bluuebunny/crossref_metadata_2025 huggingface dataset:
Global mapping of research trends on antibacterial activity of green silver nanoparticles
Authors: Okaiyeto Kunle , Omotuyi Idowu Olaposi , Oguntibeju Oluwafemi Omoniyi
Published: December 2021

Over the years, the quest for antibacterial agents from green nanoparticles has attracted great attention due to the global rise in the prevalence of multi-drug resistant bacteria. Although several studies on the antibacterial activity of plant-mediated silver nanoparticles have been documented, no bibliometric studies on the subject have been reported to date. As a result, the present study aimed to assess the global research trends on the antibacterial activity of green silver nanoparticles from 2000 to 2020. In the present study, we explored Science Citation Index Expanded (SCIE) to extract research articles written in English on the subject within the specified period. Two hundred and sixty-nine (269) eligible research articles were included in the bibliometric analysis and R-package “bibliometrix” was used to analyse the documents for annual scientific publications, authors’ impact, most relevant institutions, countries productivity, frequent words, co-occurrence network, co-citation network and authors/institutions/countries collaboration networks. Based on the analysis, the top three (3) authors, journals, institutions and countries were Kumar V (n = 5), Zangeneh MM (n = 5) and Oh BT (n = 4); King Saud University, Banaras Hindu University and Islamic Azad University; Journal of Cluster Science (n = 10), Applied Organometallic Chemistry (n = 8) and Microbial Pathogenesis (n = 8); India, Iran, and Korea. The study findings highlighted the gaps in a research collaboration that negate productivity. Therefore, we are optimitic that this study would enlighten researchers in the field about the research lapses and the need for research collaboration in future studies.
Концепт низ: семантика базових слів
Authors: Ястремська Тетяна
Published: December 2021

Верх / низ – просторова опозиція, яка не тільки демонструє орієнтацією об’єктів у просторі, уточнює просторову кваліфікацію частини об’єкта, а й окреслює і формує систему координат мовної (resp. діалектної) картини світу. У статті проаналізовано лексико-семантичні особливості одного із полюсів цієї опозиції – концепту низ, який у говорах української мови репрезентують базові слова низ, діл, під (спід). Семантику базових слів досліджено в межах семантичних полів («Рельєф», «Будівля», «Тіло», «Одяг і взуття», «Сінозаготівля», «Соціум» та ін.), а також відповідно до семантичних субкомплексів (‘частина об’єкта’, ‘край, межа’, ‘поверхня’). У дослідженні застосовано ономасіологічну модель опису – від значення до слова. Корпус джерел сформували діалектні й етнографічні тексти, словники, регіональні атласи та записи діалектного мовлення носіїв говорів української мови, а також історичні словники, які документують семантичні зміни в часі.
Słownictwo polskie w gwarach rosyjskich (na podstawie materiałów Словаря русских народных говоров)
Authors: Ananiewa Natalia
Published: December 2021

Na podstawie materiałów pierwszych tomów Słownika rosyjskich gwar ludowych w artykule dokonano analizy rosyjskiego słownictwa gwarowego, które prawdopodobnie powstało na skutek oddziaływania języka polskiego. Główne uzasadnienie kwalifikacji rosyjkiego wyrazu gwarowego jako ewentualnej pożyczki z polszczyzny stanowi jego lokalizacja: Smoleńszczyzna, Litwa, Łotwa i niektóre inne regiony. Analizowane są poszczególne części mowy i klasy leksykalno-semantyczne wyrazów samodzielnych.
Influence of silver/silver chloride electroless plating on the Shore hardness of polyurethane substrates for dry EEG electrodes
Authors: Fauzhan Warsito Indhika , Machts René , Griebel Stefan , Fiedler Patrique , Haueisen Jens
Published: December 2021

Dry electrodes enable a shorter preparation time for infant EEG. Since infant skin is more sensitive than adult skin, soft electrodes are required to reduce the mechanical stress for this sensitive skin. Thus, soft electrodes are crucial for eventual repetitive and long-term use like in neonatal intensive care units. A biocompatible polyurethane (PU) can be produced in low hardness resulting in a soft and flexible electrode substrate. Silver/silver chloride (Ag/AgCl) electroless plating provides a conductive, electrochemically stable coating but the process may alter the mechanical properties of the electrode substrate. In this study, we assess the hardness of PU material before and after Ag/AgCl plating. The test sample design for Shore hardness measurement is based on ISO 7619-1:2010. Sample production consists of a 3D print master model, silicone molding, PU casting, and finally electroless plating. UPX 8400-1 (Sika AG, Switzerland) is used for the sample substrates. Test samples are produced with 7 different Shore hardness (range A40-A95) and 14 samples (each hardness: 1 uncoated and 1 coated). The hardness measurements are carried out with a lever-operated test stand Shore hardness tester model with a digital hardness tester (TI-AC with HDA 100-1, KERN &SOHN GmbH, Germany).. It is shown that there is a hardness increase (Shore A) due to Ag/AgCl coating with a grand average of 1.1±0.7 (p<0.05). The largest increase of 2.1±0.2 is seen on the initial lowest Shore hardness sample (Shore hardness: 43.4±0.1). The absolute increase of hardness due to the Ag/AgCl coating decreases with increasing substrate hardness. It is concluded that there is no strong hardness increase of PU substrates due to Ag/AgCl plating. Therefore, the material is suitable as a soft electrode for repetitive and long-term use in infant applications.
Microchip Transfer Process for Implantable Flexible Bioelectronic Devices
Authors: Martens Julien , Gueli Calogero , Eickenscheidt Max , Stieglitz Thomas
Published: December 2021

