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Background
The actual task of electrocardiographic examinations is to increase the reliability of diagnosing the condition of the heart. Within the framework of this task, an important direction is the solution of the inverse problem of electrocardiography, based on the processing of electrocardiographic signals of multichannel cardio leads at known electrode coordinates in these leads (Titomir et al. Noninvasiv electrocardiotopography, 2003), (Macfarlane et al. Comprehensive Electrocardiology, 2nd ed. (Chapter 9), 2011).
Results
In order to obtain more detailed information about the electrical activity of the heart, we carry out a reconstruction of the distribution of equivalent electrical sources on the heart surface. In this area, we hold reconstruction of the equivalent sources during the cardiac cycle at relatively low hardware cost. ECG maps of electrical potentials on the surface of the torso (TSPM) and electrical sources on the surface of the heart (HSSM) were studied for different times of the cardiac cycle. We carried out a visual and quantitative comparison of these maps in the presence of pathological regions of different localization. For this purpose we used the model of the heart electrical activity, based on cellular automata.
Conclusions
The model of cellular automata allows us to consider the processes of heart excitation in the presence of pathological regions of various sizes and localization. It is shown, that changes in the distribution of electrical sources on the surface of the epicardium in the presence of pathological areas with disturbances in the conduction of heart excitation are much more noticeable than changes in ECG maps on the torso surface.
Purpose
Computerized medical imaging processing assists neurosurgeons to localize tumours precisely. It plays a key role in recent image-guided neurosurgery. Hence, we developed a new open-source toolkit, namely Slicer-DeepSeg, for efficient and automatic brain tumour segmentation based on deep learning methodologies for aiding clinical brain research.
Methods
Our developed toolkit consists of three main components. First, Slicer-DeepSeg extends the 3D Slicer application and thus provides support for multiple data input/ output data formats and 3D visualization libraries. Second, Slicer core modules offer powerful image processing and analysis utilities. Third, the Slicer-DeepSeg extension provides a customized GUI for brain tumour segmentation using deep learning-based methods.
Results
The developed Slicer-DeepSeg was validated using a public dataset of high-grade glioma patients. The results showed that our proposed platform’s performance considerably outperforms other 3D Slicer cloud-based approaches.
Conclusions
Developed Slicer-DeepSeg allows the development of novel AI-assisted medical applications in neurosurgery. Moreover, it can enhance the outcomes of computer-aided diagnosis of brain tumours. Open-source Slicer-DeepSeg is available at github.com/razeineldin/Slicer-DeepSeg.
Intraoperative imaging can assist neurosurgeons to define brain tumours and other surrounding brain structures. Interventional ultrasound (iUS) is a convenient modality with fast scan times. However, iUS data may suffer from noise and artefacts which limit their interpretation during brain surgery. In this work, we use two deep learning networks, namely UNet and TransUNet, to make automatic and accurate segmentation of the brain tumour in iUS data. Experiments were conducted on a dataset of 27 iUS volumes. The outcomes show that using a transformer with UNet is advantageous providing an efficient segmentation modelling long-range dependencies between each iUS image. In particular, the enhanced TransUNet was able to predict cavity segmentation in iUS data with an inference rate of more than 125 FPS. These promising results suggest that deep learning networks can be successfully deployed to assist neurosurgeons in the operating room.
In vitro, hydrogel-based ECMs for functionalizing surfaces of various material have played an essential role in mimicking native tissue matrix. Polydimethylsiloxane (PDMS) is widely used to build microfluidic or organ-on-chip devices compatible with cells due to its easy handling in cast replication. Despite such advantages, the limitation of PDMS is its hydrophobic surface property. To improve wettability of PDMS-based devices, alginate, a naturally derived polysaccharide, was covalently bound to the PDMS surface. This alginate then crosslinked further hydrogel onto the PDMS surface in desired layer thickness. Hydrogel-modified PDMS was used for coating a topography chip system and in vitro investigation of cell growth on the surfaces. Moreover, such hydrophilic hydrogel-coated PDMS is utilized in a microfluidic device to prevent unspecific absorption of organic solutions. Hence, in both exemplary studies, PDMS surface properties were modified leading to improved devices.
The coculture of osteogenic and angiogenic cells and the resulting paracrine signaling via soluble factors are supposed to be crucial for successfully engineering vascularized bone tissue equivalents. In this study, a coculture system combining primary human adiposederived stem cells (hASCs) and primary human dermal microvascular endothelial cells (HDMECs) within two types of hydrogels based on methacryloyl‐modified gelatin (GM) as three‐dimensional scaffolds was examined for its support of tissue specific cell functions. HDMECs, together with hASCs as supporting cells, were encapsulated in soft GM gels and were indirectly cocultured with hASCs encapsulated in stiffer GM hydrogels additionally containing methacrylate‐modified hyaluronic acid and hydroxyapatite particles. After 14 days, the hASC in the stiffer gels (constituting the “bone gels”) expressed matrix proteins like collagen type I and fibronectin, as well as bone‐specific proteins osteopontin and alkaline phosphatase. After 14 days of coculture with HDMEC‐laden hydrogels, the viscoelastic properties of the bone gels were significantly higher compared with the gels in monoculture. Within the soft vascularization gels, the formed capillary‐like networks were significantly longer after 14 days of coculture than the structures in the control gels. In addition, the stability as well as the complexity of the vascular networks was significantly increased by coculture. We discussed and concluded that osteogenic and angiogenic signals from the culture media as well as from cocultured cell types, and tissue‐specific hydrogel composition all contribute to stimulate the interplay between osteogenesis and angiogenesis in vitro and are a basis for engineering vascularized bone.
Though bioprinting is a forward-looking approach in bone tissue engineering, the development of bioinks which are on the one hand processable with the chosen printing technique, and on the other hand possess the relevant mechanical as well as osteoconductive features remains a challenge. In the present study, polymer solutions based on methacrylated gelatin and methacrylated hyaluronic acid modified with hydroxyapatite (HAp) particles (5 wt%) were prepared. Encapsulation of primary human adipose derived stem cells in the HAp-containing gels and culture for 28 d resulted in a storage moduli significantly increased to 126% ± 9.6% compared to the value on day 1 by the sole influence of the HAp. Additional use of osteogenic media components resulted in an increase of storage module up to 199% ± 27.8%. Similarly, the loss moduli was increased to 370% ± 122.1% under the influence of osteogenic media components and HAp. Those changes in rheological material characteristics indicate a distinct change in elastic and viscous hydrogel properties, and are attributed to extensive matrix production in the hydrogels by the encapsulated cells, what could also be proven by staining of bone matrix components like collagen I, fibronectin, alkaline phosphatase and osteopontin. When using the cell-laden polymer solutions as bioinks to build up relevant geometries, the ink showed excellent printability and the printed grid structure's integrity remained intact over a culture time of 28 d. Again, an intense matrix formation as well as upregulation of osteogenic markers by the encapsulated cells could be shown. In conclusion, we demonstrated that our HAp-containing bioinks and hydrogels on basis of methacrylated gelatin and hyaluronic acid are on the one hand highly suitable for the build up of relevant three-dimensional geometries with microextrusion bioprinting, and on the other hand exhibit a significant positive effect on bone matrix development and remodeling in the hydrogels, as indicated by rheological measurements and staining of bone components. This makes the developed composite hydrogels an excellent material for bone bioprinting approaches.
