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- ItemLike a Second Skin: Understanding How Epidermal Devices Affect Human Tactile Perception(New York,NY,United States : Association for Computing Machinery, 2019) Nittala, Aditya Shekhar; Kruttwig, Klaus; Lee, Jaeyeon; Bennewitz, Roland; Arzt, Eduard; Steimle, Jürgen; Brewster, StephenThe emerging class of epidermal devices opens up new opportunities for skin-based sensing, computing, and interaction. Future design of these devices requires an understanding of how skin-worn devices affect the natural tactile perception. In this study, we approach this research challenge by proposing a novel classification system for epidermal devices based on flexural rigidity and by testing advanced adhesive materials, including tattoo paper and thin films of poly (dimethylsiloxane) (PDMS). We report on the results of three psychophysical experiments that investigated the effect of epidermal devices of different rigidity on passive and active tactile perception. We analyzed human tactile sensitivity thresholds, two-point discrimination thresholds, and roughness discrimination abilities on three different body locations (fingertip, hand, forearm). Generally, a correlation was found between device rigidity and tactile sensitivity thresholds as well as roughness discrimination ability. Surprisingly, thin epidermal devices based on PDMS with a hundred times the rigidity of commonly used tattoo paper resulted in comparable levels of tactile acuity. The material offers the benefit of increased robustness against wear and the option to re-use the device. Based on our findings, we derive design recommendations for epidermal devices that combine tactile perception with device robustness.
- ItemSemantic segmentation of non-linear multimodal images for disease grading of inflammatory bowel disease: A segnet-based application([Sétubal] : SCITEPRESS - Science and Technology Publications Lda., 2019) Pradhan, Pranita; Meyer, Tobias; Vieth, Michael; Stallmach, Andreas; Waldner, Maximilian; Schmitt, Michael; Popp, Juergen; Bocklitz, Thomas; De Marsico, Maria; Sanniti di Baja, Gabriella; Fred, AnaNon-linear multimodal imaging, the combination of coherent anti-stokes Raman scattering (CARS), two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), has shown its potential to assist the diagnosis of different inflammatory bowel diseases (IBDs). This label-free imaging technique can support the ‘gold-standard’ techniques such as colonoscopy and histopathology to ensure an IBD diagnosis in clinical environment. Moreover, non-linear multimodal imaging can measure biomolecular changes in different tissue regions such as crypt and mucosa region, which serve as a predictive marker for IBD severity. To achieve a real-time assessment of IBD severity, an automatic segmentation of the crypt and mucosa regions is needed. In this paper, we semantically segment the crypt and mucosa region using a deep neural network. We utilized the SegNet architecture (Badrinarayanan et al., 2015) and compared its results with a classical machine learning approach. Our trained SegNet mod el achieved an overall F1 score of 0.75. This model outperformed the classical machine learning approach for the segmentation of the crypt and mucosa region in our study.
- ItemQuantification of osseointegration of plasma-polymer coated titanium alloyed implants by means of microcomputed tomography versus histomorphometry(New York [u.a.] : Hindawi, 2015) Gabler, Carolin; Zietz, Carmen; Bieck, Richard; Göhler, Rebecca; Lindner, Tobias; Haenle, Maximilian; Finke, Birgit; Meichsner, Jürgen; Testrich, Holger; Nowottnick, Mathias; Frerich, Bernhard; Bader, RainerA common method to derive both qualitative and quantitative data to evaluate osseointegration of implants is histomorphometry. The present study describes a new image reconstruction algorithm comparing the results of bone-to-implant contact (BIC) evaluated by means of µCT with histomorphometry data. Custom-made conical titanium alloyed (Ti6Al4V) implants were inserted in the distal tibial bone of female Sprague-Dawley rats. Different surface configurations were examined: Ti6Al4V implants with plasma-polymerized allylamine (PPAAm) coating and plasma-polymerized ethylenediamine (PPEDA) coating as well as implants without surface coating. After six weeks postoperatively, tibiae were explanted and BIC was determined by µCT (3D) and afterwards by histomorphometry (2D). In comparison to uncoated Ti6Al4V implants demonstrating low BIC of 32.4% (histomorphometry) and 51.3% (µCT), PPAAm and PPEDA coated implants showed a nonsignificant increase in BIC (histomorphometry: 45.7% and 53.5% and µCT: 51.8% and 62.0%, resp.). Mean BIC calculated by µCT was higher for all surface configurations compared to BIC detected by histomorphometry. Overall, a high correlation coefficient of 0.70 () was found between 3D and 2D quantification of BIC. The μCT analysis seems to be suitable as a nondestructive and accurate 3D imaging method for the evaluation of the bone-implant interface.