The demands on flexible implants for recording of neural signals and electrical stimulating have increased in recent years with regard to their functionality, miniaturization, and spatial resolution. These requirements can be met best by embedding powerful complementary metal oxide semiconductor (CMOS) microchips into thin biocompatible polymer substrates. So-called chip-in-foil systems thus combine mechanical properties of a polymer substrate and performance of CMOS technology. The development of a process for direct transfer of multiple CMOS microchips (edge length <400 μm) simultaneously into thin polyimide (PI) substrates is subject of this study. It allows the use of standard microelectromechanical systems (MEMS) processes for further levelled superficial layer build-up. This is achieved with the help of a silicon carrier wafer equipped with cavities for precise chip placement and a sacrificial layer to facilitate release of the chip-in-foil systems. In a post-processing step all silicon chips are thinned down to 100 μm. With this process a transfer yield of 100 % (n = 34) was achieved for the silicon chips on a die level. Chip rotational error on substrates was determined to be as low as 0.21° ± 0.10°. Die adhesion was examined by shear tests, resulting in shear strength of 58.1 MPa ± 13.7 MPa, which dropped to 15.2 MPa ± 10.5 MPa after accelerated ageing in 60 °C phosphate buffered saline solution (PBS) for 16 days (equivalent to 78 days at 37 °C). This study demonstrated a reliable microchip transfer process with low positioning error into flexible PI substrates with post-processing thinning of the dies. The use of a carrier silicon wafer allowed precise electrical interconnect fabrication with standard MEMS processing techniques and without handling of thin and fragile chips. These results are a prerequisite to meet needs of reliability and structural biocompatibility in implantable flexible bioelectronic devices.
Movement filtered heart rate variability (HRV) data from a chest-worn sensor
Authors: Hanshans Christian , Broell Lukas M. , Plischke Herbert , Offenbaecher Martin , Zauner Johannes , Faust Moritz M. R. , Maisch Bettina , Kohls Niko , Toussaint Loren , Hirsch Jameson , Siros Fuschia M.
Published: December 2021

Recording of heart rate variability (HRV) is a noninvasive and continuous measurement method that allows investigating the autonomic nervous system (ANS) and its reaction to environmental influences. For a precise measurement of HRV data, a carefully chosen study design and environment is required to minimize secondary influences. One major influence to be avoided is movement. However, in the daily routine and for some scientific questions, movement can often not be avoided. If so, a manual or automated method to differentiate between artifacts caused by body movement and the actual psychophysiological effect is needed to ensure the data quality. In this approach, a chest-worn sensor was developed, that measures the heart rate using a single lead ECG and filters the measured change of the HRV caused by movement. Data from an integrated accelerometer is used to detect upper body movements that affect the resting heart rate. The movementcorresponding time stamps are then used to filter the Interbeat Intervals (IBI) accordingly. Functionality and effectiveness of the sensor system have been tested against state-of-the art sports- or clinical devices in varying scenarios. As our test series showed, motion filtering has a decisive effect when motion occurs, two-thirds of all cases showed a significant effect of motion filtering, with small to medium effect sizes for the parameters SD2, SD2/SD1, and SDNN. Thereby, automatic filtering of motion artifacts can help to significantly reduce the need for costly post-processing of distorted data sets. The results show a better data quality of HRV measurement, a method that is commonly used for the investigation of physiological processes in the field of chronic pain, psychology, psychiatry, or sports medicine.
A neuromonitoring framework supporting the intraoperative placement of an epidural spinal cord electrode array for functional restoration in people with paraplegia
Authors: Schöfer Patrick , Lente Kornelius , Wegner Celine , Kogut Andreas , Rupp Rüdiger , Krüger Thilo B.
Published: December 2021

