Germany Introduction Research Articles

Alive and Kicking: Electoral Reform in Germany Introduction to the Special Issue

Alive and Kicking: Electoral Reform in Germany Introduction to the Special Issue

Bewertung und Folgen der SARS-CoV-2-Infektionsschutzmaßnahmen an Schulen. Ergebnisse von Fokusgruppen-Befragungen unter Lehrkräften in Deutschland

Evaluation and consequences of SARS-CoV-2 infection control measures in schools. Findings of focus group interviews among teachers in Germany Introduction: In order to stem the spread of the SARS-CoV-2 pandemic, there were wide-ranging changes in the school setting from March 2020 onwards, characterised by changing teaching formats (alternating between distance, face-to-face and hybrid teaching) and the implementation of infection control measures. Aim and Method: The aim of the present study was to investigate the evaluation of these measures and the consequences for teachers in Germany and to formulate best practice examples for school education in the further course of the pandemic. For this purpose, focus group interviews were conducted with 17 teachers at four schools and evaluated by content analysis. Results: It was found that the teachers felt burdened by teaching under pandemic conditions and that their health behaviour had deteriorated. In addition, new pandemic-related fears arose and the implementation of infection control measures (implementation of AHA-L rules (distance, hygiene, mask, ventilation), performance of SARS-CoV-2 tests) was accompanied by workrelated and health-related problems. The quality of training of prospective teachers was also questioned. The introduction of SARS-CoV-2 vaccinations and the relatively high ranking of teachers in prioritisation was experienced as a relief and very much welcomed. In places, difficulties in communicating and implementing infection control measures were reported, resulting in the formulation of best practices, such as the implementation of SARS-CoV-2 testing by trained staff or the formulation of school form-specific measures. Conclusions: The stress caused by teaching during the pandemic and the negative development of health behaviour represent a relevant public health risk. For this reason, the idea of prevention and health promotion should or must be intensified even more during the SARS-CoV-2 pandemic, further developed in view of the pandemic specifics and applied in the living environments. Keywords: Corona – COVID-19 – school – teachers

Einfluss von Fatigue und kognitiven Einschränkungen auf die Inanspruchnahme von Gesundheitsleistungen, Arbeitsleistung und Lebensqualität (Utility)

Influence of fatigue and cognitive impairment on the use of health services, work performance and quality of life (utility): A study with 5,475 patients with multiple sclerosis in Germany Introduction: People with multiple sclerosis (MS) experience a number of neurological problems beyond the general outcome measures of relapses and disability that can independently affect costs and quality of life. Objectives: To investigate the effect of self-assessed fatigue and subjective cognitive impairment on direct healthcare consumption, work participation and utility in Germany. Methods: The study included 5,475 participants and investigated – in addition to all resource consumption – fatigue, cognitive impairment and the effect of MS while at work using visual analogue scales (VAS 0–10). The analysis controlled for gender, age, disease duration, education, disability, and use of disease-modifying treatments. Results: The level of fatigue and cognitive impairment was significantly and independently correlated with all resource utilisation, workforce participation and utility (p<0.0001). For each VAS point increase in severity, the probability of working was reduced by 10.6% for cognitive impairment and 4.9% for fatigue, while utility decreased by 0.03 for each point. Work hours decreased in linear fashion with each point of increasing severity for both symptoms, while sick leave increased accordingly. Both symptoms significantly affected productivity at work. Conclusions: The effect of fatigue and impaired cognition on work capacity has been shown in an international study, but demonstrating their effect on resource consumption requires a large single-country sample. This German analysis demonstrates their effect on all economic resources, both direct and indirect.

Demonstrating brain-level interactions between working memory load and driving demand level using fNIRS

Demonstrating brain-level interactions between working memory load and driving demand level using fNIRS

The somatogravic illusion during centrifugation: sex differences

Maintaining orientation in an environment with non-Earth gravity (1 g) is critical for an astronaut's operational performance. Such environments present a number of complexities for balance and motion. For example, when an astronaut tilts due to ascending or descending an inclined plane on the moon, the gravity vector will be tilted correctly, but the magnitude will be different from on earth. If this results in a mis-perceived tilt, then that may lead to postural and perceptual errors, such as mis-perceiving the orientation of oneself or the ground plane and corresponding errors in task judgment.

Cerebrospinal fluid from Dementia with Lewy body patients suppresses neuronal network activity

Cerebrospinal fluid from Dementia with Lewy body patients suppresses neuronal network activity

Evidence for language-specificity of a BCI-based language training

Evidence for language-specificity of a BCI-based language training

Demonstrating brain-level interactions between working memory load and frustration while driving using functional near-infrared spectroscopy

Demonstrating brain-level interactions between working memory load and frustration while driving using functional near-infrared spectroscopy

Bringing transparent microelectrodes to market: Evaluation for production and real-world applications