The incudo-malleal joint (IMJ) in the human middle ear is a true diarthrodial joint and it has been known that the flexibility of this joint does not contribute to better middle-ear sound transmission. Previous studies have proposed that a gliding motion between the malleus and the incus at this joint prevents the transmission of large displacements of the malleus to the incus and stapes and thus contributes to the protection of the inner ear as an immediate response against large static pressure changes. However, dynamic behavior of this joint under static pressure changes has not been fully revealed. In this study, effects of the flexibility of the IMJ on middle-ear sound transmission under static pressure difference between the middle-ear cavity and the environment were investigated. Experiments were performed in human cadaveric temporal bones with static pressures in the range of +/- 2 kPa being applied to the ear canal (relative to middle-ear cavity). Vibrational motions of the umbo and the stapes footplate center in response to acoustic stimulation (0.2-8 kHz) were measured using a 3D-Laser Doppler vibrometer for (1) the natural IMJ and (2) the IMJ with experimentally-reduced flexibility. With the natural condition of the IMJ, vibrations of the umbo and the stapes footplate center under static pressure loads were attenuated at low frequencies below the middle-ear resonance frequency as observed in previous studies. After the flexibility of the IMJ was reduced, additional attenuations of vibrational motion were observed for the umbo under positive static pressures in the ear canal (EC) and the stapes footplate center under both positive and negative static EC pressures. The additional attenuation of vibration reached 4~7 dB for the umbo under positive static EC pressures and the stapes footplate center under negative EC pressures, and 7~11 dB for the stapes footplate center under positive EC pressures. The results of this study indicate an adaptive mechanism of the flexible IMJ in the human middle ear to changes of static EC pressure by reducing the attenuation of the middle-ear sound transmission. Such results are expected to be used for diagnosis of the IMJ stiffening and to be applied to design of middle-ear prostheses.
In vitro models of human adipose tissue may serve as beneficial alternatives to animal models to study basic biological processes, identify new drug targets, and as soft tissue implants. With this approach, we aimed to evaluate adipose-derived stem cells (ASC) and mature adipocytes (MA) comparatively for the application in the in vitro setup of adipose tissue constructs to imitate native adipose tissue physiology. We used human primary MAs and human ASCs, differentiated for 14 days, and encapsulated them in collagen type I hydrogels to build up a three-dimensional (3D) adipose tissue model. The maintenance of the models was analyzed after seven days based on a viability staining. Further, the expression of the adipocyte specific protein perilipin A and the release of leptin and glycerol were evaluated. Gene transcription profiles of models based on dASCs and MAs were analyzed with regard to native adipose tissue. Compared to MAs, dASCs showed an immature differentiation state. Further, gene transcription of MAs suggests a behavior closer to native tissue in terms of angiogenesis, which supports MAs as preferred cell type. In contrast to native adipose tissue, genes of de novo lipogenesis and tissue remodeling were upregulated in the in vitro attempts.
In vitro composed vascularized adipose tissue is and will continue to be in great demand e.g. for the treatment of extensive high-graded burns or the replacement of tissue after tumor removal. Up to date, the lack of adequate culture conditions, mainly a culture medium, decelerates further achievements. In our study, we evaluated the influence of epidermal growth factor (EGF) and hydrocortisone (HC), often supplemented in endothelial cell (EC) specific media, on the co-culture of adipogenic differentiated adipose derived stem cells (ASCs) and microvascular endothelial cells (mvECs). In ASCs, EGF and HC are thought to inhibit adipogenic differentiation and have lipolytic activities. Our results showed that in indirect co-culture for 14 days, adipogenic differentiated ASCs further incorporated lipids and partly gained an univacuolar morphology when kept in media with low levels of EGF and HC. In media with high EGF and HC levels, cells did not incorporate further lipids, on the contrary, cells without lipid droplets appeared. Glycerol release, to measure lipolysis, also increased with elevated amounts of EGF and HC in the culture medium. Adipogenic differentiated ASCs were able to release leptin in all setups. MvECs were functional and expressed the cell specific markers, CD31 and von Willebrand factor (vWF), independent of the EGF and HC content as long as further EC specific factors were present. Taken together, our study demonstrates that adipogenic differentiated ASCs can be successfully co-cultured with mvECs in a culture medium containing low or no amounts of EGF and HC, as long as further endothelial cell and adipocyte specific factors are available.
The development of in vitro adipose tissue constructs is highly desired to cope with the increased demand for substitutes to replace damaged soft tissue after high graded burns, deformities or tumor removal. To achieve clinically relevant dimensions, vascularization of soft tissue constructs becomes inevitable but still poses a challenge. Adipose-derived stem cells (ASCs) represent a promising cell source for the setup of vascularized fatty tissue constructs as they can be differentiated into adipocytes and endothelial cells in vitro and are thereby available in sufficiently high cell numbers.
This review summarizes the currently known characteristics of ASCs and achievements in adipogenic and endothelial differentiation in vitro. Further, the interdependency of adipogenesis and angiogenesis based on the crosstalk of endothelial cells, stem cells and adipocytes is addressed at the molecular level. Finally, achievements and limitations of current co-culture conditions for the construction of vascularized adipose tissue are evaluated.
Artificial adipose tissue (AT) constructs are urgently needed to treat severe wounds, to replace removed tissue, or for the use as in vitro model to screen for potential drugs or study metabolic pathways. The clinical translation of products is mostly prevented by the absence of a vascular component that would allow a sustainable maintenance and an extension of the construct to a relevant size. With this study, we aimed to evaluate the suitability of a novel material based on bacterial cellulose (CBM) on the defined adipogenic differentiation of human adipose-derived stem cells (ASCs) and the maintenance of the received adipocytes (diffASCs) and human microvascular endothelial cells (mvECs) in mono- and coculture. A slight acceleration of adipogenic differentiation over regular tissue culture polystyrene (TCPS) was seen on CBM under defined conditions, whereas on the maintenance of the generated adipocytes, comparable effects were detected for both materials. CBM facilitated the formation of vascular like structures in monoculture of mvECs, which was not observed on TCPS. By contrast, vascular-like structures were detected in CBM and TCPS in coculture by the presence of diffASCs. Concluding, CBM represents a promising material in vascularized AT engineering with the potential to speed up and simplify the in vitro setup of engineered products.