Targeted stimulation of dorsal nerve roots of the lumbosacral spinal cord (SC) represents a promising way to improve lower extremity functions for people with paraplegia due to SC injury. Stimulation pulses are selectively applied at different segments of the SC by means of an implanted electrode array. For an optimal clinical outcome, correct positioning of the array in rostrocaudal and mediolateral direction of the SC is essential. We developed a neuromonitoring framework to support the neurosurgeon during the implantation procedure by automated stimulation and real-time analysis of evoked muscular responses. For the implementation we developed and combined a new software with several hardware and software modules for intraoperative neuromonitoring. The new software coordinates different interfaces and components including a neurostimulator, a multiplexer module and a biosignal amplifier. In addition, a graphical user interface (GUI) was implemented, allowing control of the system and display of analyzed data. With the framework, stimulation sequences in respect to stimulation amplitudes and selection of contacts of the electrode array can be predefined and executed in an automated manner. Synchronously the evoked electromyographic responses of the target muscles can be recorded, analyzed and displayed together with the stimulation setup for visual evaluation. The framework serves as a fundamental basis for the integration of a clinical knowledge-based algorithm and the realization of a future neuromonitoring system for this purpose.
How Multimodal Examinations Can Increase Sustainable Student Gain by Aligning Teaching and Assessment
Authors: Gundlach Michael , Baumann Martin , Engelmann Ulrich M.
Published: December 2021

Modern industry and multi-discipline projects require highly trained individuals with resilient science and engineering back-grounds. Graduates must be able to agilely apply excellent theoretical knowledge in their subject matter as well as essential practical “hands-on” knowledge of diverse working processes to solve complex problems. To meet these demands, university education follows the concept of Constructive Alignment and thus increasingly adopts the teaching of necessary practical skills to the actual industry requirements and assessment routines. However, a systematic approach to coherently align these three central teaching demands is strangely absent from current university curricula. We demonstrate the feasibility of implementing practical assessments in a regular theory-based examination, thus defining the term “blended assessment”. We assessed a course for natural science and engineering students pursuing a career in biomedical engineering, and evaluated the benefit of blended assessment exams for students and lecturers. Our controlled study assessed the physiological background of electrocardiograms (ECGs), the practical measurement of ECG curves, and their interpretation of basic pathologic alterations. To study on long time effects, students have been assessed on the topic twice with a time lag of 6 months. Our findings suggest a significant improvement in student gain with respect to practical skills and theoretical knowledge. The results of the reassessments support these outcomes. From the lecturers´ point of view, blended assessment complements practical training courses while keeping organizational effort manageable. We consider blended assessment a viable tool for providing an improved student gain, industry-ready education format that should be evaluated and established further to prepare university graduates optimally for their future careers.
Finding an optimal dictionary of different wavelet types using sparse modeling to denoise ECG signal
Authors: Samann Fars , Schanze Thomas
Published: December 2021

Sparse signal modeling often reconstructs a signal with few atoms from a pre-defined dictionary. Hence the choice of wavelet dictionary that represents the sparsity of the target signal is crucial in sparse modeling approach. The challenge of finding an optimal dictionary of different wavelet types using sparse denoising model (SDM) to denoise ECG signal is investigated in this work. A method of finding an optimal wavelet dictionary from a set of orthogonal wavelet sub-dictionaries by the means of the best correlation with ECG signal, is developed. The highly correlated sub-dictionaries from three wavelet dictionaries, namely daubechies, symlets, coiflets and discrete cosine transform are combined to construct an overcomplete dictionary. The weight of Akaike’s information criterion and the signal-to-noise ratio improvement are considered as a criterion to evaluate the performance of the proposed SDM. The results indicate that multi-wavelet dictionary of different types is highly sparse and efficient in denoising the target signal, e.g., ECG.
A modular in vitro flow model to analyse blood-surface interactions under physiological conditions
Authors: Valtin Juliane , Behrens Stephan , Maitz Manfred F. , Schmieder Florian , Sonntag Frank , Werner Carsten
Published: December 2021

Newly developed materials for blood-contacting devices need to undergo hemocompatibility testing to prove compliance with clinical requirements. However, many current in vitro models disregard the influence of flow conditions and blood exchange as it occurs in vivo. Here, we present a flow model which allows testing of blood-surface interactions under more physiological conditions. This modular platform consists of a triple-pump-chip and a microchannel-chip with a customizable surface. Flow conditions can be adjusted individually within the physiological range. A performance test with whole blood confirmed the hemocompatibility of our modular platform. Hemolysis was negligible, inflammation and hemostasis parameters were comparable to those detected in a previously established quasi-static whole blood screening chamber. The steady supply of fresh blood avoids secondary effects by nonphysiological accumulation of activation products. Experiments with three subsequently tested biomaterials showed results similar to literature and our own experience. The reported results suggest that our developed flow model allows the evaluation of blood-contacting materials under physiological flow conditions. By adjusting the occurring wall shear stress, the model can be adapted for selected test conditions.
Fluid dynamics in the human heart: Altered vortex formation and wash-out in mitral regurgitation simulations
Authors: Brenneisen Jochen , Wentzel Carlo , Karwan Farokh , Dössel Olaf , Loewe Axel
Published: December 2021