Event Abstract Back to Event Bringing transparent microelectrodes to market: Evaluation for production and real-world applications Michael Mierzejewski1, Pranoti Kshirsagar1, Udo Kraushaar1, Gerhard Heusel1, Ramona Samba2 and Peter D. Jones1* 1 Natural and Medical Sciences Institute, Germany 2 NMI Technologie Transfer GmbH, Germany Introduction Microelectrode arrays (MEAs) are used for a number of applications in electrophysiology, with the ability to record field action potentials (fAP) from cardiomyocytes and neurons, as well as selectively induce a potential on an electrode in the array. This technology makes high throughput monitoring of field potentials possible, but the materials used in commercially-available MEAs can inhibit visual recording or stimulation. While transparent conductors such as indium tin oxide (ITO) are used for conducting traces, the need for microelectrodes to have stable, low electrochemical impedance has necessitated the use of opaque materials such as titanium nitride (TiN), gold (Au), platinum (Pt), and platinum iridium (Pt/Ir). Any bright-field microscopy will lead to a shadow being cast onto the cells above the electrode, resulting in a loss of potentially useful information. To remedy this issue, several groups have been working on transparent microelectrode materials such as Au-mesh coated with conducting polymer [1] and carbon nanomaterials [2-5]. To the best of our knowledge, no MEA with transparent microelectrodes is currently commercially available. The purpose of this project is to evaluate multiple transparent materials to complement those opaque materials currently on the market. Specifically, we are investigating the material properties, suitability for scalable production, stability against sterilization and during cell culture, and evaluating their application in opto- and electrophysiology in cardiac and neural applications. This technology has the potential to advance the current trend of combining electrophysiology with optophysiology. Materials and Methods We are evaluating various transparent materials against state-of-the-art titanium nitride (TiN) microelectrodes. Standard (opaque) and transparent titanium nitride microelectrodes have been fabricated in an 8x8 MEA configuration with ITO traces, SiNx as the insulator, electrode size of 30 µm, and pitch of 200 µm. Carbon nanomaterials and conducting polymers are also being considered as potential materials for transparent electrodes. Impedance spectroscopy was performed with a Bio-logic VMP3 potentiostat at an amplitude of 10 mV from 1 Hz to 100 kHz. Noise measurements were performed using 150 mM phosphate buffered saline (PBS) as the medium, utilizing a MEA2100-system from Multi Channel Systems (MCS). Cardiomyocytes were isolated from embryonic chicken ventricles after 13 days in incubation, and 80 k cells were subsequently plated on each MEA after coating with nitrocellulose. Recordings were taken of these samples in a 3 % Fetal Calf Serum (FCS) medium after 6 days in vitro. Optical transmission measurements were taken with a bright-field Zeiss microscope, performing a line scan across the electrodes. Results and Discussion Characterization of the transparent electrodes showed an increase in transparency, noise, and impedance in comparison to the standard electrodes. An increase in impedance of ~150 kΩ (Figure 1b) led to an increase in peak-to-peak noise of 10 µV when compared against standard opaque electrodes. This increase of impedance and noise is accompanied by a 40 % absolute increase in transmission of light in the visible spectrum (400–700 nm) as shown in Figure 1d. The electrodes were then compared against each other in a real world application. Measurement of fAP from the cardiomyocytes showed the effect of the increased noise and transmission observed during the characterization. This increase in noise affected the clarity of the cardiomyocyte recordings, but cellular activity such as the repolarization event in Figure 1c was still visible. While the recordings were impacted by the characteristics of the transparent material, the increased transmission allowed for cells on top of the electrode to be visible under bright-field spectroscopy. Conclusion and Outlook Preliminary results show that increased transparency can be attained in exchange for increased impedance, and subsequent increased noise. The increase in transparency does allow for the ability to view cells which would normally be obstructed by the electrode. This will provide new capabilities for specific applications where observation or optical stimulation of the cells is important to the application. With continued work on this project we aim to further evaluate transparent TiN as well as materials including carbon nanomaterials and conducting polymers. Along with testing the impedance and noise of all the electrodes, we plan to put the MEAs through real world scenarios to see how well they can be used in research applications. This will include investigating the limits that the MEAs can withstand regarding standard cleaning and sterilization procedures, as well as how well the MEAs withstand extended or repeated cell cultures. Figure 1 Figure 2 Acknowledgements We thank the NMI TT GmbH for supporting MEA fabrication, Sandra Buckenmaier for cardiomyocyte cell culturing and Simon Dickreuter for optical transmittance measurements.

Variability in clinical chemistry parameters in healthy male volunteers prior to drug administration, an overview of Bayer in-house phase I trials from 2000 - 2013 INSERT TABLE AST and γGT values are less affected. Conclusion: A 24h predose lab sample may

Event Abstract Back to Event Variability in clinical chemistry parameters in healthy male volunteers prior to drug administration, an overview of Bayer in-house phase I trials from 2000 - 2013 INSERT TABLE AST and γGT values are less affected. Conclusion: A 24h predose lab sample may Georg Wensing1 1 Bayer AG, Department of Clinical Pharmacology CV/HEM, Germany Introduction: Recently consensus results on pivotal eligibility criteria for healthy volunteers (HVs) for clinical trials were published. Baseline evaluations immediately prior to dosing were not recommended to confirm inclusion/exclusion criteria. Method: We reviewed all BAYER Phase I trials performed at the Institute of Clinical Pharmacology (Wuppertal) and ClinPharm Cologne between 2000 and 2013. Key parameters were: AST, ALT, GLDH, γGT, total bilirubin, CK, Amylase, lipase, creatinine. All parameters were compared at screening, at 24 hours and 0 hours before dosing. Results: In total, more than 35712 blood samples from 4300 healthy male subjects (aged 18-70 years) were investigated. A wide variability of laboratory parameters exceeding the upper limit of normal (ULN) at all time points was observed. Generally, the incidence of values above ULN is reduced from screening, to 24 and 0 hours before administration. However, despite of a reduced number of HVs from screening to 24 and 0 hours due to rigid inclusion/exclusion criteria there is still a substantial percentage of values above ULN 24h and 0h predose. INSERT TABLE - image 4 AST and γGT values are less affected. Conclusion: A 24h predose lab sample may help to confirm inclusion/exclusion criteria and reduce the number of HVs with abnormal lab values entering the trial. A 0 hour sample should be mandatory to interpret abnormal values under treatment. Acknowledgements no Keywords: variability, Phase I, Healthy male subjects, Clinical chemistry parameters, prior drug administration Conference: EUFEMED 2017, London, United Kingdom, 17 May - 19 May, 2017. Presentation Type: Poster Topic: EUFEMED 2017 CONFERENCE Citation: Wensing G (2019). Variability in clinical chemistry parameters in healthy male volunteers prior to drug administration, an overview of Bayer in-house phase I trials from 2000 - 2013 INSERT TABLE AST and γGT values are less affected. Conclusion: A 24h predose lab sample may. Front. Pharmacol. Conference Abstract: EUFEMED 2017. doi: 10.3389/conf.fphar.2017.62.00018 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Aug 2017; Published Online: 25 Jan 2019. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Georg Wensing Google Georg Wensing Google Scholar Georg Wensing PubMed Georg Wensing Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Variability in clinical chemistry parameters in healthy male volunteers prior to drug administration, an overview of Bayer in-house phase I trials from 2000 - 2013