Human bestrophin-1 protein (hBest1) is a transmembrane channel associated with the calcium-dependent transport of chloride ions in the retinal pigment epithelium as well as with the transport of glutamate and GABA in nerve cells. Interactions between hBest1, sphingomyelins, phosphatidylcholines and cholesterol are crucial for hBest1 association with cell membrane domains and its biological functions. As cholesterol plays a key role in the formation of lipid rafts, motional ordering of lipids and modeling/remodeling of the lateral membrane structure, we examined the effect of different cholesterol concentrations on the surface tension of hBest1/POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and hBest1/SM Langmuir monolayers in the presence/absence of Ca2+ ions using surface pressure measurements and Brewster angle microscopy studies. Here, we report that cholesterol: (1) has negligible condensing effect on pure hBest1 monolayers detected mainly in the presence of Ca2+ ions, and; (2) induces a condensing effect on composite hBest1/POPC and hBest1/SM monolayers. These results offer evidence for the significance of intermolecular protein–lipid interactions for the conformational dynamics of hBest1 and its biological functions as multimeric ion channel.
The data present in this article affords insides in the characterization of a newly described bi-functional furan-melamine monomer, which is used for the production of monodisperse, furan-functionalized melamine formaldehyde particles. In the related research article Urdl et al., 2019 data interpretations can be found. The furan functionalization of particles is necessary to perform reversible Diels-Alder reactions with maleimide (BMI) crosslinker to form thermoreversible network systems. To understand the reaction conditions of Diels Alder (DA) reaction with a Fu-Mel monomer and a maleimide crosslinker, model DA reaction were performed and evaluated using dynamic FT-IR measurements. During retro Diels-Alder (rDA) reactions of the monomer system, it was found out that some side reaction occurred at elevated temperatures. The data of evaluating the side reaction is described in one part of this manuscript. Additional high resolution SEM images of Fu Mel particles are shown and thermoreversible particle networks with BMI2 are shown. The data of different Fu-Mel particle networks with maleimide crosslinker are presented. Therefore, the used maleimide crosslinker with different spacer lengths were synthesized and the resulting networks were analyzed by ATR-FT-IR, SEM and DSC.
The data presented in this article characterize the thermomechanical and microhardness properties of a novel melamine-formaldehyde resin (MF) intended for the use as a self-healing surface coating. The investigated MF resin is able to undergo reversible crosslinking via Diels Alder reactive groups. The microhardness data were obtained from nanoindentation measurements performed on solid resin film samples at different stages of the self-healing cycle. Thermomechanical analysis was performed under dynamic load conditions. The data provide supplemental material to the manuscript published by Urdl et al. 2020 (https://doi.org/10.1016/j.eurpolymj.2020.109601) on the self-healing performance of this resin, where a more thorough discussion on the preparation, the properties of this coating material and its application in impregnated paper-based decorative laminates can be found.
The paper describes how eye-tracking can be used to explore electronic patient records (EPR) in a sterile environment. As an information display, we used a system that we developed for the presentation of patient data and for supporting surgical hand disinfection. The eye-tracking was performed using the Tobii Eye Tracker 4C, and the connection between the eye-tracker and the HTML website was realized using the Tobii EyeX Chrome Extension. Interactions with the EPR are triggered by fixations of icons. The interaction was working as intended, but test persons reported a high mental load while using the system.
The interaction between lipid bilayers in water has been intensively studied over the last decades. Osmotic stress was applied to evaluate the forces between two approaching lipid bilayers in aqueous solution. The force–distance relation between lipid mono- or bilayers deposited on mica sheets using a surface force apparatus (SFA) was also measured. Lipid stabilised foam films offer another possibility to study the interactions between lipid monolayers. These films can be prepared comparatively easy with very good reproducibility. Foam films consist usually of two adsorbed surfactant monolayers separated by a layer of the aqueous solution from which the film is created. Their thickness can be conveniently measured using microinterferometric techniques. Studies with foam films deliver valuable information on the interactions between lipid membranes and especially their stability and permeability. Presenting inverse black lipid membrane (BLM) foam films supply information about the properties of the lipid self-organisation in bilayers. The present paper summarises results on microscopic lipid stabilised foam films by measuring their thickness and contact angle. Most of the presented results concern foam films prepared from dispersions of the zwitterionic lipid 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and some of its mixtures with the anionic lipid — 1,2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DMPG).
The strength of the long range and short range forces between the lipid layers is discussed. The van der Waals attractive force is calculated. The electrostatic repulsive force is estimated from experiments at different electrolyte concentrations (NaCl, CaCl2) or by modification of the electrostatic double layer surface potential by incorporating charged lipids in the lipid monolayers. The short range interactions are studied and modified by using small carbohydrates (fructose and sucrose), ethanol (EtOH) or dimethylsulfoxide (DMSO). Some results are compared with the structure of lipid monolayers deposited at the liquid/air interface (monolayers spread in Langmuir trough), which are one of most studied biomembrane model system. The comparison between the film thickness and the free energy of film formation is used to estimate the contribution of the different components of the disjoining pressure to the total interaction in the film and their dependence on the composition of the film forming solution.
Properties data of phenolic resins synthetized for the impregnation of saturating Kraft paper
(2018)
The quality of decorative laminates boards depends on the impregnation process of Kraft papers with a phenolic resin,which constitute the raw materials for the manufacture of the cores of such boards.In the laminates industries,the properties of resins are adapted via their syntheses,usually by mixing phenol and formaldehyde in a batch,where additives,temperature and stirring parameters can be controlled. Therefore, many possibilities of preparation and phenolic resins exist, that leads to different combinations of physico chemical properties. In this article, the properties data of eight phenolic resins synthetized with different parameters of pH and reaction times at 60 °C and 90 °C are presented: the losses of pH after synthesis and the dynamic viscosities measured after synthesis and one the solid content is adjusted to 45%w/w in methanol. Data aquired by Differential Scanning Calorimetry (DSC) of the resins and Inverse Gas Chromatography (IGC) of cured solids are given as well.
Analysis of multicellular patterns is required to understand tissue organizational processes. By using a multi-scale object oriented image processing method, the spatial information of cells can be extracted automatically. Instead of manual segmentation or indirect measurements, such as general distribution of contrast or flow, the orientation and distribution of individual cells is extracted for quantitative analysis. Relevant objects are identified by feature queries and no low-level knowledge of image processing is required.