Mitral regurgitation alters the flow conditions in the left ventricle. To account for quantitative changes and to investigate the behavior of different flow components, a realistic computational model of the whole human heart was employed in this study. While performing fluid dynamics simulations, a scalar transport equation was solved to analyze vortex formation and ventricular wash-out for different regurgitation severities. Additionally, a particle tracking algorithm was implemented to visualize single components of the blood flow. We confirmed a significantly lowered volume of the direct flow component as well as a higher vorticity in the diseased case.
Traditional versus Neural Network Classification Methods for Facial Emotion Recognition
Authors: Arabian Herag , Wagner-Hartl Verena , Moeller Knut
Published: December 2021

Facial emotion recognition (FER) is a topic that has gained interest over the years for its role in bridging the gap between Human and Machine interactions. This study explores the potential of real time FER modelling, to be integrated in a closed loop system, to help in treatment of children suffering from Autism Spectrum Disorder (ASD). The aim of this study is to show the differences between implementing Traditional machine learning and Deep learning approaches for FER modelling. Two classification approaches were taken, the first approach was based on classic machine learning techniques using Histogram of Oriented Gradients (HOG) for feature extraction, with a k-Nearest Neighbor and a Support Vector Machine model as classifiers. The second approach uses Transfer Learning based on the popular “Alex Net” Neural Network architecture. The performance of the approaches was based on the accuracy of randomly selected validation sets after training on random training sets of the Oulu-CASIA database. The data analyzed shows that traditional machine learning methods are as effective as deep neural net models and are a good compromise between accuracy, extracted features, computational speed and costs.
Quantitative assessment of ventricular far field removal techniques for clinical unipolar electrograms
Authors: Lorenz Nick Johannes , Unger Laura Anna , Luik Armin , Dössel Olaf
Published: December 2021

The incidence of atrial tachycardia steadily increases in industrial nations. During invasive electrophysiological studies, a catheter measures electrograms within the atrium to assist detailed diagnosis and treatment planning. With unipolar and bipolar electrograms, two different acquisition modes are clinically available. Unipolar electrograms have several advantages over bipolar electrograms. However, unipolar electrograms are more affected by noise and the ventricular far field. Therefore, only bipolar electrograms are typically used in clinical settings. A recently published ventricular far field removal technique models the ventricular far field by a set of dipoles and yielded promising results in a simulation study. However, the method lacks quantitative clinical validation. Therefore, we adapted the technique to clinical needs and applied it to data sets of two patients using four different lengths of the removal window. Results were compared quantitatively by a tailored residual error measure. The used method resulted in a median reduction of the ventricular far field by approximately 89% using a removal window of optimal length for both patients. The results showed that the dipole method provides an alternative to other VFF removal techniques in clinical practice because it can reveal AA originally hidden by VFF without leading to a prolongation of the electrophysiological study.
Rapid Prototyping of Moulds for PDMS-based Microfluidic Chips
Authors: Schmidt-Speicher Leona M. , Mellert Tobias , Hurtado Rivera Andrea C. , Länge Kerstin , Ahrens Ralf , Guber Andreas E.
Published: December 2021

To shorten the production time for PDMS-moulds by additive manufacturing (AM) several 3D printers have been investigated in comparison to standard micro-milling by producing benchmark structures. These are evaluated regarding their shape accuracy, the transparency of the casted PDMS which is linked to the surface quality of the mould, and the production time until the moulds are ready to use. Even though the additively manufactured moulds showed significantly better surface quality and shorter production time, the necessary shape accuracy for non-square-structures or structures with < 250 μm edge length could not be achieved due to limiting factors like nozzle diameter, size of the digital micromirror device or spot size of the LCD-panel.
How to Support Students in Maximizing their Outcome with Online Cooperation?
Authors: Benninghoff Mark J. , Isfort Peter , Baumann Martin
Published: December 2021

