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Nitinol became one of the most prominent materials for biomedical devices. The unique properties such as the shape memory effect and the superelasticity enabled new applications, particularly in the field of stent technologies. Due to their thermosensitivity, manufacturing processes are required that control the heat accumulation in the material. Here we investigate the femtosecond laser ablation of Nitinol supported by a water flow inside the processed tube. We show that laser absorption in the water prevents annealing of the Nitinol, even for high pulse energies. Furthermore, we investigate the groove profiles by scanning electron microscopy and observe minor improvements in the processed structure when using water flow inside the tube. The results show that water-supported femtosecond laser ablation can be used to optimize the fabrication of medical devices such as cardiovascular stents and to reduce processing times.

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.

Bioresorbable nanofiber nonwovens with their fascinating properties provide a wide range of potential biomedical applications. Modification of the material enables the adjustment of mechanical and biological characteristics depending on the desired application. Due to the nanosized fiber network, post-production structuring is very challenging. Within this study, we use femtosecond laser technology for structuring permeable and resorbable electrospun poly-L-lactide (PLLA) membranes. We show that this post-production process can be used without disturbing the fiber network near the structured areas. Furthermore, the modification of the water permeability and mechanical characteristics due to the laser structuring was investigated. The results prove femtosecond laser technology to be a promising method for the adjustment of the membrane properties and which in consequence can help to optimize cell adhesion, enable revascularization and open up applications of nanofiber membranes in personalized medicine.

Titanium represents an important biomaterial for implantable medical devices. During medical device manufacturing by means of welding, implant structures are partially exposed to high temperatures. Additionally, active implants such as pacemakers can heat up during operation. Therefore, numerical studies of heat propagation within titanium structures represent an essential tool to assess functionality and safety of medical devices. The current study focusses on the development of a method for experimental validation of numerical heat transfer analysis of biomaterials such as titanium. Numerical heat transfer analysis was performed using the software Abaqus. A finite-element model was established including material properties such as density, thermal conductivity und specific heat capacity. Temperature distribution among a locally applied thermal load was calculated. Furthermore, effects such as convection were considered. For validation, an experimental setup was implemented according to the numerical calculation using a local heating tool. Heat propagation in the sample was determined, respectively. Radiation-based heat determination was performed using an infrared thermographic camera aligned parallel to the sample surface. Contact-based heat determination was performed using thermocouples fixed to the surface at defined distances from the point of local heat input. For evaluation of numerical and experimental results, temperature- time curves were compared for five distinct measuring points, respectively. While infrared thermography offers the advantage of non-contact measurements, difficulties may arise from the definition of correct emissivity and challenging sample surface characteristics, such as metallic reflectance and surface texture. The thermocouple-based temperature measurement shows a high sensitivity to local temperature changes, but it is not always suitable due to the influence on the sample by thermocouple fixation. Infrared thermography and thermocouple based temperature measurements represent suitable procedures for experimental validation of numerical heat transfer analysis of titanium. An individual decision for the most suitable method must be made considering the specific sample and its further application.

Continuous adaptation of international standards for medical devices requires recurrent modification of test benches. A universal control unit using an open software environment is presented to simplify the maintenance of various test benches. Our developed control unit is equipped with a Raspberry Pi 4, with standard communication interfaces and application-specific electronic assemblies. The software is based on Node-RED, a browser-based editor. A measuring setup was adapted for a flow perfusion system. Our control unit simplifies the handling of the flow perfusion system by controlling a hydraulic pump and all required valves. A software programmed PID algorithm adapts the speed of the pump to adjust the pressure automatically. Actuators like proportional pinch valves are handled to control volumetric flow and pressure within the circulation. Consequently, the user directly observes changes inside the system. The measured data are stored and are available for documentation.

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.

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.

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.

