardiovaskulären Kreislaufs implementiert wurde, konnte eine quasi-volumetrische Messung des physiologischen Geschwindigkeitsfeldes durchgeführt werden. Dafür wurde anhand radiologischer Daten eine realistische Implantationsumgebung rekonstruiert. Mit einem Blutersatzfluid (NaCl-Glycerin-Gemisch) wurde die normativ (ISO 5840:2021) geforderte kinematische Viskosität von ν = 3,5 cSt realisiert. Phasengetriggerte Aufnahmen ermöglichten die Messung zu definierten Zeitpunkten im kardiologischen Zyklus. Insgesamt ist es gelungen die komplexe Strömungstopologie mit dem dargestellten Messaufbau in allen relevanten Bereichen zu erfassen und damit zukünftig das Thromboserisiko abschätzen zu können.

Proximal occlusion of the Fallopian tube is one of the most common causes of female infertility. Due to the occlusion, the passage of the fallopian tubes is no longer given. Basically, there are two options for patients affected by this condition: cost-intensive in vitro fertilization (IVF) or surgery. The pregnancy rates of approximately 50% achieved with current treatment options are not satisfying. In this work, we present a Finite Element Analysis (FEA) model of a previously reported optimized microstent design for minimally invasive therapy of proximal tubal occlusion. Based on experimental investigations, the material model was set up and the simulation was validated. Comparison of the mechanical performance as an application related critical load case was in a good agreement. In this work, the proof of concept for the FEA model and the material model were carried out. In the future, the simulation will be used for further load cases such as the investigation of the bending stiffness and radial force and for the design optimization.

It is commonly accepted that hemodynamic situation is related with cardiovascular diseases as well as clinical post-procedural outcome. In particular, aortic valve stenosis and insufficiency are associated with high shear flow and increased pressure loss. Furthermore, regurgitation, high shear stress and regions of stagnant blood flow are presumed to have an impact on clinical result. Therefore, flow field assessment to characterize the hemodynamic situation is necessary for device evaluation and further design optimization. In-vitro as well as in-silico fluid mechanics methods can be used to investigate the flow through prostheses. In-silico solutions are based on mathematical equitation’s which need to be solved numerically (Computational Fluid Dynamics - CFD). Fundamentally, the flow is physically described by Navier-Stokes. CFD often requires high computational cost resulting in long computation time. Techniques based on deep-learning are under research to overcome this problem. In this study, we applied a deep-learning strategy to estimate fluid flows during peak systolic steady-state blood flows through mechanical aortic valves with varying opening angles in randomly generated aortic root geometries. We used a data driven approach by running 3,500 two dimensional simulations (CFD). The simulation data serves as training data in a supervised deep learning framework based on convolutional neural networks analogous to the U-net architecture. We were able to successfully train the neural network using the supervised data driven approach. The results showing that it is feasible to use a neural network to estimate physiological flow fields in the vicinity of prosthetic heart valves (Validation error below 0.06), by only giving geometry data (Image) into the Network. The neural network generates flow field prediction in real time, which is more than 2500 times faster compared to CFD simulation. Accordingly, there is tremendous potential in the use of AIbased approaches predicting blood flows through heart valves on the basis of geometry data, especially in applications where fast fluid mechanic predictions are desired.

Mitral regurgitation (MR) is the second most frequent indication for heart valve surgery and catheter interventions. According to European and US-American guidelines, transcatheter mitral valve repair in general and transcatheter edge-to-edge repair (TEER) in particular may be considered as a treatment option for selected high-risk patients. However, the biomechanical impact of TEERdevices on the mitral valve (MV) has not yet been fully understood. To address this problem, a 3D-Fluid-Structure Interaction (FSI) framework utilizing non-linear Finite Element Analysis (FEA) for the MV apparatus and Smoothed Particle Hydrodynamics (SPH) for the pulsatile fluid flow was developed and validated against in vitro data. An artificial MV-model (MVM) with a prolapse in the A2-P2 region and a custom-made TEER device implanted in the A2-P2 region were used for the in vitro investigations. In accordance with ISO 5910, projected mitral orifice areas (PMOA), flow rates as well as atrial and ventricular pressures were measured under pulsatile flow conditions before and after TEER device implantation. For the FSI-model, the MVM geometry was reconstructed by means of microcomputed tomography in a quasi-stress-free configuration. Quasi-static tensile test data was utilized for the development of linear- and hyperelastic material models of the chordae tendineae and leaflets, respectively. The fluid flow was modelled assuming an incompressible, homogenous Newtonian behaviour. Time-varying in vitro transmitral pressure loading was applied as a boundary condition. In vitro investigations show that TEER device implantation in the A2-P2 region effectively reduces the regurgitation fraction (RF) from 55 % to 13 %. Moreover, the comparison of experimental and numerical data yields a deviation of 2.09 % for the RF and a deviation of 0.40 % and 6.47 % for the maximum and minimum PMOA, respectively. The developed FSI-framework is in good agreement with in vitro data and is therefore applicable for the characterization of the biomechanical impact of different TEER devices under pulsatile flow conditions.