During the last year, student cooperation has shifted to the digital space. Chats, videoconferencing and online collaboration tools replace physical meetings and face-to-face interactions. While many online tools provide sophisticated technologies to share screens and co-edit manuscripts, the support of collaborative thinking, learning and even fooling around is still underdeveloped, but remains a valuable resource. This study traces whether the given level of instruction details influences the collaboration effectiveness among student working groups in a practical course in Biomedical Engineering. Within the semester’s practical course of Introduction into Medicine, participating students were divided into three groups (A, B and C) of each 4 to 6 students and had to collaborate on a clinical case. Groups A received detailed information and rules on online collaboration, B less detailed information and C only basic technical information. Each group was asked to fulfil an additional pre- and post-task before and after the semester’s practical course. These tasks consisted of solving combinatory puzzles based on isolated information bits and hints that were distributed among the group members. The groups differed only in the instructions they received to fulfil the task. During their work phases, all groups were observed. The study was conducted twice with different student cohorts. School grades were assigned representing 1 for the best up to 6 for the worst performance. The following averaged results were found: Groups B received the best grades (average 1,5 for winter term and average 1,6 for summer term). Second best performance was shown by the groups A (average 2,14 for winter term and average 1,75 for summer term) and finally groups C performed worst (average 2.10 for winter term and average 1,85 for summer term). In the taken times to solve the puzzle tasks, groups B showed up to be best in the summer term and groups A in the winter term. In all categories, groups C delivered the worst grades in average. The results of this study support that it is most reasonable to aid student online collaboration by providing detailed instructions or at least a few hints and instruct them to create their own rules for online collaboration. The results further support that the cooperation gets worse without suggesting any rules or instructions and that student age possesses a negligible influence.
Electrical Impedance Tomography might be a Practical Tool to Provide Information about COVID-19 Pneumonia Progression
Authors: Chen Rongqing , Lovas András , Benyó Balázs , Moeller Knut
Published: December 2021

COVID-19 induced acute respiratory distress syndrome (ARDS) could have two different phenotypes, which might have different response and outcome to the traditional ARDS positive end-expiration pressure (PEEP) treatment. The identification of the different phenotypes in terms of the PEEP recruitment can help improve the patients’ outcome. In this contribution we reported a COVID-19 patient with seven-day electrical impedance tomography monitoring. From the conductivity distribution difference image analysis of the data, a clear course developing trend can be observed in addition to the phenotype identification. This case might suggest that EIT can be a practical tool to identify phenotypes and to provide progressive information of COVID-19 pneumonia.
Carotid Sound Signal Artifact Detection based on Discrete Wavelet Transform Decomposition
Authors: Fuentealba Patricio , Salvi Rutuja , Henze Jasmin , Burmann Anja , Boese Axel , Ataide Elmer , Spiller Moritz , Illanes Alfredo , Friebe Michael
Published: December 2021

Auscultation methods allow a non-invasive diagnosis of cardiovascular diseases like atherosclerosis based on blood flow sounds of the carotid arteries. Since this process is highly dependent on the clinician’s experience, it is of great interest to develop automated data processing techniques for objective assessment. We have recently proposed a computerassisted auscultation system that we use to acquire carotid blood flow sounds. In this work, we present an approach for detecting artifacts within the blood flow sound caused by swallowing or coughing events. For this purpose, we first decompose the signal using a discrete wavelet transform (DTW). Then, we compute an energy ratio between the DWT scales associated with the signal information with and without artifacts using a sliding window of 1 s length. Evaluation based on Kruskal-Wallis and Wilcoxon rank-sum tests shows a statistically significant difference (p-value<.0001) between the signal with and without artifact. Therefore, the proposed method allows the identification of the studied signal artifacts.
A multi-purpose phantom kit for magnetic particle imaging
Authors: Löwa Norbert , Hoffmann Rebecca , Gutkelch Dirk , Kosch Olaf , Dutz Silvio , Wiekhorst Frank
Published: December 2021

Phantoms are essential tools for the development and characterization of Magnetic Particle Imaging (MPI), an imaging technique that can quantitatively map the spatial distribution of magnetic nanoparticles (MNP). The objective of this study was to develop and validate a modular MPI phantom kit with high versatility for platform-independent quality assurance and the assembling of defined geometries in MPI. It was shown that the developed MPI phantom kit can be used for both application scenario testing and quality assurance in MPI which provides the basis for future reference phantoms to directly compare existing scanners within the MPI community.
Physical characterization of biomedical magnetic nanoparticles using multi-detector centrifugal field-flow fractionation
Authors: Remmo Amani , Löwa Norbert , Peter Julija , Wiekhorst Frank
Published: December 2021

The unique magnetic properties of magnetic nanoparticles (MNP) combined with their small size already led to numerous medical applications. Accurate determination of their magnetic properties is a key requirement enquired by users, that is impeded by the ever-present distribution of MNP sizes. Field flow fractionation (FFF) techniques may help to overcome these limitations by first separating the particles before characterization. In this study, we demonstrate the use of centrifugal FFF coupled to online detectors for fractionation, structural, and magnetic characterization of MNP. The primary goal is to establish a reproducible centrifugal FFF (CF3) method for MNP fractionation We show that CF3 has the same capability as other FFF techniques in resolving the bimodal hydrodynamic size distribution present in the commercial MNP system Resovist® but is faster and more straightforward through its technical approach.
Twisted string actuation with position feedback for robotic endoscopy
Authors: Schlesiger Davina , Giacoppo Giuliano A. , Schäfer Max B. , Pott Peter P.
Published: December 2021