Event Abstract Back to Event VARIABILITY OF CLINICAL CHEMISTRY PARAMETERS IN HEALTHY MALE VOLUNTEERS PRIOR TO DRUG ADMINISTRATION – AN OVERVIEW OF BAYER IN-HOUSE PHASE I TRIALS FROM 2000 – 2013 Michael F. Boettcher1* and Georg Wensing1 1 Bayer AG, Department of Clinical Pharmacology CV/HEM, Germany Introduction: Recently consensus results on pivotal eligibility criteria for healthy volunteers (HVs) for clinical trials were published. Baseline evaluations immediately prior to dosing were not recommended to confirm inclusion/exclusion criteria. Method: We reviewed all BAYER Phase I trials performed at the Institute of Clinical Pharmacology (Wuppertal) and ClinPharm Cologne between 2000 and 2013. Key parameters were: AST, ALT, GLDH, γGT, total bilirubin, CK, Amylase, lipase, creatinine. All parameters were compared at screening, at 24 hours and 0 hours before dosing. Results: In total, more than 35712 blood samples from 4300 healthy male subjects (aged 18-70 years) were investigated. A wide variability of laboratory parameters exceeding the upper limit of normal (ULN) at all time points was observed. Generally, the incidence of values above ULN is reduced from screening, to 24 and 0 hours before administration. However, despite of a reduced number of HVs from screening to 24 and 0 hours due to rigid inclusion/exclusion criteria there is still a substantial percentage of values above ULN 24h and 0h predose. AST and γGT values are less affected. Conclusion: A 24h predose lab sample may help to confirm inclusion/exclusion criteria and reduce the number of HVs with abnormal lab values entering the trial. A 0 hour sample should be mandatory to interpret abnormal values under treatment. Keywords: variability, Phase I, Healthy male subjects, Clinical chemistry parameters, prior drug administration Conference: EUFEMED 2017, London, United Kingdom, 17 May - 19 May, 2017. Presentation Type: Poster Topic: EUFEMED 2017 CONFERENCE Citation: Boettcher MF and Wensing G (2019). VARIABILITY OF CLINICAL CHEMISTRY PARAMETERS IN HEALTHY MALE VOLUNTEERS PRIOR TO DRUG ADMINISTRATION – AN OVERVIEW OF BAYER IN-HOUSE PHASE I TRIALS FROM 2000 – 2013. Front. Pharmacol. Conference Abstract: EUFEMED 2017. doi: 10.3389/conf.fphar.2017.62.00001 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Aug 2017; Published Online: 25 Jan 2019. * Correspondence: Dr. Michael F Boettcher, Bayer AG, Department of Clinical Pharmacology CV/HEM, Wuppertal, Germany, michael-friedrich.boettcher@bayer.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Michael F Boettcher Georg Wensing Google Michael F Boettcher Georg Wensing Google Scholar Michael F Boettcher Georg Wensing PubMed Michael F Boettcher Georg Wensing Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Functional characterization of EZH2 in pancreatic carcinogenesis