Implant devices for micro invasive glaucoma surgery (MIGS) are gaining increasing acceptance in clinical ophthalmic use. The implant requirements are defined in international standards, such as ANSI Z80.27-2014 and the 2015 Guidance for Industry and Food and Drug Administration Staff “Premarket Studies of Implantable Minimally Invasive Glaucoma Surgical (MIGS) Devices”. The exact fluid-mechanical characterization represents a crucial part of the development and approval of innovative implant devices for MIGS. The current work describes the development and preliminary validation of a versatile test facility for pivotal characterization of glaucoma drainage devices. The test setup enables a pressurization of test specimens by means of two water columns. For measurement of pressure and volume flow, a pressure transducer and a total of three liquid flow meters were implemented into the test setup. Validation was conducted by experimental pressureflow characterization of standardized tubes and a comparison to theoretical results according to Hagen Poiseuille's law for stationary laminar flow of a Newtonian fluid in a tube with a circular cross section. Ultrapure water at (35 ± 2) °C was used for the analyses. The developed test setup potentially enables pressure-flow characterization of test specimens in a wide flow range of 0 μl min-1 ≤ Q ≤ 5.000 μl min-1. The preliminary test facility validation showed a good agreement of measured and theoretical volume flow characteristics as a function of the pressure difference, in the currently investigated flow range of Q < 80 μl min-1. The developed test facility is suitable for pivotal in vitro characterization of glaucoma drainage devices. Future investigations will focus on the final validation of the whole flow range and on the use of the test facility for fluid-mechanical characterization of self-developed prototypes of glaucoma microstents as well as commercially available glaucoma drainage devices.

Paravalvular leakage (PVL) has a crucial impact on clinical outcomes of transcateheter aortic valve replacements (TAVR), especially the mortality increases dramatically with high-grade PVL. Furthermore, the calcification of the aortic annulus has a decisive influence on the PVL of TAVR. Therefore, we developed a technical model of a calcified aortic annulus and used it for the investigation of PVL in steady-state back-flow conditions. We investigated an Evolut PRO (Medtronic, Minneapolis, MN, USA), implanted the TAVR at different depths in the aortic annulus model ranging between 0 mm and -6 mm and characterized PVL in steady-state retrograde flow from 0 mmHg up to a maximum achievable pressure. The used test bench and detailed test method was described in previous studies. The aortic annulus model exhibits three elevations symmetrically distributed around the circumference. Depending on the degree of calcification the elevations reached 1 mm to 3 mm into the lumen. For the Evolut PRO bioprosthesis, a decreasing PVL was measured with increasing implantation depth. At an implantation depth of 0 mm (inflow of TAVR and annulus model at same height) maximum PVL was measured. Minimum PVL was measured at a height of -6 mm. Furthermore, even a small calcification of 1 mm led to a large increase in PVL. This trend continued with increasing height of the calcification. The maximum regurgitation of (2,025.21 ± 12.47) ml (n = 3 measurements) was measured at a pressure of 6 mmHg in the annulus model with 3 mm calcification. A test method to quantify PVL depending on annular calcification was successfully developed. Additionally, the influence of implantation depth on PVL was characterized. Due to the technical operating principle of the test bench, only a limited increase in pressure was possible when large PVL occurred. In this respect, the test bench must be optimized in the future.

Patients undergoing transcatheter aortic valve replacement (TAVR) may suffer severe clinical complications, caused by paravalvular leakage (PVL) which is defined as leakage between TAVR and aortic annulus. PVL is often facilitated by a severely calcified annulus. This limits the expansion of a self-expandable TAVR stent. To assess TAVR performance in terms of leakage, measurement of regurgitation fraction in a pathophysiological annulus is recommended according to ISO 5840. For this purpose, a configuration of a circular annulus with a calcification nodule has been proposed in the recently published ISO 5840. The impact of the proposed pathophysiological annulus model on the expansion of self-expandable TAVR stents and on the regurgitation fraction was investigated in this study. For this purpose, two commercially available selfexpandable TAVRs (Evolut R and Portico) were implanted in a calcified annulus model. Circular expansion of the TAVR stents was investigated based on μCT scans of the implanted TAVR. The calcification-induced area in which retrograde flow can occur during diastole was detected. These results were then compared with the experimentally determined regurgitation fraction obtained from pulse duplicator tests. The results of the μCT scans showed a continuous leakage area in the region of the annulus for the Evolut R compared to a locally larger leakage area of the Portico, which, however, reattaches to the annulus in the distal inflow region. The hydrodynamic measurements confirmed a smaller leakage in the pathological annulus for the Portico. In summary, it can be assumed that a continuous leakage area in the TAVR stent inflow region encourages the PVL of TAVR.