A twisted string actuator (TSA) is a small, strong, lightweight, and low-cost gear, transforming rotation into a linear pulling movement. The TSA consists of two or more strings that are twisted along their common longitudinal axis. The helix formed in this process becomes shorter the further the bundle is twisted. A possible application is a tendon-based endoscopic robot. To control the movement of the endoscope, a precise contraction of the tendon is necessary. Since the strings of the TSA show an elastic behaviour, position feedback is needed to determine the exact movement of the TSA. In this paper, a TSA with a closed-loop position control by a low-cost displacement sensor is presented.
Nintedanib suppresses expression of extracellular matrix proteins in TGF-β1-stimulated primary human fibroblasts of the Tenon
Authors: Brietzke Andreas , Guthoff Rudolf F. , Grabow Niels , Stahnke Thomas
Published: December 2021

The development of strategies for fibrosis prevention is a perpetual cutting the edge challenge, especially in ophthalmologic fistulating surgery. Stenosis of liquid draining implants but also fibrotic activation of implant-associated tissues are major clinical examples for fibrosis induced implant failure. Implant coating or incorporation of antifibrotic agents offer a promising approach to minimise failure rates. Nintendanib is a drug that has been successfully used for the treatment of ideopathic pulmonary fibrosis since 2015. In this study, we evaluated the suitability of Nintedanib for ophthalmic therapeutic treatment. Therefore, the antifibrotic potential of the active substance was tested with a fibrotic cell culture model on primary fibroblasts of the Tenon (hTF) in vitro. The concentration of 10μM Nintedanib demonstrated a marginal effect on cell viability but coincidently diminished cell proliferation remarkably. Both, immunocytochemical and Western blot analyses revealed a significant inhibitory effect of Nintedanib on the TGF-β1 induced expression of the extracellular matrix (ECM) components fibronectin and collagen. Moreover it supressed the expression and formation of stress fibres of the fibrotic marker protein alpha smooth muscle actin (α-SMA).
Drug-eluting coating of extruded polymeric tubular microstructures
Authors: Sahmel Olga , Siewert Stefan , Bajer Dalibor , Reske Thomas , Arbeiter Daniela , Friederike Kreiner Christine , Guthoff Rudolf , Schmitz Klaus-Peter , Grabow Niels
Published: December 2021

Extrusion is a common manufacturing process for semi-finished polymer products in various biomedical applications. Extrusion enables processing of a wide range of biomaterials, as well as different cross-sectional geometries. Furthermore, feasibility of drug elution, as it is used for a variety of medical devices, for example microstents for minimally invasive glaucoma therapy, was assessed. The current study deals with manufacturing of polymeric microtubes by extrusion processing. Semi-finished products were made of biodegradable poly-L-lactide (PLLA) and a non-biodegradable polycarbonate-based silicone elastomer (SIL) and covered with a polymer/drug combination, with resveratrol as active ingredient. Three different concentrations of polymer/resveratrol were applied by means of spray-coating. The release behavior of active ingredient was analyzed in vitro at 37°C and showed a correlation between the amount of drug and release time. With higher drug content, a faster release was observed. In addition, the release from SIL was faster compared with PLLA.
Investigation of auditory neuronal survival and outgrowth using a cochlear implant in an artificial cochlear model
Authors: Abdoul Tchadarou , Schwieger Jana , Lenarz Thomas , Nogueira Waldo , Scheper Verena
Published: December 2021

Cochlear implants (CI) can restore hearing to people suffering from sensorineural hearing loss. The CI uses an array of electrodes inserted in the scala tympani to stimulate the spiral ganglion neurons (SGN), which are located in the bony axis of the inner ear. The spatial distance between the electrodes and the SGN results in spread of excitation and unfocused stimulation. This distance could be bypassed by a neurite outgrowth towards the CI. In order to establish a culture system for the development of novel strategies for CI optimization, a neurite outgrowth chamber (NOC) allowing clinically relevant electrical stimulation paradigms was developed using fused deposition modelling. It was made out of biocompatible UV-curing silicone. The NOC was equipped with a slot to insert the electrode array into a scala tympani compartment whereas SGN isolated from postnatal rats were cultured in a neighbouring region mimicking the Rosenthal’s canal. Sound delivered through loudspeakers playing a radio program was captured by the CI sound processor, positioned outside the NOC, for 17 hours daily during a four-day period. The NOCs were tightly sealed and the electrode array could be positioned in the scala tympani compartment. The experimental setup allowed cell cultivation and the stimulation resulted in a significantly increased neurite length of around 36% while explant area and neurite number did not differ to the negative control (NC). A new in vitro testing system which considers the anatomy of the cochlea and clinic stimulation conditions has been developed and validated. The validation experiments resulted in increased neurite length. This indicates a progress in bridging the anatomical gap between electrode and stimulated neurons.
In vitro release of chlorhexidine from UV-cured PEGDA drug delivery scaffolds
Authors: Rekowska Natalia , Riess Alexander , Mau Robert , Eickner Thomas , Seitz Hermann , Grabow Niels , Teske Michael
Published: December 2021