Neurodegenerative disorders (NDDs) are complex, multifactorial disorders with significant social and economic impact in today’s society. NDDs are predicted to become the second-most common cause of death in the next few decades due to an increase in life expectancy but also to a lack of early diagnosis and mainly symptomatic treatment. Despite recent advances in diagnostic and therapeutic methods, there are yet no reliable biomarkers identifying the complex pathways contributing to these pathologies. The development of new approaches for early diagnosis and new therapies, together with the identification of non-invasive and more cost-effective diagnostic biomarkers, is one of the main trends in NDD biomedical research. Here we summarize data on peripheral biomarkers, biofluids (cerebrospinal fluid and blood plasma), and peripheral blood cells (platelets (PLTs) and red blood cells (RBCs)), reported so far for the three most common NDDs—Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). PLTs and RBCs, beyond their primary physiological functions, are increasingly recognized as valuable sources of biomarkers for NDDs. Special attention is given to the morphological and nanomechanical signatures of PLTs and RBCs as biophysical markers for the three pathologies. Modifications of the surface nanostructure and morphometric and nanomechanical signatures of PLTs and RBCs from patients with AD, PD, and ALS have been revealed by atomic force microscopy (AFM). AFM is currently experiencing rapid and widespread adoption in biomedicine and clinical medicine, in particular for early diagnostics of various medical conditions. AFM is a unique instrument without an analog, allowing the generation of three-dimensional cell images with extremely high spatial resolution at near-atomic scale, which are complemented by insights into the mechanical properties of cells and subcellular structures. Data demonstrate that AFM can distinguish between the three pathologies and the normal, healthy state. The specific PLT and RBC signatures can serve as biomarkers in combination with the currently used diagnostic tools. We highlight the strong correlation of the morphological and nanomechanical signatures between RBCs and PLTs in PD, ALS, and AD.
Thin radio-frequency magnetron sputter deposited nano-hydroxyapatite (HA) films were prepared on the surface of a Fe-tricalcium phosphate (Fe-TCP) bioceramic composite, which was obtained using a conventional powder injection moulding technique. The obtained nano-hydroxyapatite coated Fe-TCP biocomposites (nano HA-Fe-TCP) were studied with respect to their chemical and phase composition, surface morphology, water contact angle, surface free energy and hysteresis. The deposition process resulted in a homogeneous, single-phase HA coating. The ability of the surface to support adhesion and the proliferation of human mesenchymal stem cells (hMSCs) was studied using biological short-term tests in vitro. The surface of the uncoated Fe-TCP bioceramic composite showed an initial cell attachment after 24 h of seeding, but adhesion, proliferation and growth did not persist during 14 days of culture.However, the HA-Fe-TCP surfaces allowed cell adhesion, and proliferation during 14 days. The deposition of the nano-HA films on the Fe-TCP surface resulted in higher surface energy, improved hydrophilicity and biocompatibility compared with the surface of the uncoated Fe-TCP. Furthermore, it is suggested that an increase in the polar component of the surface energy was responsible for the enhanced cell adhesion and proliferation in the case of the nano-HA Fe-TCP biocomposites.
Morphometry and stiffness of red blood cells - signatures of neurodegenerative diseases and aging
(2022)
Human red blood cells (RBCs) are unique cells with the remarkable ability to deform, which is crucial for their oxygen transport function, and which can be significantly altered under pathophysiological conditions. Here we performed ultrastructural analysis of RBCs as a peripheral cell model, looking for specific signatures of the neurodegenerative pathologies (NDDs) - Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), utilizing atomic force (AFM) and conventional optical (OM) microscopy. We found significant differences in the morphology and stiffness of RBCs isolated from patients with the selected NDDs and those from healthy individuals. Neurodegenerative pathologies’ RBCs are characterized by a reduced abundance of biconcave discoid shape, lower surface roughness and a higher Young’s modulus, compared to healthy cells. Although reduced, the biconcave is still the predominant shape in ALS and AD cells, while the morphology of PD is dominated by crenate cells. The features of RBCs underwent a marked aging-induced transformation, which followed different aging pathways for NDDs and normal healthy states. It was found that the diameter, height and volume of the different cell shape types have different values for NDDs and healthy cells. Common and specific morphological signatures of the NDDs were identified.
The detection and characterisation of oxide layers on metallic copper samples plays an important role for power electronic modules in the automotive industry. However, since precise identification of oxide layers by visual inspection is difficult and time consuming due to inhomogeneous colour distribution, a reliable and efficient method for estimating their thickness is needed. In this study, hyperspectral imaging in the visible wavelength range (425–725 nm) is proposed as an in-line inspection method for analysing oxide layers in real-time during processing of copper components such as printed circuit boards in the automotive industry. For implementation in the production line a partial least square regression (PLSR) model was developed with a calibration set of n = 12 with about 13,000 spectra per sample to determine the oxide layer thickness on top of the technical copper surfaces. The model shows a good prediction performance in the range of 0–30 nm compared to Auger electron spectroscopy depth profiles as a reference method. The root mean square error (RMSE) is 1.75 nm for calibration and 2.70 nm for full cross validation. Applied to an external dataset of four new samples with about 13,000 spectra per sample the model provides an RMSE of 1.84 nm for prediction and demonstrates the robustness of the model during real-time processing. The results of this study prove the ability and usefulness of the proposed method to estimate the thickness of oxide layers on technical copper. Hence, the application of hyperspectral imaging for the industrial process control of electronic devices is very promising.
Positively charged metallic oxides prevent blood coagulation whereas negatively charged metallic oxides are thrombogenic. This study was performed to examine whether this effect extends to metallic oxide nanoparticles. Oscillation shear rheometry was used to study the effect of zinc oxide and silicon dioxide nanoparticles on thrombus formation in human whole blood. Our data show that oscillation shear rheometry is a sensitive and robust technique to analyze thrombogenicity induced by nanoparticles. Blood without previous contact with nanoparticles had a clotting time (CT) of 16.7 ± 1.0 min reaching a maximal clot strength (CS) of 16 ± 14 Pa (G') after 30 min. ZnO nanoparticles (diameter 70 nm, +37 mV zeta-potential) at a concentration of 1 mg/mL prolonged CT to 20.8 ± 3.6 min and provoked a weak clot (CS 1.5 ± 1.0 Pa). However, at a lower concentration of 100 µg/mL the ZnO particles dramatically reduced CT to 6.0 ± 0.5 min and increased CS to 171 ± 63 Pa. This procoagulant effect decreased at lower concentrations reaching the detection limit at 10 ng/mL. SiO2 nanoparticles (diameter 232 nm, −28 mV zeta-potential) at high concentrations (1 mg/mL) reduced CT (2.1 ± 0.2 min) and stimulated CS (249 ± 59 Pa). Similar to ZnO particles, this procoagulant effect reached a detection limit at 10 ng/mL. Nanoparticles in high concentrations reproduce the surface charge effects on blood coagulation previously observed with large particles or solid metal oxides. However, nanoparticles with different surface charges equally well stimulate coagulation at lower concentrations. This stimulation may be an effect which is not directly related to the surface charge.