Glaucoma represents a chronic eye disease that becomes increasingly prevalent worldwide. Therapies are commonly based on the reduction of intraocular pressure (IOP). Implant devices for micro-invasive glaucoma surgery (MIGS) represent a promising therapy option in refractory cases but suffer from limitations in long term efficacy or from dislocation associated complications. Our approach of an innovative drug-eluting glaucoma microstent for MIGS was presented previously. Within the current work we developed concepts and prototypes of a mechanism for the fixation of our glaucoma microstent in the region of the corneal limbus. A tripod and a haptics design of the fixation mechanism were developed and manufactured. Semifinished products were tested with regard to dimensional stability and mechanical properties according to the standard ANSI Z80.27-2014. Considering the mechanical properties of ocular target tissues, a gelatin based in vitro model for the measurement of microstent retention force was developed. Retention force testing of microstent prototypes in vitro resulted in a proof of concept for the fixation mechanism. Future studies will focus on the use of smaller fixation fibers, for example commercially available suture material, and on an overall miniaturization of the fixation mechanism enabling the use of our applicator device with a 22G x 1½” cannula.

Optical coherence tomography (OCT) as imaging method is widely used in ophthalmology, oncology and cardiology. For intravascular imaging the OCT is used for pre-interventional as well as post-procedural assessments. Within the current study a test setup for ex vivo determination of the compliance of porcine coronary arteries via OCT is described. Diameter measurements based on OCT imaging were performed during consecutive pressurization of a porcine coronary artery from 40 to 200 mmHg in a physiological environment. The test results indicate that the radial compliance depends on the specific segment of the artery as well as the pressure range considered. The revealed compliance data can be used for numerical simulations of the vascular tissue as well as for optimization of in vitro test setups for pulsatile testing of vascular implants.

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.

Mitral regurgitation (MR) is the most prevalent valvulopathy in the USA and the second most prevalent valvulopathy in Europe. Despite excellent clinical results of surgical mitral valve repair (SMVR), transcatheter-based mitral valve repair (MVR) procedures emerged as a feasible treatment option for surgically inoperable or high-risk patients suffering from clinically relevant MR. The current study investigates the impact of device-induced coaptationwidth on the hydrodynamic performance of insufficient mitral valves (MV) during left ventricular (LV) systole. A non-calcified, pathological MV model (MVM) featuring a D-shaped MV annulus with an area of 7.6 cm2 and a flail gap in the A2-P2 region was employed in an experimental setup. Pressure gradient-volumetric flow rate (Δp-Q) relations were investigated for steady-state backward flow with transvalvular pressure gradients ranging from (0.75 ≤ Δp ≤ 177.36) mmHg. Glycerol-water mixture (36 % (v/v) glycerol in water) at 37 °C with a density of (1 098.2 ± 1.3) kg·m-3 and a dynamic viscosity of 3.5 mPa∙s was used as circulatory fluid. In order to determine the impact of the width of transcatheter MVR devices during LV-systole Δp-Q relations were investigated for three MVM-configurations: (i) MVM without MVR device, (ii) MVM with one MVR device and (iii) MVM with two MVR devices implanted in the A2-P2 region. The MVR devices were manufactured from steel sheets with a thickness of 0.2 mm and feature arm lengths of 9.0 mm and a width of 5.0 mm. The conducted investigations show that the implantation of MVR devices in the A2-P2 region prevents the manifestation of an A2-P2 flail gap and thereby effectively reduces the retrograde blood flow during the LV-systole by 13 % with one MVR device and 27 % with two MVR devices implanted. Thus, the application of two MVR devices with a combined device-induced width of 10 mm results in a better MR reduction than the implantation of one MVR device with a device-induced width of 5 mm.

Nanofiber nonwoven membranes produced by electrospinning provide the possibility to adjust mechanical material parameters as well as simultaneously the biologically relevant properties - a fundamental aspect in developing new implants and medical devices. Wettability and permeability are also of great importance, as they have a decisive influence on the release of drugs, cell attachment, degradability and finally the nutrient supply of the surrounding tissue. Within this work the wettability and permeability of several electrospun poly-L-lactide nonwovens, including different additives, were investigated and a correlation to membrane morphology was found. A potential modification of the permeability by the fluid viscosity was also investigated. The results form a fundamental building block in the development of permeable biodegradable implants and medical devices.