Drug delivery systems (DDS) are suitable for controlled local drug release in order to ensure safety and effectiveness of medical treatment. The choice and characterization of biomaterials that can be used as a DDS is a challenging step in the administration of drugs. Novel 3D printing photopolymerization-based techniques create the possibility for designing individual, patient-tailored DDS. Poly(ethylene glycol) diacrylate`s (PEGDA`s) chemical and biological properties make it a suitable photopolymerisable resin for the creation of DDS. This study describes the in vitro release of the antiseptic drug chlorhexidine (CHX) from UV-cured PEGDA and its copolymers (butanediol diacrylate, pentaerythritol triacrylate and pentaerythritol tetraacrylate) samples. A substantial decrease in CHX release with increasing concentration of the copolymers in comparison to pure PEGDA was obtained only for butanediol diacrylate. For pentaerythritol triacrylate and pentaerythritol tetraacrylate only a tendency of decreased CHX release with increasing concentration was detected. Therefore, release profiles of the low molecular drug CHX from PEGDA samples could be modified by the addition of copolymers with a different number of acrylate groups and PEGDA can be considered as a promising candidate for the preparation of novel DDS.
Pandemic Robot
Authors: Bauer Jochen , Dengler Simon , Faubel Leoni , Franke Jörg , Ristok Bruno , Struck Matthias , Frischholz Robert , Wittenberg Thomas
Published: December 2021

Robot-based service platforms are currently establishing themselves as new and affordable variants for supporting care in elderly, retirement and nursing homes. Many are open multifunctional platforms, which can potentially be integrated into such environments, if the necessary infrastructure is available. Furthermore, many services can be realized on these platforms, which can be used to foster distant interactions between inhabitants and care-providers, while simultaneously keeping up the quality of life of the inhabitants. Open mobile robotic platforms allow the extension with adequate new sensors. To detect infectious diseases of residents and healthcare-professionals, optical sensors can be used for the assessment of vital data such as heartrate and heartrate variability, respiratory rate, SpO2 or temperature. Additionally, you can consider demographic data (age, gender, constitution) of the observed person for the optical assessment, i.e. obtained by facial image analysis. As these mobile platforms are also equipped for telepresence, in case of detecting an infected person, these systems support video conferencing with their built-in cameras and microphones. Finally, the interaction with the electronic care record is necessary to upload all acquired vital data and further relevant information. All the named technologies have been under investigation in the past years and are currently moving from laboratory settings to real-world scenarios. Nevertheless, the smooth integration of all components into one system architecture in combination with (AI-based) data analysis are still open issues.
Paravalvular leakage of transcatheter aortic valve replacements depending on aortic annulus calcification
Authors: Kaule Sebastian , Oener Alper , Grabow Niels , Schmitz Klaus-Peter , Siewert Stefan , Stiehm Michael
Published: December 2021

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.
Polymer selection for Eustachian tube stent application based on mechanical, thermal and degradation behavior
Authors: Lebahn Kerstin , Stöffler Kerstin , Oschatz Stefan , Arbeiter Daniela , Reske Thomas , Schmitz Klaus-Peter , Paasche Gerrit , Lenarz Thomas , Grabow Niels
Published: December 2021

The novel concept of stenting the Eustachian tube was established to provide an effective and safe therapy of Eustachian tube dysfunction. Biodegradable polymer stents are being developed to restore impaired tube function. As the supporting effect may be required for different time periods, PLA-co-PEG copolymers, PLLGA, PDLLA and PDS, having shorter degradation times compared to PLLA, were evaluated as potential stent materials. Since tensile tests and thermal analyses of solvent cast films from PLA-co-PEG copolymers showed comparable properties to PLLA, stent samples were manufactured from these materials. Mechanical stent testing revealed an increase of elastic recoil and slight decrease of collapse pressure compared to PLLA. In a short term accelerated degradation study a considerable percentage molar mass reduction and an increasing degree of crystallinity depending on PEG content was found. Based on the results obtained, the tested polymers offer a promising, faster degradable alternative to the established stent material PLLA.
Thermal welding of polymeric biomaterials: Development of a novel device for temperature controlled local application
Authors: Tautorat Carsten , Lebahn Kerstin , Oschatz Stefan , Arbeiter Daniela , Schmitz Klaus-Peter , Grabow Niels , Schmidt Wolfram
Published: December 2021

We present a thermal processing device, equipped for local heating and welding of biomaterials, e.g. electrospun nonwovens or polymer films. Depending on the application and choice of materials, we aim to determine appropriate processing parameters for permanent and non-permanent welds. Due to the modular device structure, applicationspecific heating tools can be used. Process temperature up to 250 °C is feasible.