- ItemBioinspired Liposomes for Oral Delivery of Colistin to Combat Intracellular Infections by Salmonella enterica(Weinheim : Wiley-VCH, 2019) Menina, S.; Eisenbeis, J.; Kamal, M.A.M.; Koch, M.; Bischoff, M.; Gordon, S.; Loretz, B.; Lehr, C.-M.Bacterial invasion into eukaryotic cells and the establishment of intracellular infection has proven to be an effective means of resisting antibiotic action, as anti-infective agents commonly exhibit a poor permeability across the host cell membrane. Encapsulation of anti-infectives into nanoscaled delivery systems, such as liposomes, is shown to result in an enhancement of intracellular delivery. The aim of the current work is, therefore, to formulate colistin, a poorly permeable anti-infective, into liposomes suitable for oral delivery, and to functionalize these carriers with a bacteria-derived invasive moiety to enhance their intracellular delivery. Different combinations of phospholipids and cholesterol are explored to optimize liposomal drug encapsulation and stability in biorelevant media. These liposomes are then surface-functionalized with extracellular adherence protein (Eap), derived from Staphylococcus aureus. Treatment of HEp-2 and Caco-2 cells infected with Salmonella enterica using colistin-containing, Eap-functionalized liposomes resulted in a significant reduction of intracellular bacteria, in comparison to treatment with nonfunctionalized liposomes as well as colistin alone. This indicates that such bio-invasive carriers are able to facilitate intracellular delivery of colistin, as necessary for intracellular anti-infective activity. The developed Eap-functionalized liposomes, therefore, present a promising strategy for improving the therapy of intracellular infections. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
- ItemThe Biomedical Use of Silk: Past, Present, Future(Weinheim : Wiley-VCH, 2019) Holland, Chris; Numata, Keiji; Rnjak-Kovacina, Jelena; Seib, F. PhilippHumans have long appreciated silk for its lustrous appeal and remarkable physical properties, yet as the mysteries of silk are unraveled, it becomes clear that this outstanding biopolymer is more than a high-tech fiber. This progress report provides a critical but detailed insight into the biomedical use of silk. This journey begins with a historical perspective of silk and its uses, including the long-standing desire to reverse engineer silk. Selected silk structure–function relationships are then examined to appreciate past and current silk challenges. From this, biocompatibility and biodegradation are reviewed with a specific focus of silk performance in humans. The current clinical uses of silk (e.g., sutures, surgical meshes, and fabrics) are discussed, as well as clinical trials (e.g., wound healing, tissue engineering) and emerging biomedical applications of silk across selected formats, such as silk solution, films, scaffolds, electrospun materials, hydrogels, and particles. The journey finishes with a look at the roadmap of next-generation recombinant silks, especially the development pipeline of this new industry for clinical use. © 2018 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
- ItemNonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting(Weinheim : Wiley-VCH, 2019) Haryadi, Bernard Manuel; Hafner, Daniel; Amin, Ihsan; Schubel, Rene; Jordan, Rainer; Winter, Gerhard; Engert, JuliaThe shape of nanoparticles is known recently as an important design parameter influencing considerably the fate of nanoparticles with and in biological systems. Several manufacturing techniques to generate nonspherical nanoparticles as well as studies on in vitro and in vivo effects thereof have been described. However, nonspherical nanoparticle shape stability in physiological-related conditions and the impact of formulation parameters on nonspherical nanoparticle resistance still need to be investigated. To address these issues, different nanoparticle fabrication methods using biodegradable polymers are explored to produce nonspherical nanoparticles via the prevailing film-stretching method. In addition, systematic comparisons to other nanoparticle systems prepared by different manufacturing techniques and less biodegradable materials (but