In case of cardiovascular implants classified as class III medical products there is a specific responsibility for manufacturers as well as regulatory authorities to follow international standards to guarantee for safety and efficacy. Fast developments of science and technology as well as novel clinical findings create permanent needs to match the standardization. Therefore, a set of international standards is analyzed with respect to their use for particular coronary drug-eluting stents and artificial heart valves. It was found that standards (ISO, ASTM) exist for general requirements on passive implants, but also specifically relate to arterial stents, stent grafts, bioresorbable and drug-eluting stents, as well as artificial heart valves. New work items address new methods for characterization of coating integrity, particulate matter and simulated use testing. European Medical Device Regulation (MDR) requires technical expertise and capacity at Notified Bodies supported by independent test laboratories. Generally, the interest in standardization from industry, test laboratories and authorities is high, but more input from medical experts would further improve the value of standardization and its relevance for safe and even more effective implants.

Due to the raising number of TAVR implantations (transcatheter aortic valve replacement), tests for durability and prevention of associated diseases are becoming increasingly important. Not only the anatomy but also the positioning of the TAVR is decisive for its clinical performance. A misalignment in the circumferential direction can influence the flow in the sinus and thus inhibit the blood supply of the coronary arteries and influence the thrombosis potential. Therefore, the modification of the flow field is investigated in this study. For the characterization of the flow fields the measuring method of digital particle image velocimetry is used. A hydraulic circulation model is used to generate physiological flow and pressure conditions. Additionally, an aortic root model with Sinus Valsalvae, which represents the implantation environment, was developed. A prototype of a TAVR was implanted aligned to the commissure lines of the native valve leaflets on the one hand, and misaligned by 60 degree to the commissure of the native valves on the other hand. By determining the velocity vector fields, it could be shown that implantation of the TAVR with a commissureal misalignment influences the flow around the leaflets. A comparison of the flow fields shows that different recirculation areas occur. This is also indicated by a comparison of the mean velocities in the sinus and the observed shear rates. The influence of the altered flow field on the thrombosis and hemolysis potential should be investigated in future studies.

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.

To assess the hydrodynamic performance of transcatheter aortic valve prostheses (TAVP), in vitro test using pulse duplicators is required. Test conditions as well as minimum performance criteria are specified in ISO 5840- 3:2013 and ISO 5840-3:2019-draft. In the 2019 published draft, modifications regarding hydrodynamic testing are proposed. Among others, the geometrical configuration of the fixation has changed, with the intention to improve the anatomical representation as well as the comparability of results from different test laboratories. We analyzed the consequences of altered annulus fixations regarding native leaflets as well as a step in the proximal area of the protheses to prevent their migration. The analyses were conducted with regard to the degree of calcification of the annulus ring on hydrodynamic parameters. By using 3D stereolithography printing technology, molds for casting of silicone elastomer of annulus models with and without native leaflets were manufactured. A modular system enabled us to use the same annulus ring to model the degree of calcification as well as different step sizes. We performed in vitro hydrodynamic testing according to ISO 5840-3:2019-draft of a selfexpandable valve prototype with porcine pericardial leaflets by using a commercially available pulse duplicator system. As expected, regurgitation increases with increasing degree of calcification, whereby the use of a step has no influence on the backflow of fluid during diastole. The effective orifice area (EOA) of the valve showed a clear tendency with respect to radial protrusion of the step. The EOA decreased as the radial protrusion increased. We also present a suggestion to prevent migration without affecting the general test results, by using a novel step design. We also found that the novel annulus model with native leaflet drastically reduced the regurgitation.

The European Parliament and the European Council on May 26, 2017 decided to introduce the new regulatory framework for medical devices. The transitional period of the so called Medical Device Regulation (EU 2017/745, MDR) should end on May 26, 2020. Currently the European Commission is working on a proposal to postpone the application for one year to relieve pressure from all stakeholders allowing them to fully focus on priorities related to the coronavirus crisis. From this date or most likely from May 26, 2021, manufacturers must present a CE-certificate according to the new MDR requirements not only for novel medical devices, but also for approved medical devices which are already on the market. The MDR will significantly complicate the process of bringing medical devices into market due to the increased requirements for the CE-certification process, particularly concerning increased documentation effort. This involves a risk for the translation of innovative products due to an overload of the overall system (manufacturers, Notified Bodies, experts) and might lead to shrinkage of the product range of existing products. Thankfully, adaption of transitional periods, special regulations, extensions of deadlines and most probably postponement of the MDR application date will ensure that there will be no gaps in medical supply that endanger patients. Establishing and keeping the relevant regulatory expertise up to date and devoting the necessary financial, time and human resources that is the biggest immediate challenge the medium-sized medical technology sector is facing in the near future. The current article, written about one month before the initially expected end of the first transition period on May 26, 2020, summarized the main aspects of the current state of MDR implementation with respect to regulatory novelties, the current legal basis in Germany, transition periods and changes in the requirements of CE-certification relevant technical documentation. Furthermore, challenges for existing and innovative medical devices were shortly discussed using a new stent based therapy of the proximal Fallopian tubal stenosis and transcatheter aortic valve implantation as two examples.