Hybrid organic/inorganic nanocomposites combine the distinct properties of the organic polymer and the inorganic filler, resulting in overall improved system properties. Monodisperse porous hybrid beads consisting of tetraethylene pentamine functionalized poly(glycidyl methacrylateco-ethylene glycol dimethacrylate) particles and silica nanoparticles (SNPs) were synthesized under Stoeber sol-gel process conditions. A wide range of hybrid organic/silica nanocomposite materials with different material properties was generated. The effects of n(H2O)/n(TEOS) and c(NH3 ) on the hybrid bead properties particle size, SiO2 content, median pore size, specific surface area, pore volume and size of the SNPs were studied. Quantitative models with a high robustness and predictive power were established using a statistical and systematic approach based on response surface methodology. It was shown that the material properties depend in a complex way on the process factor settings and exhibit non-linear behaviors as well as partly synergistic interactions between the process factors. Thus, the silica content, median pore size, specific surface area, pore volume and size of the SNPs are non-linearly dependent on the water-to-precursor ratio. This is attributed to the effect of the water-to-precursor ratio on the hydrolysis and condensation rates of TEOS. A possible mechanism of SNP incorporation into the porous polymer network is discussed.
Introduction
Despite its high accuracy, polysomnography (PSG) has several drawbacks for diagnosing obstructive sleep apnea (OSA). Consequently, multiple portable monitors (PMs) have been proposed.
Objective
This systematic review aims to investigate the current literature to analyze the sets of physiological parameters captured by a PM to select the minimum number of such physiological signals while maintaining accurate results in OSA detection.
Methods
Inclusion and exclusion criteria for the selection of publications were established prior to the search. The evaluation of the publications was made based on one central question and several specific questions.
Results
The abilities to detect hypopneas, sleep time, or awakenings were some of the features studied to investigate the full functionality of the PMs to select the most relevant set of physiological signals. Based on the physiological parameters collected (one to six), the PMs were classified into sets according to the level of evidence. The advantages and the disadvantages of each possible set of signals were explained by answering the research questions proposed in the methods.
Conclusions
The minimum number of physiological signals detected by PMs for the detection of OSA depends mainly on the purpose and context of the sleep study. The set of three physiological signals showed the best results in the detection of OSA.
5-hydroxymethyl-furfural (HMF) and furfural are interesting as potential platform chemicals for a bio-based chemical production economy. Within the scope of this work, the process routes under technical development for the production of these platform chemicals were investigated. For two selected processes, the material and energy flows, as well as the carbon footprint, were examined in detail. The possible production process optimizations, further development potentials, and the research demand against the background of the reduction of the primary energy expenditure were worked out.
Improvement of a three-layered in vitro skin model for topical application of irritating substances
(2020)
In the field of skin tissue engineering, the development of physiologically relevant in vitro skin models comprising all skin layers, namely epidermis, dermis, and subcutis, is a great challenge. Increasing regulatory requirements and the ban on animal experiments for substance testing demand the development of reliable and in vivo-like test systems, which enable high-throughput screening of substances. However, the reproducibility and applicability of in vitro testing has so far been insufficient due to fibroblast-mediated contraction. To overcome this pitfall, an advanced 3-layered skin model was developed. While the epidermis of standard skin models showed an 80% contraction, the initial epidermal area of our advanced skin models was maintained. The improved barrier function of the advanced models was quantified by an indirect barrier function test and a permeability assay. Histochemical and immunofluorescence staining of the advanced model showed well-defined epidermal layers, a dermal part with distributed human dermal fibroblasts and a subcutis with round-shaped adipocytes. The successful response of these advanced 3-layered models for skin irritation testing demonstrated the suitability as an in vitro model for these clinical tests: only the advanced model classified irritative and non-irritative substances correctly. These results indicate that the advanced set up of the 3-layered in vitro skin model maintains skin barrier function and therefore makes them more suitable for irritation testing.
Stress is recognized as a factor of predominant disease and in the future the costs for treatment will increase. The presented approach tries to detect stress in a very basic and easy to implement way, so that the cost for the device and effort to wear it remain low. The user should benefit from the fact that the system offers an easy interface reporting the status of his body in real time. In parallel, the system provides interfaces to pass the obtained data forward for further processing and (professional) analyses, in case the user agrees. The system is designed to be used in every day’s activities and it is not restricted to laboratory use or environments. The implementation of the enhanced prototype shows that the detection of stress and the reporting can be managed using correlation plots and automatic pattern recognition even on a very light weighted microcontroller platform.
To evaluate the quality of sleep, it is important to determine how much time was spent in each sleep stage during the night. The gold standard in this domain is an overnight polysomnography (PSG). But the recording of the necessary electrophysiological signals is extensive and complex and the environment of the sleep laboratory, which is unfamiliar to the patient, might lead to distorted results. In this paper, a sleep stage detection algorithm is proposed that uses only the heart rate signal, derived from electrocardiogram (ECG), as a discriminator. This would make it possible for sleep analysis to be performed at home, saving a lot of effort and money. From the heart rate, using the fast Fourier transformation (FFT), three parameters were calculated in order to distinguish between the different sleep stages. ECG data along with a hypnogram scored by professionals was used from Physionet database, making it easy to compare the results. With an agreement rate of 41.3%, this approach is a good foundation for future research.
Increasing number of studies are focused on how adherent cells respond, in vitro, to different properties of a material. Typical properties are the surface chemistry, topographical cues (at the nano- and micro-scale) of the surface, and the substrate stiffness. Cell Response studies are of importance for designing new biomaterials with applications in cell culture technologies, regenerative medicine, or for medical implants. However, only very few studies take the cell age factor, respectively the donor age, into account. In this work, we tested two types of human vascular cells (smooth muscle and endothelial cells) from old and young donors on (a) micro-structured surfaces made of pol (dimethylsiloxane) or on (b) flat polyacrylamide hydrogels with varying stiffnesses. These experiments reveal age-dependent and cell typedependent differences in the cell response to the topography and stiffness, and may establish the Basis for further studies focusing on cell age-dependent responses.
Age-dependent migratory behavior of human endothelial cells revealed by substrate microtopography
(2019)
Cell migration is part of many important in vivo biological processes and is influenced by chemical and physical factors such as substrate topography. Although the migratory behavior of different cell types on structured substrates has already been investigated, up to date it is largely unknown if specimen's age affects cell migration on structures. In this work, we investigated age-dependent migratory behavior of human endothelial cells from young (≤ 31 years old) and old (≥ 60 years old) donors on poly(dimethylsiloxane) microstructured substrates consisting of well-defined parallel grooves. We observed a decrease in cell migration velocity in all substrate conditions and in persistence length perpendicular to the grooves in cells from old donors. Nevertheless, in comparison to young cells, old cells exhibited a higher cell directionality along grooves of certain depths and a higher persistence time. We also found a systematic decrease of donor age dependent responses of cell protrusions in orientation, velocity and length, all of them decreased in old cells. These observations lead us to hypothesize a possible impairment of actin cytoskeleton network and affected actin polymerization and steering systems, caused by aging.