still commonly utilized for drug delivery and targeting) are conducted. The study evinces that the strong interplay from multiple nanoparticle properties (i.e., internal structure, Young's modulus, surface roughness, liquefaction temperature [glass transition (Tg) or melting (Tm)], porosity, and surface hydrophobicity) is present. It is not possible to predict the nonsphericity longevity by merely one or two factor(s). The most influential features in preserving the nonsphericity of nanoparticles are existence of internal structure and low surface hydrophobicity (i.e., surface-free energy (SFE) > ≈55 mN m−1, material–water interfacial tension <6 mN m−1), especially if the nanoparticles are soft (<1 GPa), rough (Rrms > 10 nm), porous (>1 m2 g−1), and in possession of low bulk liquefaction temperature (<100 °C). Interestingly, low surface hydrophobicity of nanoparticles can be obtained indirectly by the significant presence of residual stabilizers. Therefore, it is strongly suggested that nonsphericity of particle systems is highly dependent on surface chemistry but cannot be appraised separately from other factors. These results and reviews allot valuable guidelines for the design and manufacturing of nonspherical nanoparticles having adequate shape stability, thereby appropriate with their usage purposes. Furthermore, they can assist in understanding and explaining the possible mechanisms of nonspherical nanoparticles effectivity loss and distinctive material behavior at the nanoscale. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
- ItemPolyphenols delivery by polymeric materials: challenges in cancer treatment(Abingdon : Taylor & Francis Group, 2017-2-3) Vittorio, Orazio; Curcio, Manuela; Cojoc, Monica; Goya, Gerardo F.; Hampel, Silke; Iemma, Francesca; Dubrovska, Anna; Cirillo, GiuseppeNanotechnology can offer different solutions for enhancing the therapeutic efficiency of polyphenols, a class of natural products widely explored for a potential applicability for the treatment of different diseases including cancer. While possessing interesting anticancer properties, polyphenols suffer from low stability and unfavorable pharmacokinetics, and thus suitable carriers are required when planning a therapeutic protocol. In the present review, an overview of the different strategies based on polymeric materials is presented, with the aim to highlight the strengths and the weaknesses of each approach and offer a platform of ideas for researchers working in the field.
- ItemRisk assessment of kINPen plasma treatment of four human pancreatic cancer cell lines with respect to metastasis(Basel : MDPI AG, 2019) Bekeschus, Sander; Freund, Eric; Spadola, Chiara; Privat-Maldonado, Angela; Hackbarth, Christine; Bogaerts, Annemie; Schmidt, Anke; Wende, Kristian; Weltmann, Klaus-Dieter; Woedtke, Thomas von; Heidecke, Claus-Dieter; Partecke, Lars-Ivo; Käding, AndréCold physical plasma has limited tumor growth in many preclinical models and is, therefore, suggested as a putative therapeutic option against cancer. Yet, studies investigating the cells’ metastatic behavior following plasma treatment are scarce, although being of prime importance to evaluate the safety of this technology. Therefore, we investigated four human pancreatic cancer cell lines for their metastatic behavior in vitro and in chicken embryos (in ovo). Pancreatic cancer was chosen as it is particularly metastatic to the peritoneum and systemically, which is most predictive for outcome. In vitro, treatment with the kINPen plasma jet reduced pancreatic cancer cell activity and viability, along with unchanged or decreased motility. Additionally, the expression of adhesion markers relevant for metastasis was down-regulated, except for increased CD49d. Analysis of 3D tumor spheroid outgrowth showed a lack of plasma-spurred metastatic behavior. Finally, analysis of tumor tissue grown on chicken embryos validated the absence of an increase of metabolically active cells physically or chemically detached with plasma treatment. We conclude that plasma treatment is a safe and promising therapeutic option and that it does not promote metastatic behavior in pancreatic cancer cells in vitro and in ovo. © 2019 by the authors.