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.

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.

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.

The formation of a thrombus is associated with dramatic consequences for the patient, such as increased risks of neurologic events and myocardial infarction or even death. A pathologically altered blood flow is associated with these complications. Consequently, a consistent fluid-mechanical analysis of implants, such as coronary stents, must be carried out. Computational fluid dynamics (CFD) is an important in silico tool for the analysis of different stent designs. Using three different generic stent designs (closed-cell, open-cell and helical), CFD could be performed with the OpenFOAM software package. The stents were implemented in a vascular model having a fully developed Hagen-Poiseuille velocity profile (umean = 0.6 m/s) as inlet condition. In combination with the dynamic viscosity of the Newtonian test fluid of 6.04·10-5m2/s, Reynolds numbers up to 460 were achieved. Spatially high-resolved velocity fields from measurements in the magnetic resonance tomograph (magnetic resonance velocimetry, MRV) were available for validation. The velocity field was compared in selected cross sections and longitudinal sections. The difference of the main flow proximal and distal to the stent models were below 6 %. In addition, a similar flow topology could be quantified using the Q-criterion. Due to the very good agreement of the numerical results with the MRV-measurements, the numerical method has been applied to further analysis of stent designs regarding to time average wall shear stress (TAWSS) distribution on the luminal vessel surface (surface area with TAWSS < 0.4 Pa was related to overall vessel surface) under pulsatile conditions. Although all stent designs have the same square cross-section, a large influence of the stent design on WSS distribution could be observed (closedcell vs. helical = -50.2 %; open-cell vs. helical = -38.5 %). By using validated CFD it was possible to quantify the hemodynamic benefit of helical stent design in terms of thrombosis potential.

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.

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.

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.

Electrospinning is a method for producing fibrous polymer scaffolds that can be applied in drug delivery systems as well as for polymer-based implants. Biodegradable polymers for the purpose of cardiac tissue engineering are often applied as fibrous scaffolds for morphological mimikry of natural matrices but also drugeluting approaches are very promising. Hydrolytic degradation is one of the key parameters for successful application. The focus of our investigations is on monitoring accelerated in vitro degradation of electrospun nonwoven scaffolds. In the presented study degradation of poly(Llactide) is accelerated by alkaline hydrolysis. The process is characterized by weight loss, loss of molecular mass, surface morphology and thermal behavior of nonwoven samples, showing a fast degradation of the fibrous material within two weeks.

Glaucoma represents the leading cause of irreversible blindness worldwide. Therapeutic approaches are based on the lowering of intraocular pressure (IOP). Micro-invasive glaucoma surgery (MIGS) offers perspectives for implant based IOP-reduction with reduced complication rates compared to conventional surgical approaches. Nevertheless, available devices suffer from complications like hypotony and fibrotic encapsulation. The current work focuses on the development of a minimally invasive implantable drugeluting microstent for the drainage of aqueous humour into suprachoroidal or subconjunctival space. Technical feasibility of a micro-scale resorbable nonwoven for the prevention of hypotony and of a drug-eluting coating for the prevention of fibrosis is assessed. Microstent base bodies with a length of 10 mm and an inner/outer diameter of 0.20 mm / 0.35 mm were manufactured. For the prevention of hypotony, resorbable nonwovens with an adequate flow resistance of 1.543 mmHg/μl min-1 were manufactured in the inflow area of microstents. A drug-eluting coating in the outflow area of microstents was developed based on the model drug fluorescein diacetate. Micro-invasive ab interno implantation of a microstent prototype into suprachoroidal space of a porcine eye post mortem was successfully performed, using an injector device. Future studies will focus on the development of an antifibrotic drug-eluting coating and further in vitro, ex vivo and in vivo testing of the devices.

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.