ID: 1413. Dual specificity kinase TTK in pancreatic neuroendocrine cancer Marina Hutzler , Harald Schmidt , Brajesh Kaistha , Rita Lawlor , Aldo Scarpa , Thomas Gress , Malte Buchholz 1 Gastroenterology and Endocrinology, Philipps University Marburg, Marburg, Germany Dipartimento ad Attivit a Integrata (DAI) di Patologia e Diagnostica, University of Verona, Verona, Italy Introduction: Pancreatic neuroendocrine tumours are a rare but still very challenging disease, as despite ongoing research, surgical resection still is the only reliable cure. Therefore, about 80 % of patients have a terminal illness and their tumours are still difficult to manage with the currently available chemoand biotherapies obtaining tumour growth stabilization rather than inducing regression. Gene expression analyses of primary tissues from PNET patients identified a number of potential target genes for the development of new therapeutic strategies. Amongst others, we found strong upregulation of the dual specificity kinase TTK, which has been shown before to play an important role during mitosis by inhibiting transition to anaphase until all chromosomes have been attached to the spindle apparatus correctly. Aims: The aim of this study is to elucidate the role of TTK and its value for PNET therapy. Materials & methods: Quantitative realtime PCR, RNAi, cell proliferation and viability assays, Westernblots Results: TTK is strongly overexpressed in pancreatic neuroendocrine tumour tissue. Functional in vitro analyses by siRNA-mediated knockdown of TTK in human as well as in rat PNET cell lines resulted in decreased proliferation and viability of cells, leading to increased apoptosis rates which could be further confirmed by Westernblot analyses of key molecules of the classical apoptosis pathway (Caspase-3 and PARP cleavage). Conclusion: Overexpression of TTK dual specificity kinase in pancreatic neuroendocrine tumours is important for proliferative phenotype of tumour cells and inhibition of TTK leads to apoptotic cell death. Therefore TTK could be a promising target for the treatment of neuroendocrine tumours. Abstract ID: 1416, Oral-3.ID: 1416, Oral-3. Context-dependent epigenetic regulation of NFATc1 transcription in pancreatic plasticity Elisabeth Hessmann , Nai-ming Chen , Clara Lubeseder-Martellato , Jochen Gaedcke , Jens Siveke , Albrecht Neesse , Volker Ellenrieder 1 Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Goettingen, Germany 2 II. Med. Klinikum rechts der Isar, TU Munich, Germany Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, Germany West German Cancer Center Essen, Germany Introduction: Cellular plasticity of the pancreas highly contributes to its enormous regenerative potential upon acinar insults, but also causes therapeutic resistance in pancreatic cancer (PDAC) treatment. On the molecular level, regulation of cellular plasticity involves epigenetic mechanisms that transcriptionally control key-signatures of tissue adaptation. Transcriptional activation of the oncogenic Nuclear Factor of Activated T-cell (NFAT) c1 transcription factor significantly contributes to PDAC cell plasticity. Nevertheless, how epigenetic alterations converge on transcriptional regulation of NFATc1 remains elusive. Aims: To investigate how epigenetic regulation impacts on NFATc1 transcription in pancreatic plasticity. Materials&methods: NFATc1 function and regulationwere studied in the regenerative pancreas upon caerulein-induced acinar cell damage and in various in vitroand in vivo PDAC-models. EZH2-dependency of NFATc1 expression was determined upon genetic or pharmacological EZH2Abstracts / Pancreato S10 inhibition. NFATc1 promoter activity was investigated by ChIP-Assays in pancreatic tissue and cells. Co-expression of EZH2 and NFATc1 was validated in micro-dissected PDAC cells from human samples. Results: Pancreatic tissue regeneration requires silencing of the NFATc1 promoter by the Polycomb-Repressor-Complex member EZH2 to circumvent organ atrophy and exocrine insufficiency. In contrast, EZH2 activation in PDAC shows inverse effects on NFATc1 promoter regulation and promotes PDAC cell plasticity by enhancing NFATc1 transcription. Oncogenic mutation of Kraswas identified as the crucial genetic hit responsible for the functional switch in EZH2-dependent regulation of NFATc1 transcription. Conclusion: These data complement previous descriptions of Polycomb-independent EZH2 functions and emphasize how epigenetic mechanisms integrate into genomic alterations in PDAC. Consequently, pharmacological inhibition of EZH2 represents a beneficial strategy to overcome oncogenic NFATc1 activity in PDAC.

HG-105DEFORMATIONAL CHANGES IN THE HUMAN BRAIN STEM FROM CONVECTION ENHANCED DELIVERY (CED)

HG-105. DEFORMATIONAL CHANGES IN THE HUMAN BRAIN STEM FROM CONVECTION ENHANCED DELIVERY (CED) Karima Tizi1, Eva Wembacher3, Rowena Thomson3, Maria Donzelli2, Elizabeth Vaconcellos3, and Mark Souweidane1,2; Weill Cornell Medical College, New York, NY, USA; Memorial Sloan Kettering Cancer Center, New York, NY, USA; BrainLab, Munich, Germany INTRODUCTION: Preclinical work using CED has minimized concerns regarding conformational alterations in the brain. There has been no volumetric assessments however in humans undergoing CED. As part of an ongoing Phase 1 clinical trial using CED for children with DIPG, we sought to measure any treatment-related volumetric alterations in the human brain stem. METHODS: Volumetric measurements were performed using the pretreatment baseline and the firstpost-treatment MRI scans. An automatedalgorithm based on standard anatomical landmarks and post processing manual correction was used for 3-dimensional rendering of the brain stem. These measurements were longitudinally determined and reported as a percent change. Results were correlated with the assigned dose level and hence infusion volume. RESULTS: Brain stem volumetric assessments were performed in six patients (mean age 1⁄4 9.98 years) treated on two different dose levels (mean infusate volume 1⁄4 2.58 ml and 3.54 ml). At the lower dose level the mean pre-treatment brain stem volumes 1⁄4 45.5 cm3, mean post-treatment volumes 1⁄4 46.3 cm3, and the mean DV 1⁄4 0.876 cm3 (SD 1.74) (2%). At the higher dose level the mean pre-treatment volumes 1⁄4 35.1 cm3, mean posttreatment volumes 1⁄4 39.2 cm3, and the mean DV 1⁄4 4.017 cm3 (SD 1.6) (11.8%). CONCLUSION: CED for children with DIPG results in deformational changes of the brain stem. These volumetric alterations are dosedependent and may have implications in assessment of disease response. Correlation of such volumetric alterations with clinical tolerance may help design future clinical trials that employ CED in the brain stem. Neuro-Oncology 18:iii48–iii77, 2016. doi:10.1093/neuonc/now073.101 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sulfated glycosaminoglycan derivatives affect the bioactivity of angiogenic growth factors