In this concept study, a welding tool with interchangeable small-size heating tips of different geometric shapes were investigated regarding their suitability for welding of polycarbonate urethane based silicone elastomer nonwovens. Generated welds were examined by imaging techniques and tensile testing. Regardless of the tip shape, welds were generated withstanding forces up to 3.0 N and 4.3 N for tensile and shear loading, respectively.
A hydrogel based quasi-stationary test system for in vitro dexamethasone release studies for middle ear drug delivery systems
Authors: Eickner Thomas , Teske Michael , Rekowska Natalia , Senz Volkmar , Schmitz Klaus-Peter , Grabow Niels
Published: December 2021

For the investigation of in vitro drug release, methods have been used in which samples of drug delivery systems are immersed in release medium. The medium is used to measure drug concentration via chromatography or photometry. These systems are suitable to investigate the drug release of different systems or to simulate tissue environments. When considering predominantly humid regions, e.g. for drug release into the cochlea through the round window membrane by a drug delivery system placed at that membrane, reproducible in vitro determination of drug release becomes particularly challenging. In this study the development of a system is reported that allows the investigation of the in vitro drug release simulating such conditions.

The presented test system consists of an alginate hydrogel in glass vials simulating the biological membrane, which separates the drug delivery system from the medium filled compartment. Saline is used as release medium and injected under the hydrogel. The samples are placed on top of the hydrogel, which slightly contacts the medium surface. The drug concentration in the release medium was determined by HPLC measurements.

This system allows for testing the release of dexamethasone without the samples being completely surrounded by medium. The hydrogel mediates the diffusion of the drug by ensuring the contact with the medium. Release was monitored for more than 23 days. The presented concept was successfully designed and manufactured. The system is inexpensive and can be duplicated easily. In this study, it was used to monitor the drug release of dexamethasone from PEGDA700 derived polymer. One challenge that remains to be considered is the low mechanical stability of the hydrogel, which results in a need for repeated manufacturing during the handling of the system.
Estimation of calendar age based on autonomic cardiovascular function by applying machine learning techniques
Authors: Sabeghi Rassoul , Bär Karl-Jürgen , Schumann Andy
Published: December 2021

Aging is accompanied by changes in the cardiovascular physiology that promote the development of age-related diseases. This paper presents a modern approach to quantify the physiological effects of age on the cardiovascular system by applying modern machine learning techniques to several indicators of autonomic cardiovascular function. In 885 healthy subjects, 33 different indices were calculated on resting state electrocardiogram and continuous blood pressure recordings. Based on those parameters, five different approaches were applied in order to reconstruct the calendar age of healthy subjects, i.e., linear regression (LR), neural network (NN), Gaussian process regression (GPR), support vector regression (SVR), and relevance vector regression (RVR). Hyper parameters of machine learning methods were optimized via grid search. After 20 repetitions of a five-fold cross-validation, the mean absolute error (MAE) was computed between the calendar and estimated age to assess the accuracy of each method. The results show that the lowest error for age estimation was achieved using SVR with a MAE of 5.49 years. GPR performed comparably well to SVR with a MAE of 5.55 years, while NN led to a MAE of 5.72 years. RVR and LR revealed MAE of more than six years (6.21 and 6.34 years). The error of age estimation could be further reduced by applying outlier correction to the input data leading to a minimum MAE of 4.53 years with GPR. In conclusion, our results suggest that machine learning can be used to quantify the effects of healthy aging on cardio-vascular function.
Validation of Finite Element Analysis of a selfexpanding polymeric microstent for treatment of Fallopian tube occlusions
Authors: Dierke Ariane , Kuske Thomas , Frank Hagen , Bohne Eric , Brandt-Wunderlich Christoph , Knorre Luise , Stiehm Michael , Bock Andrea , Grabow Niels , Wree Andreas , Zygmunt Marek , Schmitz Klaus-Peter , Siewert Stefan
Published: December 2021

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.
Method to determine particle release during long-term loading for assessment of coating durability of cardiovascular stents
Authors: Schmidt Wolfram , Brandt-Wunderlich Christoph , Kurzhals Anja , Schmitz Klaus-Peter , Grabow Niels
Published: December 2021

Many catheters and vascular implants are coated to increase biocompatibility or to reduce friction during catheter based implantation. Several regulations require assessment of coating durability over the implant’s life time. An in vitro method for stent testing is presented to measure released particulate matter at defined inspection intervals. The method was validated using polystyrene microspheres with a size of 10, 25 and 50 μm to check for particle recovery (n=6). Two cleaning steps followed. Particle counting was performed by light obscuration method. The recovery rate was 103±5% (10μm), 94±4% (25 μm) and 78±12% (50 μm), respectively, meeting the requirements of FDA guidance documents (i.e. FDA 1545). Less than 3% of the particles were found in the cleaning solutions. The method using a fixed volume during stent loading can be adapted to all durability testers where tubes are used to fix the stents (radial pulsatile, bending, axial compression, torsion).