Magnetic nanoparticles are highly promising for the usage in various biomedical applications including magnetic particle imaging (MPI), cancer hyperthermia treatment or as drug carriers. The present study aims at assessing in vitro biocompatibility of two commercially available magnetic iron oxide nanoparticle formulations: dextran-based magnetic nanoparticle synomag-D and bionized nanoferrite BNF-starch. Biological performance of both nanoparticle formulations were studied in human endothelial cells by analyzing cell viability and nanoparticle internalization in order to judge their suitability as theranostics.

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.

The photon spin is an important resource for quantum information processing as is the electron spin in spintronics. However, for subwavelength confined optical excitations, polarization as a global property of a mode cannot be defined. Here, we show that any polarization state of a plane-wave photon can reversibly be mapped to a pseudospin embodied by the two fundamental modes of a subwavelength plasmonic two-wire transmission line. We design a device in which this pseudospin evolves in a well-defined fashion throughout the device reminiscent of the evolution of photon polarization in a birefringent medium and the behavior of electron spins in the channel of a spin field-effect transistor. The significance of this pseudospin is enriched by the fact that it is subject to spin-orbit locking. Combined with optically active materials to exert external control over the pseudospin precession, our findings could enable spin-optical transistors, that is, the routing and processing of quantum information with light on a subwavelength scale.

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.

Standardized methods and measures are ubiquitous in biomedical engineering and a key factor for the successful development and certification of novel biomaterials, implants or other medical devices. Hence, the development of standardized measurement techniques, which can be applied to nearly every material and device is of crucial importance. Within the current work, we introduce a method to evaluate the water permeability according to ISO/FDIS 7198. The setup was designed to determine the volumetric flow through a test sample for a given hydraulic pressure. One key feature is the effortless replacement of the chamber containing the test sample. The measurement technique can thus be applied to a variety of materials and medical devices. To demonstrate the functionality of the setup we fabricated nanofiber membranes using the process of electrospinning. Nonwovens with comparable thickness and varying morphology were analyzed with regard to water permeability. In particular the different fiber diameters as well as the modified inter-fiber distances result in large deviations of the water permeability. Furthermore, there are hints for a rearrangement of the nanofibers due to the applied hydraulic pressure. The developed measurement technique provides a powerful tool for the standardized quantification of the water permeability and can be applied to a variety of biomaterials and medical devices.

In recent years, a progressive interest in the implementation of wireless access to cardiovascular implants has been established. This manifests in new devices, such as arterial pressure sensors, or additional functionalities added to established implants like stents. However, common stent designs, possessing highly optimized mechanical properties, often consist of cylindrically arranged struts with connections in-between which can be considered as short-circuited inductive coils. As a consequence, the small inductance raises the resonance frequency, which may decrease the in vivo performance of the wireless connection between the stent and the external readout device. Thus, new designs were developed to overcome this limitation, for example by avoiding the short-circuit due to a helical arrangement of the struts. Within this work we compare the performance of a common stent design and a helical design by means of numerical simulations. We are using two designs which only differ in the arrangement of the struts. The electromagnetic and mechanical properties are investigated using a finitedifference time-domain algorithm and finite element method, respectively. We will show that a common stent design exhibits resonance frequencies in the gigahertz regime, much higher than the frequencies of comparable helical designs. Furthermore, we compare the mechanical performance of the two designs and reveal individual distinctions in the radial stiffness, bending stiffness, and the von Mises stress.

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.

Gold nanostructures have important applications in nanoelectronics, nano-optics as well as in precision metrology due to their intriguing opto-electronic properties. These properties are governed by the bulk band structure but to some extend are tunable via geometrical resonances. Here we show that the band structure of gold itself exhibits significant size-dependent changes already for mesoscopic critical dimensions below 30 nm. To suppress the effects of geometrical resonances and grain boundaries, we prepared atomically flat ultrathin films of various thicknesses by utilizing large chemically grown single-crystalline gold platelets. We experimentally probe thickness-dependent changes of the band structure by means of two-photon photoluminescence and observe a surprising 100-fold increase of the nonlinear signal when the gold film thickness is reduced below 30 nm allowing us to optically resolve single-unit-cell steps. The effect is well explained by density functional calculations of the thickness-dependent 2D band structure of gold.