Event Abstract Back to Event Sulfated glycosaminoglycan derivatives affect the bioactivity of angiogenic growth factors Linda Koehler1, Sandra Rother1, Stephanie Moeller2, Matthias Schnabelrauch2, Vera Hintze1 and Dieter Scharnweber1 1 TU Dresden, Max Bergmann Center of Biomaterials, Germany 2 INNOVENT e.V., Biomaterials Department, Germany Introduction: Sulfated glycosaminoglycans (GAGs) are promising candidates for functional bio­ma­terials since their sulfate groups modulate the binding of growth factors, thereby influencing their biological activity profile. The interaction of different GAGs with several growth factors has previously been reported. These stu­dies demonstrated a sulfation- and carbohydrate backbone-dependent binding of GAGs resulting in an influence on the interaction of these mediators with recep­tors and therefore their bioactivity[1],[2]. Angiogenic growth factors, like vascular endothelial (VEGF) and basic fibroblast growth factor (bFGF) play an important role during wound healing[3],[4]. Heparin is known to distinctly regulate VEGF and bFGF signaling by altering their interaction with the respective receptors[4],[5]. Hence we hypothesize that VEGF and bFGF interaction with different GAGs influences their bioactivity depending on their degree of sul­fa­tion (D.S.) and carbohydrate backbone. This might lead to important implications for the use of GAGs as part of biomaterials for controlling angiogenesis during wound healing in health com­pro­mised patients. Materials and Methods: The interaction of VEGF and bFGF with different sulfated hyaluronan (sHA) and chondroitin sulfate (CS) derivatives was determined via surface plasmon resonance (SPR). VEGF or bFGF were im­mobilized onto a sensor chip surface and dif­fe­rent concentrations of solute GAGs were injected to reveal their binding strength. Addi­tionally, ELISA experiments with immobilized GAGs were performed to validate the SPR results. The influence of GAGs on the capability of growth factors to bind to their receptors was again investigated by SPR, while the consequences of the GAG/growth factor interaction on bioactivity were studied in cell-based bioassays. Here pre-incubated GAG/growth factor complexes were added to the cells and growth factor-stimulated cell proliferation was de­termined. Results and Discussion: In case of bFGF the binding strength of sHA and CS derivatives reveals a strong dependence on the D.S. but not on the carbohydrate backbone of the GAG. For VEGF, however, low-sHA and high-sulfated CS showed a comparable bin­ding strength. These results imply that the different molecular geometries in the carbohydrate backbone of the GAGs might render the respec­tive sulfate groups to interact differently. This is further emphasized in investigations with TGF-β1 whe­re naturally sulfated heparin demonstrated a comparable binding strength to high sulfated CS, even though it has a lower D.S[2]. The binding of growth factors to their respective recep­tors was modulated in the presence of GAGs which implies an altered biological profile. This could be verified in cell-based bioassays, since the presence of GAGs affected the growth factor-stimulated proliferation of the cells. Conclusion: The results imply that sulfated GAGs are promising candidates to be included in biomaterial coatings for controlling angiogenesis and therefore wound hea­ling processes, which would in particular be beneficial for health com­pro­mised patients. We acknowledge financial support by the DFG [SFB Transregio 67, projects A2, A3 and Z3].

3D Plotting of thiol-ene cross-linked Polyglycidol hydrogels with hyaluronic acid as transient rheological additive

Event Abstract Back to Event 3D Plotting of thiol-ene cross-linked Polyglycidol hydrogels with hyaluronic acid as transient rheological additive Simone Stichler1, Tomasz Jüngst1 and Jürgen Groll1 1 University of Würzburg, Department of Functional Materials in Medicine and Dentistry, Germany Introduction: Hydrogels are three dimensional (3D) structures in which cells can be encapsulated in an environment which is similar to the extracellular matrix. Suitable hydrogel systems for Tissue Engineering should be biocompatible, biodegradable and the mechanical properties should match those of the desired tissue. With the 3D printing of hydrogel solutions constructs with defined pore sizes can be obtained. Hence the printing of cell-seeded hydrogels enables a higher variability in the field of Tissue Engineering[1]. The focus of our work is on printing of hydrogel solutions based on polyglycidols and hyaluronic acid. This leads to a chemical cross-linked hydrogel construct with defined geometry. Materials and Methods: P(AGE-co-G) was synthesized in bulk according to[2] with addition of AGE monomer for the co-polymerisation. P(AGE-co-G) was afterwards converted to PG-SH and different degrees of functionalization were achieved. To receive the desired hydrogel, thiol-ene click reaction was used for cross-linking. The photochemical introduced reaction (Irgacure 2959, 10 min at 365 nm) occurs between P(AGE-co-G) and PG-SH. Addition of native hyaluronic acid to the hydrogel solution was used to tailor rheological properties of the formulation for printability using dispense plotting. Results and Discussion: After synthesis of the scaffold polymers, optimal polymer ratios and reaction conditions were evaluated. Furthermore precursor solutions were optimized in viscosity by adding additional non-modified hyaluronic acid to achieve printability. Afterwards first cell encapsulation studies were carried out. Conclusion: By combination of the hydrogel system with unmodified hyaluronic acid the solution is printable and hence hierarchical constructs could be obtained. Next steps will focus on optimizing the printing parameters and furthermore on printing of cell-laden hydrogels. We thank the European Union’s Seventh Framework Programme (FP7/2007-2013) for funding under grant agreement no. 309962 (project HydroZONES)

How strontium-substitution of calcium phosphate bone cements affects their resorption by osteoclasts