In tissue engineering and regenerative medicine mesenchymal stem cells (MSC) are widely used to replace and restore the function of dysfunctional or missing tissue. Recent studies have shown significant enhancements of the in vivo healing process following dentofacial bone augmentation procedures employing stem cell-loaded xenografts. We conducted experimental and numerical investigations in perfusion flow bioreactor-xenograft-systems to identify flow conditions as well as bioreactor design features that allow for homogeneous MSC-distribution in Geistlich Bio- Oss Block xenografts. Pressure gradient - velocity characteristics and flow distributions were investigated experimentally and numerically for two bioreactor designs at steady-state flow conditions with Reynolds numbers (Re) ranging from 0.01 ≤ Re ≤ 0.32. Distilled water at 20°C with a dynamic viscosity of 1.002 mPa∙s and a density of 998 kg/m3 was used. The geometry of the xenograft utilized in three-dimensional computational fluid dynamics (CFD) simulation was obtained by means of micro-computed tomography (μCT) at an isotropic spatial resolution of 9.5 μm. The permeability values calculated from the experimental data are in good accordance with the numerical results. The investigations showed that the increase of the inflow- and outflow-area diameter, as well as the decrease of the volumetric flow rate, result in a decreasing heterogeneity of the flow distribution within the xenograft. The calculated wall shear stress rates in the three-dimensional (3D) scaffold range from 1∙10-12Pa ≤ τ ≤ 0.2 Pa. Experimentally validated CFD simulations introduced in this study provide an applicable tool to assess optimal flow conditions for homogeneous MSC distribution in bioreactor-xenograft-systems.

For the treatment of severe symptomatic aortic valve stenosis, minimally invasive heart valve prostheses have more recently become the lifesaving solution for elderly patients with high operational risk and thus, are often implanted in patients with challenging aortic root configuration. A correct prosthesis deployment and stent adaption to the target region is essential to ensure optimal leaflet performance and long-term prosthesis function. The objective of this study was the development of a suitable in silico setup for structural numerical simulation of a transcatheter aortic valve (TAV) in different cases of clinical relevance. A transcatheter valve prosthesis comprising an unpressurized trileaflet heart valve and an adapted stent configuration was designed. An aortic root (AR) model was developed, based on microcomputed tomography of a native healthy specimen. Using the finite-element analysis (FEA), various loading cases including prosthesis biomechanics with valve opening and closing under physiological pressure ratios throughout a cardiac cycle, prosthesis crimping as well as crimping and release into the developed AR model were simulated. Hyperelastic constitutive law for polymeric leaflet material and superelasticity of shape memory alloys for the self-expanding Nitinol stent structure were implemented into the FEA setup. Calculated performance of the valve including the stent structure demonstrated enhanced leaflet opening and closing as a result of stent deformation and redirected loading. Crimping and subsequent release into the AR model as well as the stent adaption to the target region after expansion proved the suitability of the TAV design for percutaneous application. FEA represented a useful tool for numerical simulation of an entire minimally invasive heart valve prosthesis in relevant clinical scenarios.

The implantation of an occluder in the left atrial appendage (LAA) is an emerging therapy for the treatment of patients suffering from atrial fibrillation and with a contraindication to oral anticoagulation. The LAA occluder (LAAO) provides a reduction of the potential risk of strokes by thromboembolism. Currently, only a few CE-approved devices are available on the market and the number of clinical trials is comparatively low. Furthermore, there is currently no standardized test method available for testing functionality of the occluder, especially for testing safe anchorage and permeability. Therefore, the aim of this study is to establish an in vitro test method to prove anchorage mechanism and permeability regarding thromboembolism of the LAAO under physiological conditions. A standardized technical and fully parameterized silicone model of a LAA, based on studies of different morphologies and sizes, was developed. The LAA model was mounted onto the left atrial chamber of a commercial pulse duplicator system to simulate physiological hemodynamic conditions. The test was performed using the Watchman device (Boston Scientific, USA; size: 31 mm). The inner implantation diameter of the LAA model was designed according to a target compression of 10% for the Watchman device in the implanted configuration. Furthermore, thrombus-like particles (n=150, d=1,7±0,05 mm) were added to represent the flushing of thrombi out of the LAA after device implantation. Within several cycles it was confirmed that no particles were washed out of the LAA model with the implanted occluder leading to a full protection against thromboembolism. It could also be shown that the occluder is firmly anchored in the LAA. Pressure measurements with sensors in the left atrium and in the LAA distal to the occluder could also show that the occluder has no influence on the pressure conditions in the LAA.