The optimization of nonlinear optical processes at the nanoscale is a crucial step for the development of nanoscale photon sources for quantum-optical networks. The development of innovative plasmonic nanoantenna designs and hybrid nanostructures to enhance optical nonlinearities in very small volumes represents one of the most promising routes. In such systems, the upconversion of photons can be achieved with high efficiencies via third-order processes, such as third harmonic generation (THG), thanks to the resonantly-enhanced volume currents. Conversely, second-order processes, such as second harmonic generation (SHG), are often inhibited by the symmetry of metal lattices and of common nanoantenna geometries. SHG and THG processes in plasmonic nanostructures are generally treated independently, since they both represent a small perturbation in the light-matter interaction mechanisms. In this work, we demonstrate that this paradigm does not hold in general, by providing evidence of a cascaded process in THG, which is fueled by SHG and sizably contributes to the overall yield. We address this mechanism by unveiling an anomalous fingerprint in the polarization state of the nonlinear emission from non-centrosymmetric gold nanoantennas and point out that such cascaded processes may also appear for structures that exhibit only moderate SHG yields - signifying its general relevance in plasmon-enhanced nonlinear optics. The presence of this peculiar mechanism in THG from plasmonic nanoantennas at telecommunication wavelengths allows gaining further insight on the physics of plasmon-enhanced nonlinear optical processes. This could be crucial in the realization of nanoscale elements for photon conversion and manipulation operating at room-temperature., 25 pages, 4 figures

Coupling mechanical degrees of freedom with plasmonic resonances has potential applications in optomechanics, sensing, and active plasmonics. Here we demonstrate a suspended two-wire plasmonic nano-antenna acting like a nano-electrometer. The antenna wires are supported and electrically connected via thin leads without disturbing the antenna resonance. As a voltage is applied, equal charges are induced on both antenna wires. The resulting equilibrium between the repulsive Coulomb force and the restoring elastic bending force enables us to precisely control the gap size. As a result the resonance wavelength and the field enhancement of the suspended optical nano-antenna (SONA) can be reversibly tuned. Our experiments highlight the potential to realize large bandwidth optical nanoelectromechanical systems (NEMS).

The optimization of nonlinear optical processes at the nanoscale is a key challenge in nanoscience. In this framework, plasmon-enhanced nonlinear effects together with the development of innovative nanoantenna designs and hybrid nanostructures are receiving a lot of attention [1-2]. We recently devised a plasmonic nanoantenna working in the near-infrared region of the electromagnetic spectrum, which allows boosting the SHG efficiency. This is achieved by optimizing the nanoantenna geometry to feature (i) a double resonant response at both the excitation and emission wavelengths, (ii) a spatial overlap between the modes involved in the process and (iii) a broken symmetry, to enable dipole-allowed SHG. We found that this nanoantenna behaves like a strongly coherent nanoscale light source, featuring a marked THG along with an intense SHG [3-4]. We find evidence of a SHG-mediated cascaded effect in THG [5]. We have identified a THG polarization behavior that strongly deviates from that of a bulk (3)-mediated effect and unveils a significant contribution coming from the cascaded coherent sum of a SHG photon and a pump photon. References [1] Kauranen, M.; Zayats, A. V., Nature Photon. 2012, 6, 737-748. [2] Butet, J.; Brevet, P. F.; Martin, O. J. F., ACS Nano 2015, 9, 10545–10562. [3] Celebrano, M.; et al., Nat. Nanotechnol. 2015, 10, 412−417. [4] Sartorello, G.; et al., ACS Photon. 2016, 3, 1517−1522. [5] Mu, X.; et al., Y., Opt. Lett. 2000, 25, 117-119.

We developed a paradigm to optimize the second-order nonlinear response of plasmonic nanoantennas. Multiresonant nanostructures featuring a broken symmetry and spatial overlap between the involved modes show a nonlinear peak coefficient of 5 × 10-10.