Event Abstract Back to Event How strontium-substitution of calcium phosphate bone cements affects their resorption by osteoclasts Matthias Schumacher1, Alena S. Wagner2, Julia Kokesch-Himmelreich3, Anne Bernhardt1, Marcus Rohnke3, Sabine Wenisch2 and Michael Gelinsky1 1 Centre for Translational Bone, Joint and Soft Tissue Research, Technische Universität Dresden, Germany 2 Justus-Liebig-University of Giessen, Institute of Veterinary-Anatomy, Germany 3 Justus-Liebig-Universität Giessen, Institute for Physical Chemistry, Germany Introduction: Since strontium was discovered to exert a stimulating effect on the bone turnover[1] a number of approaches have been proposed to obtain Sr-releasing bone cements for the local delivery of therapeutically active Sr-ions into a specific bone defect[2]. However, while the stimulating effect of several cement formulations on bone forming cells has been demonstrated in vitro[3] and some in vivo studies revealed a positive effect of such substitution on bone defect healing, no studies on the osteoclastic resorption of Sr-laden calcium phosphate cements (SrCPC) have been published so far. In this work we demonstrate how SrCPC do not prevent osteoclastogenesis but effectively reduce the osteoclastic resorption activity in vitro which might be beneficial for applications in systemically altered, especially osteoporotic bone lesions. Materials and Methods: SrCPC were obtained by substitution of Ca2+ with Sr2+ via partial or total replacement of CaCO3 by SrCO3 (denoted as S50 and S100, respectively) in an α-TCP based, hydroxyapatite forming cement system (CPC)[3]. Sr-ion release in cell culture media was studied using ICP-MS and the effect of corresponding Sr-concentrations on osteoclast-like cells (OC) obtained from human buffy-coat derived primary monocytes via stimulation with M-CSF and RANKL was studied. Furthermore, cells were directly seeded on SrCPC and analysed with respect to morphology, gene expression (TRAP, Cathepsin K) and enzyme activity of OC markers (TRAP, carbonic anhydrase II) as well as resorption pit formation. Intracellular Sr-concentration was assessed using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Results and Discussion: SrCPC were shown to sustainably release 0.05-0.15 mM strontium depending on the degree of substitution. OC-related enzyme activity was reduced at >0.01 mM strontium, but formation of OC-like cells could be detected up to 1 mM strontium. Accordingly multinucleated, TRAP-positive cells could be found on SrCPC as well as on the Sr-free reference. This is of importance, since the presence of OC in the bone regenerative niche and their expression of paracrine factors is crucial for bone healing. OC-specific gene expression as well as activity of OC marker enzymes was altered, however not uniformly reduced on SrCPC. In contrast, a drastic decrease of resorption activity with increasing strontium content by means of resorption pit formation (Fig. 1A) and diameter (B) could be detected on SrCPC, which could be related to the intracellular uptake of Sr2+ (ToF-SIMS). Figure 1: SEM imaging of resorption pits on CPC and Sr-releasing cements S50 and S100 (A) as well as quantitative evaluation of the resorption pit area (B). Conclusions: In addition to their ability to stimulate bone forming cells[2],[3], SrCPC were shown to reduce the resorption activity, but not the formation of bone resorbing cells in vitro in this work. These findings could help to understand the overall stimulating effect of Sr-releasing cements on bone defect healing. This work was funded by the DFG within the projects M2, M5 and B5 of the SFB Transregio 79.

Hyaluronan-collagen hydrogels support growth of human fibroblasts and are applicable to experimental skin wounds.

Event Abstract Back to Event Hyaluronan-collagen hydrogels support growth of human fibroblasts and are applicable to experimental skin wounds. Stephan Thoenes1, 2, Sandra Rother2, 3, Vanessa Galiazzo2, 3, Jana Becher2, 4, Dieter Scharnweber2, 3, Matthias Schnabelrauch2, 4, Vera Hintze2, 3 and Ulf Anderegg1, 2* 1 Leipzig University, Dept. of Dermatology, Germany 2 Leipzig University, Dresden University, Collaborative Research Center (SFB-TR67) Matrixengineering, Germany 3 Technische Universitaet Dresden, Max Bergmann Center for Biomaterials, Germany 4 INNOVENT e.V., Biomaterials Department, Germany Introduction: Components of the extracellular matrix (ECM) may foster the development of bioinspired, functional biomaterials selectively controlling and promoting skin regeneration. Glycosaminoglycans (GAG) including sulfated hyaluronan (sHA) are attractive starting materials for the generation of skin-compatible scaffolds due to their cytocompatibility, binding capacity for mediator proteins and relatively quick biodegradation. However, manufacturing of stable HA hydrogel scaffolds with reproducible properties and interconnected pores is challenging. A promising approach is the preparation of porous hydrogels from crosslinkable GAG polymers. We developed and characterized photo-crosslinked hydrogels made of acrylated HA, acrylated and sulfated HA and collagen and demonstrated the biological compatibility for the culture of primary dermal fibroblasts (Fb) in vitro and in vivo with the perspective to develop a scaffold material for dermal wound treatment. Materials and Methods: Low molecular weight HA, and sulfated HA (sHA) were acrylated as described by Becher et al[1]. using phase transfer conditions. For hydrogel formation acrylated GAGs, collagen type I and photo-initiator lithium phenyl-2,4,6-trimethyl-benzoylphosphinate solutions were mixed, applied to silicon molds and cross-linked by UV light followed by freeze drying and washing. The resulting hydrogels were characterized regarding their composition, release behavior, morphology, mechanical and swelling properties. For biological testing the hydrogels were seeded with human foreskin and mouse skin Fb. Attachment, seeding efficiency and survival, gel penetration and matrix deposition were investigated in vitro. Furthermore, pre-seeded and cell-free hydrogels were applied to full thickness wounds of mouse skin. After 7 days the hydrogels and wound tissue were removed and analyzed with respect to cell and matrix content. Results and Discussion: Hydrogels containing HA or HA combined with sHA as well as fibrillar collagen type I displayed a reproducible stable structure, high porosity after freeze drying with pores larger than 100 µm and good swelling properties adsorbing the maximum of water within 5 minutes. Desorption experiments over 8 days at 37°C proved a small release of sulfated GAGs, while the loss of collagen was higher. An effective seeding procedure enabling the growth of human Fb for at least 12 days was established. Fb settled the hydrogels completely (up to 600 µm) and deposited their own matrix. The hydrogels enabled cellular survival for up to 7 days when applied to full thickness wounds and either pre-seeded with mouse dermal Fb or used as empty scaffolds, suggesting good biocompatibility in vivo as well. Conclusions: Hydrogels prepared from acrylated HA, sulfated GAGs and fibrillar collagen are effective substrates for Fb in vitro and in vivo. Cells can growth within these gels, proliferate and deposit their own matrix within the pores. Taken together, HA-and hsHA-based hydrogels are promising biomaterials for the development of skin equivalents incorporating cells, bioactive mediators or modified GAG components. The authors would like to thank the DFG (TRR 67, subprojects A2, A3, B4, Z3) for financial support.