- ItemCharacterization and prediction of the mechanism of action of antibiotics through NMR metabolomics(London : BioMed Central, 2016) Hoerr, Verena; Duggan, Gavin E.; Zbytnuik, Lori; Poon, Karen K.H.; Große, Christina; Neugebauer, Ute; Methling, Karen; Löffler, Bettina; Vogel, Hans J.Background: The emergence of antibiotic resistant pathogenic bacteria has reduced our ability to combat infectious diseases. At the same time the numbers of new antibiotics reaching the market have decreased. This situation has created an urgent need to discover novel antibiotic scaffolds. Recently, the application of pattern recognition techniques to identify molecular fingerprints in ‘omics’ studies, has emerged as an important tool in biomedical research and laboratory medicine to identify pathogens, to monitor therapeutic treatments or to develop drugs with improved metabolic stability, toxicological profile and efficacy. Here, we hypothesize that a combination of metabolic intracellular fingerprints and extracellular footprints would provide a more comprehensive picture about the mechanism of action of novel antibiotics in drug discovery programs. Results: In an attempt to integrate the metabolomics approach as a classification tool in the drug discovery processes, we have used quantitative 1H NMR spectroscopy to study the metabolic response of Escherichia coli cultures to different antibiotics. Within the frame of our study the effects of five different and well-known antibiotic classes on the bacterial metabolome were investigated both by intracellular fingerprint and extracellular footprint analysis. The metabolic fingerprints and footprints of bacterial cultures were affected in a distinct manner and provided complementary information regarding intracellular and extracellular targets such as protein synthesis, DNA and cell wall. While cell cultures affected by antibiotics that act on intracellular targets showed class-specific fingerprints, the metabolic footprints differed significantly only when antibiotics that target the cell wall were applied. In addition, using a training set of E. coli fingerprints extracted after treatment with different antibiotic classes, the mode of action of streptomycin, tetracycline and carbenicillin could be correctly predicted. Conclusion: The metabolic profiles of E. coli treated with antibiotics with intracellular and extracellular targets could be separated in fingerprint and footprint analysis, respectively and provided complementary information. Based on the specific fingerprints obtained for different classes of antibiotics, the mode of action of several antibiotics could be predicted. The same classification approach should be applicable to studies of other pathogenic bacteria.
- ItemNaturally drug-loaded chitin: Isolation and applications(Basel : MDPI, 2019) Kovalchuk, Valentine; Voronkina, Alona; Binnewerg, Björn; Schubert, Mario; Muzychka, Liubov; Wysokowski, Marcin; Tsurkan, Mikhail V.; Bechmann, Nicole; Petrenko, Iaroslav; Fursov, Andriy; Martinovic, Rajko; Ivanenko, Viatcheslav N.; Fromont, Jane; Smolii, Oleg B.; Joseph, Yvonne; Giovine, Marco; Erpenbeck, Dirk; Gelinsky, Michael; Springer, Armin; Guan, Kaomei; Bornstein, Stefan R.; Ehrlich, HermannNaturally occurring three-dimensional (3D) biopolymer-based matrices that can be used in different biomedical applications are sustainable alternatives to various artificial 3D materials. For this purpose, chitin-based structures from marine sponges are very promising substitutes. Marine sponges from the order Verongiida (class Demospongiae) are typical examples of demosponges with well-developed chitinous skeletons. In particular, species belonging to the family Ianthellidae possess chitinous, flat, fan-like fibrous skeletons with a unique, microporous 3D architecture that makes them particularly interesting for applications. In this work, we focus our attention on the demosponge Ianthella flabelliformis (Linnaeus, 1759) for simultaneous extraction of both naturally occurring (“ready-to-use”) chitin scaffolds, and biologically active bromotyrosines which are recognized as potential antibiotic, antitumor, and marine antifouling substances. We show that selected bromotyrosines are located within pigmental cells which, however, are localized within chitinous skeletal fibers of I. flabelliformis. A two-step reaction provides two products: treatment with methanol extracts the bromotyrosine compounds bastadin 25 and araplysillin-I N20 sulfamate, and a subsequent treatment with acetic acid and sodium hydroxide exposes the 3D chitinous scaffold. This scaffold is a mesh-like structure, which retains its capillary network, and its use as a potential drug delivery biomaterial was examined for the first time. The results demonstrate that sponge-derived chitin scaffolds, impregnated with decamethoxine, effectively inhibit growth of the human pathogen Staphylococcus aureus in an agar diffusion assay