Model-based hearing diagnosis based on wideband tympanometry measurements utilizing fuzzy arithmetic
(2019)
Today's audiometric methods for the diagnosis of middle ear disease are often based on a comparison of measurements with standard curves that represent the statistical range of normal hearing responses. Because of large inter-individual variances in the middle ear, especially in wideband tympanometry (WBT), specificity and quantitative evaluation are greatly restricted. A new model-based approach could transform today's predominantly qualitative hearing diganostics into a quantitative and tailored, patient-specific diagnosis, by evaluating WBT measurements with the aid of a middle-ear model. For this particular investigation, a finite element model of a human ear was used. It consisted of an acoustic ear canal and a tympanic cavity model, a middle-ear with detailed nonlinear models of the tympanic membrane and annular ligament, and a simplified inner-ear model. This model has made it possible to identify pathologies from measurements, by analyzing the parameters through senstivity studies and parameter clustering. Uncertainties due to the lack of knowledge, subjectivity in numerical implementation and model simplification are taken into account by the application of fuzzy arithmetic. The most confident parameter set can be determined by applying an inverse fuzzy method on the measurement data. The principle and the benefits of this model-based approach are illustrated by the example of a two-mass oscillator, and also by the simulation of the energy absorbance of an ear with malleus fixation, where the parameter changes that are introduced can be determined quantitatively through the system identification.
Drug-induced liver toxicity is one of the most common reasons for the failure of drugs in clinical trials and frequent withdrawal from the market. Reasons for such failures include the low predictive power of in vivo studies, that is mainly caused by metabolic differences between humans and animals, and intraspecific variances. In addition to factors such as age and genetic background, changes in drug metabolism can also be caused by disease-related changes in the liver. Such metabolic changes have also been observed in clinical settings, for example, in association with a change in liver stiffness, a major characteristic of an altered fibrotic liver. For mimicking these changes in an in vitro model, this study aimed to develop scaffolds that represent the rigidity of healthy and fibrotic liver tissue. We observed that liver cells plated on scaffolds representing the stiffness of healthy livers showed a higher metabolic activity compared to cells plated on stiffer scaffolds. Additionally, we detected a positive effect of a scaffold pre-coated with fetal calf serum (FCS)-containing media. This pre-incubation resulted in increased cell adherence during cell seeding onto the scaffolds. In summary, we developed a scaffold-based 3D model that mimics liver stiffness-dependent changes in drug metabolism that may more easily predict drug interaction in diseased livers.
Polyelectrolyte multilayer coatings (PEM) are prepared by alternative layer-by-layer deposition of cationic and anionic polyelectrolyte monolayers on charged surfaces. The thickness of the coatings ranges from nm to few μm. Their properties such as roughness, stiffness, surface charge and surface energy can be precisely tuned to fulfil different technical or biological requirements. The coating process is based on self-assembly of polyelectrolytes. Advantages of these coatings are their easy handling, no harsh chemistry and the possibility for coatings on complex geometries. The PEM coatings can be prepared from a variety of suitable polyelectrolytes. Their stability varies from very durable PEM coatings that are only soluble in strong solvents to quickly degradable, which may be applied as drug release system. One example of such a degradable PEM system is the one based on the polyelectrolyte pair Hyaluronan (HA) and Chitosan (CHI). These biopolymers originate from natural sources and show low toxicity towards human cells. However, HA/CHI multilayers show only weak adhesiveness for human umbilical vein endothelial cells (HUVEC). In this article, we summarize our approaches to enhance the HA/CHI multilayer by incorporation of a non-polymer substance –graphene oxide– to improve the cell adhesion and keep such properties as low cytotoxicity and biodegradability. Different approaches for incorporation of graphene oxide were performed and the cellular adhesion was tested by metabolic assay.
This article contains data on the synthesis and mechanical characterization of polysiloxane-based urea-elastomers (PSUs) and is related to the research article entitled “Influence of PDMS molecular weight on transparency and mechanical properties of soft polysiloxane-urea-elastomers for intraocular lens application” (Riehle et al., 2018) [1]. These elastomers were prepared by a two-step polyaddition using the aliphatic diisocyanate 4,4′-Methylenbis(cyclohexylisocyanate) (H12MDI), a siloxane-based chain extender 1,3-Bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane (APTMDS) and amino-terminated polydimethylsiloxanes (PDMS) or polydimethyl-methyl-phenyl-siloxane-copolymers (PDMS-Me,Ph), respectively. (More details about the synthesis procedure and the reaction scheme can be found in the related research article (Riehle et al., 2018) [1]).
Amino-terminated polydimethylsiloxanes with varying molecular weights and PDMS-Me,Ph-copolymers were prepared prior by a base-catalyzed ring-chain equilibration of a cyclic siloxane and the endblocker APTMDS. This DiB article contains a procedure for the synthesis of the base catalyst tetramethylammonium-3-aminopropyl-dimethylsilanolate and a generic synthesis procedure for the preparation of a PDMS having a targeted number average molecular weight of 3000 g mol−1. Molecular weights and the amount of methyl-phenyl-siloxane within the polysiloxane-copolymers were determined by 1H NMR and 29Si NMR spectroscopy. The corresponding NMR spectra and data are described in this article.
Additionally, this DiB article contains processed data on in line and off line FTIR-ATR spectroscopy, which was used to follow the reaction progress of the polyaddition by showing the conversion of the diisocyanate. All relevant IR band assignments of a polydimethylsiloxane-urea spectrum are described in this article.
Finally, data on the tensile properties and the mechanical hysteresis-behaviour at 100% elongation of PDMS-based polyurea-elastomers are shown in dependence to the PDMS molecular weight.
Cytocompatibility analyses of new implant materials or biomaterials are not only prescribed by the Medical Device Regulation (MDR), as defined in the DIN ISO Norm 10993-5 and -12, but are also increasingly replacing animal testing. In this context, jellyfish collagen has already been established as an alternative to mammalian collagen in different cell culture conditions, but a lack of knowledge exists about its applicability for cytocompatibility analyses of biomaterials. Thus, the present study was conducted to compare well plates coated with collagen type 0 derived from Rhizostoma pulmo with plates coated with bovine and porcine collagen. The coated well plates were analysed in vitro for their cytocompatibility, according to EN ISO 10993-5/−12, using both L929 fibroblasts and MC3T3 pre-osteoblasts. Thereby, the coated well plates were compared, using established materials as positive controls and a cytotoxic material, RM-A, as a negative control. L929 cells exhibited a significantly higher viability (#### p < 0.0001), proliferation (## p < 0.01), and a lower cytotoxicity (## p < 0.01 and # p < 0.05)) in the Jellagen® group compared to the bovine and porcine collagen groups. MC3T3 cells showed similar viability and acceptable proliferation and cytotoxicity in all collagen groups. The results of the present study revealed that the coating of well plates with collagen Type 0 derived from R. pulmo leads to comparable results to the case of well plates coated with mammalian collagens. Therefore, it is fully suitable for the in vitro analyses of the cytocompatibility of biomaterials or medical devices.