On the role of heparin and integrin binding segments in cell adhesion of biomaterials

Event Abstract Back to Event On the role of heparin and integrin binding segments in cell adhesion of biomaterials Franziska Dreher1*, Mareen Pagel1* and Annette G. Beck-Sickinger1* 1 Universität Leipzig, Faculty of Biochemistry, Pharmacy and Psychology, Institute forBiochemistry, Germany Introduction: In order to improve functional biomaterials multifunctional coating is suggested. By using specific peptide sequences to mimic proteins of the extracellular matrix of the bone new approaches for improved implant integration have been suggested. Materials and Methods: The integrin binding sequence (c[RGDfK]) and a heparin binding sequence (FHRRIKA) were immobilized on titanium binding peptides. Cell adhesion, spreading, viability and proliferation of MG-63 cells on c[RGDfK] and FHRRIKA itself, in a combined peptide and in a 1:1 mixture were investigated in comparison to blank titanium, the titanium binding peptide itself and surface coating with fibronectin (FN). Results and Discussion: Only c[RGDfK] alone could markedly increase the number of adherent cells comparable to the level of FN, while cell spreading was elevated by all cell binding motifs. Hereby, c[RGDfK] and FHRRIKA itself and in a 1:1 mixture enhanced cell spreading to the same extend, while the combination of both motifs in one molecule increased cell size additionally. The coating combining c[RGDfK] and FHRRIKA also significantly increased cell viability compared to blank titanium. Viability was even higher than of FN, c[RGDfK] and FHRRIKA coating surfaces. Cell proliferation was generally enhanced on titanium compared to the tissue culture plate, but showed no significant differences with respect to the cell binding motif. Conclusion: These results demonstrate that short peptide sequences containing integrin and heparin binding motifs can efficiently enhance cell surface interactions on titanium and synergistically improve cell spreading and viability in MG-63 cells. TRR67/A4 Keywords: Bone Regeneration, Cell Adhesion, Biomimetic, RGD peptide Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Adhesive biomaterials Citation: Dreher F, Pagel M and Beck-Sickinger AG (2016). On the role of heparin and integrin binding segments in cell adhesion of biomaterials. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01960 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Franziska Dreher, Universität Leipzig, Faculty of Biochemistry, Pharmacy and Psychology, Institute forBiochemistry, Leipzig, Germany, Email1 Dr. Mareen Pagel, Universität Leipzig, Faculty of Biochemistry, Pharmacy and Psychology, Institute forBiochemistry, Leipzig, Germany, Email2 Dr. Annette G Beck-Sickinger, Universität Leipzig, Faculty of Biochemistry, Pharmacy and Psychology, Institute forBiochemistry, Leipzig, Germany, Email3 Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Franziska Dreher Mareen Pagel Annette G Beck-Sickinger Google Franziska Dreher Mareen Pagel Annette G Beck-Sickinger Google Scholar Franziska Dreher Mareen Pagel Annette G Beck-Sickinger PubMed Franziska Dreher Mareen Pagel Annette G Beck-Sickinger Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Development of nano electrodes for cell/tissue stimulation