The implantation of transcatheter aortic valve prostheses (TAVP) for therapy of aortic valve stenosis shows more and more clinically non-inferiority results compared to surgical valve replacement in intermediate and low risk patients. Commonly clinically used TAVP are manufactured from chemically fixed xenograft leaflet material, e.g. bovine or porcine pericardium. While the clinical use of TAVP currently extends, challenges concerning valve durability and leaflet calcification have to be addressed. In this regard, artificial leaflet materials represent a promising option for a next generation of TAVP. As a first step for the development of TAVP from polymeric nonwoven, the aim of this study was to determine the influence of leaflet geometry on hydrodynamic performance of TAVP prototypes. Based on a parametric model of the valve leaflets, we varied the curvature of the belly line forming the leaflet coaptation area from an initial, quite concave, leaflet geometry with a value of 0.5° to an almost straight geometry for the leaflets with a value 0.15°. Manufacturing of TAVP prototypes was conducted by means of electrospinning technique with a polycarbonate based silicone elastomer. Hydrodynamic characterization according to ISO 5840-3 standards was performed using a pulse duplicator system with a heart rate of 70 BPM, systolic duration of 35%, mean aortic pressure of 100 mmHg and a stroke volume of 96 ml. Cardiac output as well as mean transaortic pressure gradient, closing volume, leakage volume and regurgitation were measured to compare the different leaflet geometries. To summarize, the curvature of the leaflets’ belly has a crucial impact on TAVP hydrodynamics under physiological test conditions. In particular, the opening and closing behavior is strongly influenced by a steeper curvature leading to larger closing volumes and higher regurgitant fractions. Further studies are planned to identify an optimum with respect to leaflet material selection, leaflet geometry and hydrodynamic properties of TAVP.

Mitral regurgitation (MR) occurs with a prevalence of approximately 10 % in patients aged 75 years or older and therefore is one of the most frequent indications for heart valve surgery. During the last decade surgical mitral valve repair (MVR) procedures emerged as the gold standard for the treatment of clinically relevant MR. However, for surgically inoperable or high-risk patients transcatheter-based MVR devices present a valuable treatment option. Within the current study, we developed an experimental setup to investigate the hydrodynamic performance of transcatheterbased MVR devices in vitro. The bicuspid mitral valve (MV) model employed in the experimental setup features a D-shaped MV annulus with d1 = 26.30 mm, d2= 30.05 mm and chordae tendineae with a length of l1= 25 mm attached to two papillary muscle structures. Pressure gradient - volumetric flow rate (Δp-Q) relations were investigated for steady state backward flow with transvalvular pressure gradients ranging from 0.75 mmHg ≤ Δp ≤ 103.13 mmHg. Deionized water at 37 °C with a dynamic viscosity of 1.002 mPa∙s and a density of 998 kg/m3 was used. A test-chamber consisting of a press-fit MV holder and cylindrical in- and outflow tracts were developed. Different designs for the exchangeable press-fit MV holder were manufactured using additive manufacturing technologies providing an optimal fitting for variable MV sizes and pathologies. In- and outflow tracts featuring a diameter of d = 50 mm and a height of h = 60 mm were made from transparent polymethylmethacrylate to allow for easy optical access during measurements. The experimentally investigated Δp-Q relation yields a quadratic correlation for the open MV and a linear correlation for the closed MV. A transvalvular closing pressure of (4.94 ± 0.04) mmHg was measured for the MV model.

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.

In dentofacial surgery, augmentation procedures employing xenografts have become a reliable treatment. Recent studies, however, have shown significant enhance-ments of the in vivo bone tissue augmentation using mesenchymal stem cells loaded into bone grafts. We conducted experimental and numerical investigations in flow perfusion systems to determine flow conditions which allow for homogenous stem cell distribution in BioOss Block (Geistlich Pharma AG, Switzerland) xenografts. Pressure gradient-velocity characteristics and flow distributions were investigated experimentally and numerically at steady state flow conditions with Reynolds numbers (Re) ranging from 0.01 ≤ Re ≤ 0.40. Distilled water at 20°C with a dynamic viscosity of 1.002 mPa.s and a density of 998 kg/m3 was used. The geometry utilized in three-dimensional computa-tional fluid dynamics (CFD) simulation was obtained by means of micro-computed tomography (μCT). Results of CFD analysis are in good accordance with experimental data. The comparison of the pressure gradient-velocity characteris-tics for experimental and numerical data yields a relative error of 3.6%. According to Darcy’s law for creeping fluid flow the experimentally determined permeability is 2.55.10-9 m2. Moreover, numerical flow distribution analysis shows an increasingly heterogenic streamline distribution for increasing Reynolds numbers. Experimentally validated CFD simulations introduced in this study provide a tool to assess optimal flow conditions for a homogenous stem cell distribution in perfusion flow systems.

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.