In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC) and DMPC1cholesterol (DMPC1 CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples.
Focal adhesion clusters (FAC) are dynamic and complex structures that help cells to sense physicochemical properties of their environment. Research in biomaterials, cell adhesion or cell migration often involves the visualization of FAC by fluorescence staining and microscopy, which necessitates quantitative analysis of FAC and other cell features in microscopy images using image processing. Fluorescence microscopy images of human umbilical vein endothelial cells (HUVEC) obtained at 63x magnification were quantitatively analysed using ImageJ software. A generalised algorithm for selective segmentation and morphological analysis of FAC, nucleus and cell morphology is implemented. Further, a method for discrimination of FACnear the nucleus and around the periphery is implemented using masks. Our algorithm is able to effectively quantify different morphological characteristics of cell components and shows a high sensitivity and specificity while providing a modular software implementation.
The spreading area of cells has been shown to play a central role in the determination of cell fate and tissue morphogenesis; however, a clear understanding of how spread cell area is determined is still lacking. The observation that cell area and force generally increase with substrate rigidity suggests that cell area is dictated mechanically, by means of a force-balance between the cell and the substrate. A simple mechanical model, corroborated by experimental measurements of cell area and force is presented to analyze the temporal force balance between the cell and the substrate during spreading. The cell is modeled as a thin elastic disc that is actively pulled by lamellipodia protrusions at the cell front. The essential molecular mechanisms of the motor activity at the cell front, including, actin polymerization, adhesion kinetics, and the actin retrograde flow, are accounted for and used to predict the dynamics of cell spreading on elastic substrates; simple, closed-form expressions for the evolution of cell size and force are derived. Time-resolved, traction force microscopy, combined with measurements of cell area are performed to investigate the simultaneous variations of cell size and force. We find that cell area and force increase simultaneously during spreading but the force develops with an apparent delay relative to the increase in cell area. We demonstrate that this may reflect the strain-stiffening property of the cytoskeleton. We further demonstrate that the radial cell force is a concave function of spreading speed and that this may reflect the strengthening of cell–substrate adhesions during spreading.
To improve the energy conversion efficiency of solar organic cells, the clue may lie in the development of devices inspired by an efficient light harvesting mechanism of some aquatic photosynthetic microorganisms that are adapted to low light intensity. Consequently, we investigated the pathways of excitation energy transfer (EET) from successive light harvesting pigments to the low energy level inside the phycobiliprotein antenna system of Acaryochloris marina, a cyanobacterium, using a time resolved absorption difference spectroscopy with a resolution time of 200 fs. The objective was to understand the actual biochemical process and pathways that determine the EET mechanism. Anisotropy of the EET pathway was calculated from the absorption change trace in order to determine the contribution of excitonic coupling. The results reveal a new electron energy relaxation pathway of 14 ps inside the phycocyanin component, which runs from phycocyanin to the terminal emitter. The bleaching of the 660 nm band suggests a broader absorption of the terminal emitter between 660 nm and 675 nm. Further, there are trimer depolarization kinetics of 450 fs and 500 fs in high and low ionic strength, respectively, which arise from the relaxation of the β84 and α84 in adjacent monomers of phycocyanin. Under conditions of low ionic strength buffer solution, the evolution of the kinetic amplitude during the depolarization of the trimer is suggestive of trimer conservation within the phycocyanin hexamer. The anisotropy values were 0.38 and 0.40 in high and in low ionic strength, respectively, indicating that there is no excitonic delocalization in the high energy level of phycocyanin hexamers.
Tissue constructs of physiologically relevant scale require a vascular system to maintain cell viability. However, in vitro vascularization of engineered tissues is still a major challenge. Successful approaches are based on a feeder layer (FL) to support vascularization. Here, we investigated whether the supporting effect on the self‐assembled formation of prevascular‐like structures by microvascular endothelial cells (mvECs) originates from the FL itself or from its extracellular matrix (ECM). Therefore, we compared the influence of ECM, either derived from adipose‐derived stem cells (ASCs) or adipogenically differentiated ASCs, with the classical cell‐based FL. All cell‐derived ECM (cdECM) substrates enabled mvEC growth with high viability. Prevascular‐like structures were visualized by immunofluorescence staining of endothelial surface protein CD31 and could be observed on all cdECM and FL substrates but not on control substrate collagen I. On adipogenically differentiated ECM, longer and higher branched structures could be found compared with stem cell cdECM. An increased concentration of proangiogenic factors was found in cdECM substrates and FL approaches compared with controls. Finally, the expression of proteins associated with tube formation (E‐selectin and thrombomodulin) was confirmed. These results highlight cdECM as promising biomaterial for adipose tissue engineering by inducing the spontaneous formation of prevascular‐like structures by mvECs.
Due to its availability and minimal invasive harvesting human adipose tissue-derived extracellular matrix (dECM) is often used as a biomaterial in various tissue engineering and healthcare applications. Next to dECM, cell-derived ECM (cdECM) can be generated by and isolated from in vitro cultured cells. So far both types of ECM were investigated extensively toward their application as (bio)material in tissue engineering and healthcare. However, a systematic characterization and comparison of soft tissue dECM and cdECM is still missing. In this study, we characterized dECM from human adipose tissue, as well as cdECM from human adipose-derived stem cells, toward their molecular composition, structural characteristics, and biological purity. The dECM was found to exhibit higher levels of collagens and lower levels of sulfated glycosaminoglycans compared with cdECMs. Structural characteristics revealed an immature state of the fibrous part of cdECM samples. By the identified differences, we aim to support researchers in the selection of a suitable ECM-based biomaterial for their specific application and the interpretation of obtained results.
How mechanical and physicochemical material characteristics influence adipose-derived stem cell fate
(2023)
Adipose-derived stem cells (ASCs) are a subpopulation of mesenchymal stem cells. Compared to bone marrow-derived stem cells, they can be harvested with minimal invasiveness. ASCs can be easily expanded and were shown to be able to differentiate into several clinically relevant cell types. Therefore, this cell type represents a promising component in various tissue engineering and medical approaches (e.g., cell therapy). In vivo cells are surrounded by the extracellular matrix (ECM) that provides a wide range of tissue-specific physical and chemical cues, such as stiffness, topography, and chemical composition. Cells can sense the characteristics of their ECM and respond to them in a specific cellular behavior (e.g., proliferation or differentiation). Thus, in vitro biomaterial properties represent an important tool to control ASCs behavior. In this review, we give an overview of the current research in the mechanosensing of ASCs and current studies investigating the impact of material stiffens, topography, and chemical modification on ASC behavior. Additionally, we outline the use of natural ECM as a biomaterial and its interaction with ASCs regarding cellular behavior.