Event Abstract Back to Event Development of nano electrodes for cell/tissue stimulation Tobias Weigel1, Jihyoung Choi1, Tobias Schmitz1, Maren Jannasch1, Sabine Gätzner1 and Jan Hansmann1 1 University Hospital of Wuerzburg, Tissue Engineering & Regenerative Medicine, Germany Introduction: A central challenge of current tissue electrodes is a high energy consumption caused by inefficient electrical stimulation of the objective cells. Leakage currents, the distance between electrode and target cells as well as the encapsulation of the electrode through the foreign body reaction (FBR) are reasons for this. In our study, nano structured electrodes are developed to optimize the energy transfer at the interface between electrode and cell/tissue. Therefore, conductive electrospun scaffolds with different dimensions and structures are generated, to identify an ideal electrode interaction with cells and tissue. Materials and Methods: The conductive nano fibers were generated by electrospinning of a polyacrylonitrile (PAN) solution with different fiber orientations, diameters and pores. Through an oxidation step and subsequent carbonization, the PAN fibers were converted to carbon fibers. Additionally the nano fibers are nano structured with graphene or other carbonaceous materials by salt melt synthesis (SMS). The properties of the fibers were characterized by SEM and Raman, as well as the electrical conductivity and impedance. Biocompatibility and cell interaction was investigated with human fibroblasts. The electrical stimulation characteristics were tested with cardio muscle stripes in a myograph integrated organ bath. Results: The carbon nano fibers for the cell test exhibited a diameter of about 140, 290 and 530 nm. While the 140 nm fibers are completely disorientated, the other fibers showed a preferred orientation. The conductivity of the fibers was approximately 150 S/cm. Carbonaceous functionalized fibers showed a doubled conductivity and increased tear strength. Contact angle measurements, impedance spectroscopy and protein adsorption assays demonstrated interaction of the nano fibers with the cell culture medium. Cell culture studies using human fibroblasts could demonstrate varying reactions to the different fiber morphologies. Furthermore the generated electrodes were instituted to simulate the energy consumption with human cardio muscle stripes. First results showed a comparable or lower energy expenditure of the nano fibers electrodes compared to commercial electrodes. Discussion: The electrical and mechanical improvement of the carbon fibers is achieved by wrapping and interconnecting with carbonaceous materials. Tests with fibroblasts showed an increased ingrowth into the fiber matrix with higher pore diameter. Additionally released cytokines are measured to compare the different nano fiber structures. Keywords: nanofiber, electric, biomedical application, bioinerface Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biocompatibility of nanobiomaterials Citation: Weigel T, Choi J, Schmitz T, Jannasch M, Gätzner S and Hansmann J (2016). Development of nano electrodes for cell/tissue stimulation. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02212 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Tobias Weigel Jihyoung Choi Tobias Schmitz Maren Jannasch Sabine Gätzner Jan Hansmann Google Tobias Weigel Jihyoung Choi Tobias Schmitz Maren Jannasch Sabine Gätzner Jan Hansmann Google Scholar Tobias Weigel Jihyoung Choi Tobias Schmitz Maren Jannasch Sabine Gätzner Jan Hansmann PubMed Tobias Weigel Jihyoung Choi Tobias Schmitz Maren Jannasch Sabine Gätzner Jan Hansmann Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A composite approach: adapting emulsion templated polymers for use in bone tissue engineering

Event Abstract Back to Event A composite approach: adapting emulsion templated polymers for use in bone tissue engineering Aaron Z. Lee1, 2, Caitlin R. Langford1, Luis M. Rodriguez-Lorenzo3, 4, Oliver Bissinger5, Helmut Thissen2 and Neil R. Cameron1 1 Monash University, Materials Science and Engineering, Australia 2 Commonwealth Scientific and Industrial Research Organisation, Manufacturing Flagship, Australia 3 ICTP-CSIC, Polymeric Nanomaterials and Biomaterials, Spain 4 CIBER-BBN, Polymeric biomateriaasl group, Spain 5 Technical University of Munich, Oral and Maxillofacial Surgery, Germany Introduction: Synthetic scaffolds are envisioned as potential medical devices capable of aiding in the repair and regeneration of host tissues. Templating based on high internal phase emulsions represents a versatile route to the creation of highly porous architectures capable of supporting cell in growth. Recent developments include the use of click chemistry and surface functionalisation to tailor the presented environment towards a given application[1]. The current work investigates the formation of a polymer composite material based on the combination of an emulsion templated polymer in conjunction with hydroxyapatite for use in bone tissue engineering. Fabricated materials were physically characterised and evaluated for biocompatibility through in vitro culture of MG63 osteosarcoma cells. Materials and Methods: A monomer mixture consisting of a trithiol [trimethylopropane tris(3-mercaptopropionate)] and a multifunctional acrylate [dipentaerythritol penta/hexa-acrylate] dissolved in 1,2-dichloroethane with Hypermer B246 as the surfactant was used to form the polymer network. Photoinitiator was added to the mixture before adding water dropwise to a total volume of 140mL. Hydroxyapatite nanoparticles were incorporated into the monomer phase and dispersed before the addition of water. Emulsions were subsequently cured by exposure to UV irradiation to form the polyHIPE. Materials were characterised by FTIR. In vitro cell culture was performed on 200μm thick sections against Alvetex® with an initial seeding density of 0.5x106 cells and cultured in DMEM + 10%FBS for up to 21 days. Samples were then fixed and stained using histological techniques. Results and Discussion: Comparison between the FTIR spectra of the polyHIPE materials allowed evaluation of the incorporation of hydroxyapatite. Notably, this is evinced through the appearance of the peaks at 568cm-1 and 1030cm-1 in the composite which correspond directly to key peaks in the spectra for hydroxyapatite. Alvetex® scaffolds, based on polystyrene, were used as control substrates to evaluate the suitability of the culture conditions. No significant adverse effects were observed on this substrate or the native polyHIPE, and both supported cell attachment and growth for the duration of the culture period. At early time points, von Kossa staining experiments showed staining of the polyHIPE + 5wt% hydroxyapatite scaffolds. Even staining was observed albeit with darker regions corresponding to particle agglomerates. After 21 days in culture, the staining pattern changed dramatically with intense clusters being observed in the space taken up by cells while the uptake of stain in the scaffold itself was diminished. Ergo, the hydroxyapatite incorporated into the polyHIPE is available for redistribution by cells, potentially accelerating mineralisation. Conclusion: By dispersing hydroxyapatite through the monomer phase, it was possible to generate composite polyHIPE materials which retained their morphology while modulating the biological response. This provides another avenue for the modular design of polyHIPEs for biomaterial applications. Monash University; CSIRO