Assessment of hydrodynamic performance of transcatheter aortic valve prostheses (TAVP) in vitro is es-sentially in the fields of development and approval of novel implants. For the prediction of clinical performance, in vitro testing of TAVP allows for benchmarking of different devic-es, likewise. In addition to the implant itself, also the testing environment has a crucial influence on leaflet dynamics and quantitative test results like effective orifice area (EOA) or aortic regurgitation. Therefore, within the current study we developed simpli-fied physiological and pathophysiological vessel models of the aortic root as a tool for in vitro hydrodynamic testing of TAVP in idealized and worst case conditions. We used 3D printing and silicone cast molding for manufacturing of aortic root models with variable degree of stenosis. Design of aortic roots with normal, mild and severe stenosis was developed according to Reul et al. For manufacturing of tripartite cast-ing molds, a 3D printer was used. Both outer mold parts and the mold core were manufactured from polylactide filament and water soluble polyvinylalcohol filament, respectively. In vitro hydrodynamic performance testing of an exemplary commercially available TAVP implanted in different aortic root models was conducted according to DIN EN ISO 5840-3:2013, using a pulse duplicator system. Manufactured aortic root models were highly transparent, dimensionally stable and therefore suitable for hydrodynamic testing of TAVP. Both, EOA and regurgitant fraction in-creased with increasing degree of stenosis from 1.6 ± 0.1 cm2 to 1.8 ± 0.1 cm2 and 8.6 ± 6.5% to 20.2 ± 4.2% (n = 30 cy-cles), respectively. We successfully developed a testing environment ena-bling sophisticated evaluation of hydrodynamic performance of TAVR in pathophysiological worst case conditions.

Alteration of the flow characteristics in coronary vessels is correlated with coronary heart disease (CHD). In particular, wall shear stress (WSS) appears to be a hemody-namic key factor in the genesis of CHD. Since computational fluid dynamics (CFD) is a well-known method for the inves-tigation of WSS, it may be a valuable tool for the prediction of CHD. Latest imaging techniques, such as optical coher-ence tomography (OCT) in conjunction with angiography deliver precise 2D data sets of patient-specific vessel geome-try, which can be used for CFD analysis. Current CFD stud-ies utilize patient-specific geometries, but are lacking well defined physiologic inflow conditions. In this study, we present an inflow mapping method for patient-specific arterial vessels, which is capable of consider-ing the influence of bifurcations located proximal of the OCT-data set. At first, the patient-specific vessel was recon-structed. For this purpose the OCT-based vessel cross sec-tions were arranged along an angiographic based vessel pathway. Secondly, we simulated the flow field in a generic bifurcation model by means of CFD. Thereafter the flow field of a side branch was extracted and transferred (mapped) to the inlet of the patient-specific vessel. To evaluate the influence of the physiological inlet the WSS distribution of the same patient-specific vessel was calculated using an axial-symmetric inflow condition. Analy-sis of the simulation data yielded deviations of the WSS distribution in the proximal vessel segment. A bifurcation, located upstream of the relevant vessel segment strongly affects the flow in the OCT-based vessel reconstruction and has a strong influence on the results of the numerical analy-sis. Therefore, it is important to implement not only the pa-tient-specific geometry, but also an inlet boundary condition adapted to the upstream velocity distribution reflecting the actual proximal flow situation of the vessel.

Venous ulcers of the lower limbs are one clinical manifestation of chronic venous insufficiency. Currently, there is no venous valve prosthesis available. This study presents novel venous valve prostheses made of threedimensional electrospun fibrous nonwoven leaflets. The aim of this study was to prove the feasibility of the manufacturing process as well as to investigate design features of the venous valve prostheses from a hemodynamic point of view. An adapted pulse duplicator system (ViVitrolabs, Victoria, BC, CA) was used for characterization of the hydrodynamic performance. For eight different venous valve prototypes flow rate, effective orifice area and regurgitation fraction was investigated in vitro. In particular, tricusp valve designs showed an up to 40% higher effective orifice area as well as 15% higher maximum flowrate compared to bicusp valve designs. However, the regurgitation fraction of the bicusp valve designs is up to 86% lower compared to tricusp valve. Additionally, the hemodynamic performance of the tricuspid valves showed a high sensitivity regarding the leaflet length. Bicuspid valves are less sensitive to changes of design parameters, more sufficient and therefore highly reliable.

Coronary diseases are the main reason for death in the western world. Bio-fluid mechanical correlations with arterial diseases are in the focus of our research. To treat occluded vessels, stents are implanted. Stent implantations can be associated with blood flow disruptions leading to restenosis or thrombosis formation. Numerical flow simulation is a promising tool to evaluate the hemodynamic performance of cardiovascular implants, but is resource-intensive in time and computational power. Therefore, a reduction in grid size would be beneficial due to economic exploitation of computational cost. The purpose of this numerical investigation is to substitute the computational domain of a distal stented bifurcation with a stented straight vessel by using the right inlet condition. The deviation of the results of the two different methods to simulate the blood flow situation in a bifurcation is marginal. This inlet can be used for standardised simulations of bifurcations were lesions commonly occur.