Natural extracellular matrix (ECM) represents an ideal biomaterial for tissue engineering and regenerative medicine approaches. For further functionalization, there is a need for specific addressable functional groups within this biomaterial. Metabolic glycoengineering (MGE) provides a technique to incorporate modified monosaccharide derivatives into the ECM during their assembly, which was shown by us earlier for the production of a modified fibroblast-derived dermal ECM.
The extracellular matrix (ECM) is the non-cellular part of tissues and represents the natural environment of the cells. Next to structural stability, it provides various physical, chemical, and mechanical cues that strongly regulate and influence cellular behavior and are required for tissue morphogenesis, differentiation, and homeostasis. Due to its promising characteristics, ECM is used in a wide range of tissue engineering and regenerative medicine approaches as a biomaterial for coatings and scaffolds. To date, there are two sources for ECM material. First, native ECM is generated by the removal of the residing cells of a tissue or organ (decellularized ECM; dECM). Secondly, cell-derived ECM (cdECM) can be generated by and isolated from in vitro cultured cells. Although both types of ECM were intensively used for tissue engineering and regenerative medicine approaches, studies directly characterizing and comparing them are rare. Hence, in the first part of this thesis, dECM from adipose tissue and cdECM from stem cells and adipogenic differentiated stem cells from adipose tissue (ASCs) were characterized towards their macromolecular composition, structural features, and biological purity. The dECM was found to exhibit higher levels of collagens and lower levels of sulfated glycosaminoglycans compared to cdECMs. Structural characteristics revealed an immature state of collagen fibers in cdECM samples. The obtained results revealed differences between the two ECMs that can relevantly impact cellular behavior and subsequently experimental outcome and should therefore be considered when choosing a biomaterial for a specific application. The establishment of a functional vascular system in tissue constructs to realize an adequate nutrient supply remains challenging. In the second part, the supporting effect of cdECM on the self‐assembled formation of prevascular‐like structures by microvascular endothelial cells (mvECs) was investigated. It could be observed that cdECM, especially adipogenic differentiated cdECM, enhanced the formation of prevascular-like structures. An increased concentration of proangiogenic factors was found in cdECM substrates. The demonstration of cdECMs capability to induce the spontaneous formation of prevascular‐like structures by mvECs highlights cdECM as a promising biomaterial for adipose tissue engineering. Depending on the purpose of the ECM material chemical modification might be necessary. In the third and last part, the chemical functionalization of cdECM with dienophiles (terminal alkenes, cyclopropene) by metabolic glycoengineering (MGE) was demonstrated. MGE allows the chemical functionalization of cdECM via the natural metabolism of the cells and without affecting the chemical integrity of the cdECM. The incorporated dienophile chemical groups can be specifically addressed via catalysts-free, cell-friendly inverse electron-demand Diels‐Alder reaction. Using this system, the successful modification of cdECM from ASCs with an active enzyme could be shown. The possibility to modify cdECM via a cell-friendly chemical reaction opens up a wide range of possibilities to improve cdECM depending on the purpose of the material. Altogether, this thesis highlighted the differences between adipose dECM and cdECM from ASCs and demonstrated cdECM as a promising alternative to native dECM for application in tissue engineering and regenerative medicine approaches.
Endogenous electrical fields play an important role in various physiological and pathological events. Yet the effects of electrical cues on processes such as wound healing, tumor development or metastasis are still rarely investigated, though it is known that direct current electrical fields can alter cell migration or proliferation in vitro. Several 2D experimental models for studying cell responses to direct current electrical fields have been presented and characterized but suitable experimental models for electrotaxis studies in 3D are rare. Here we present a novel, easy-to-produce, multi-well-based galvanotactic-chamber for the use in 2D and 3D cell experiments for investigations on the influence of electrical fields on tumor cell migration and tumor spheroid growth. Our presented system allows the simultaneous application of electrical field to cells in four chambers, either cultured on the bottom of the culture-plate (2D) or embedded in hydrogel filled channels(3D). The set-up is also suitable for, live-cell-imaging. Validation tests show stable electrical fields and high cell viabilities inside the channel. Tumor spheroids of various diameters can be exposed to direct current electrical fields up to one week.
Soft lithography, a tool widely applied in biology and life sciences with numerous applications, uses the soft molding of photolithography-generated master structures by polymers. The central part of a photolithography set-up is a mask-aligner mostly based on a high-pressure mercury lamp as an ultraviolet (UV) light source. This type of light source requires a high level of maintenance and shows a decreasing intensity over its lifetime, influencing the lithography outcome. In this paper, we present a low-cost, bench-top photolithography tool based on ninety-eight 375 nm light-emitting diodes (LEDs). With approx. 10 W, our presented lithography set-up requires only a fraction of the energy of a conventional lamp, the LEDs have a guaranteed lifetime of 1000 h, which becomes noticeable by at least 2.5 to 15 times more exposure cycles compared to a standard light source and with costs less than 850 C it is very affordable. Such a set-up is not only attractive to small academic and industrial fabrication facilities who want to enable work with the technology of photolithography and cannot afford a conventional set-up, but also microfluidic teaching laboratories and microfluidic research and development laboratories, in general, could benefit from this cost-effective alternative. With our self-built photolithography system, we were able to produce structures from 6 μm to 50 μm in height and 10 μm to 200 μm in width. As an optional feature, we present a scaled-down laminar flow hood to enable a dust-free working environment for the photolithography process.
Ultra wideband real-time locating system for tracking people and devices in the operating room
(2022)
Position tracking within the OR could be one possible input for intraoperative situation recognition. Our approach demonstrates a Real-time Locating System (RTLS) using the Ultra Wideband (UWB) technology to determine the position of people or objects. The UWB RTLS was integrated into the research OR at Reutlingen University and the system’s settings were optimized regarding the four factors accuracy, susceptibility to interference, range, and latency. Therefore, different parameters were adapted and the effects on the factors were compared. Goodtracking quality could be achieved under optimal settings. These results indicate that a UWB RTLS is well suited to determine the position of people and devices in our setting. The feasibility of the system needsto be evaluated under real OR conditions.
At the beginning of 2022, Frontiers in Bioengineering and Biotechnology - Biomaterials Section has published a Research Topic on “Functional Surfaces and Biomaterials.” The aim of this Research Topic is to summarize the current state of research and development in the field of functional surfaces and biomaterials with a particular focus on biotechnological and medical applications.
The guest editorial team would like to thank all colleagues from around the world who submitted their reviews and research articles for the Research Topic. By the end of August 2022, we have successfully collected 20 articles by 138 participating authors following the peer review process. We also tried to select manuscripts from different research areas to cover the most relevant Research Topic of interest, from drug delivery systems to bone tissue engineering to biosensors and general aspects in biomedicine. By the end of December, the 20 articles had been viewed for more than 21000 times with downloads more than 4,000 times, and 11 articles have reached more than 1,000 views.