Year 2020

By year:[ 2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 ]

Kyndiah, A., Leonardi, F., Tarantino, C., Cramer, T., Millan-Solsona, R., Garreta, E., Montserrat, N., Mas-Torrent, M., Gomila, G., (2020). Bioelectronic recordings of cardiomyocytes with accumulation mode electrolyte gated organic field effect transistors Biosensors and Bioelectronics 150, 111844

Organic electronic materials offer an untapped potential for novel tools for low-invasive electrophysiological recording and stimulation devices. Such materials combine semiconducting properties with tailored surface chemistry, elastic mechanical properties and chemical stability in water. In this work, we investigate solution processed Electrolyte Gated Organic Field Effect Transistors (EGOFETs) based on a small molecule semiconductor. We demonstrate that EGOFETs based on a blend of soluble organic semiconductor 2,8-Difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene (diF-TES-ADT) combined with an insulating polymer show excellent sensitivity and long-term recording under electrophysiological applications. Our devices can stably record the extracellular potential of human pluripotent stem cell derived cardiomyocyte cells (hPSCs-CMs) for several weeks. In addition, cytotoxicity tests of pharmaceutical drugs, such as Norepinephrine and Verapamil was achieved with excellent sensitivity. This work demonstrates that organic transistors based on organic blends are excellent bioelectronics transducer for extracellular electrical recording of excitable cells and tissues thus providing a valid alternative to electrochemical transistors.

Keywords: Bioelectronics, Cardiac cells, Organic electronics, Organic field effect transistors, Organic semiconducting blend

Maier, Martina, Ballester, Belén Rubio, Leiva Bañuelos, Nuria, Duarte Oller, Esther, Verschure, P., (2020). Adaptive conjunctive cognitive training (ACCT) in virtual reality for chronic stroke patients: a randomized controlled pilot trial Journal of NeuroEngineering and Rehabilitation 17, (1), 42

Current evidence for the effectiveness of post-stroke cognitive rehabilitation is weak, possibly due to two reasons. First, patients typically express cognitive deficits in several domains. Therapies focusing on specific cognitive deficits might not address their interrelated neurological nature. Second, co-occurring psychological problems are often neglected or not diagnosed, although post-stroke depression is common and related to cognitive deficits. This pilot trial aims to test a rehabilitation program in virtual reality that trains various cognitive domains in conjunction, by adapting to the patient’s disability and while investigating the influence of comorbidities.

Madrid-Gambin, Francisco, Oller-Moreno, Sergio, Fernandez, Luis, Bartova, Simona, Giner, Maria Pilar, Joyce, Christopher, Ferraro, Francesco, Montoliu, Ivan, Moco, Sofia, Marco, Santiago, (2020). AlpsNMR: an R package for signal processing of fully untargeted NMR-based metabolomics Bioinformatics revisar (no pdf) no en web general, revisar (no pdf) no en web general

NMR-based metabolomics is widely used to obtain metabolic fingerprints of biological systems. While targeted workflows require previous knowledge of metabolites, prior to statistical analysis, untargeted approaches remain a challenge. Computational tools dealing with fully untargeted NMR-based metabolomics are still scarce or not user-friendly. Therefore, we developed AlpsNMR (Automated spectraL Processing System for NMR), an R package that provides automated and efficient signal processing for untargeted NMR metabolomics. AlpsNMR includes spectra loading, metadata handling, automated outlier detection, spectra alignment and peak-picking, integration, and normalization. The resulting output can be used for further statistical analysis. AlpsNMR proved effective in detecting metabolite changes in a test case. The tool allows less experienced users to easily implement this workflow from spectra to a ready-to-use dataset in their routines.The AlpsNMR R package and tutorial is freely available to download from under the MIT license.

Wang, Lei, Song, Shidong, van Hest, Jan, Abdelmohsen, Loai K. E. A., Huang, Xin, Sánchez, Samuel, (2020). Biomimicry of cellular motility and communication based on synthetic soft-architectures Small ahead, 1907680

Cells, sophisticated membrane‐bound units that contain the fundamental molecules of life, provide a precious library for inspiration and motivation for both society and academia. Scientists from various disciplines have made great endeavors toward the understanding of the cellular evolution by engineering artificial counterparts (protocells) that mimic or initiate structural or functional cellular aspects. In this regard, several works have discussed possible building blocks, designs, functions, or dynamics that can be applied to achieve this goal. Although great progress has been made, fundamental—yet complex—behaviors such as cellular communication, responsiveness to environmental cues, and motility remain a challenge, yet to be resolved. Herein, recent efforts toward utilizing soft systems for cellular mimicry are summarized—following the main outline of cellular evolution, from basic compartmentalization, and biological reactions for energy production, to motility and communicative behaviors between artificial cell communities or between artificial and natural cell communities. Finally, the current challenges and future perspectives in the field are discussed, hoping to inspire more future research and to help the further advancement of this field.

Nonaka, P. N., Falcones, B., Farre, R., Artigas, A., Almendros, I., Navajas, D., (2020). Biophysically preconditioning mesenchymal stem cells improves treatment of ventilator-induced lung injury Archivos de Bronconeumología Archivos de Bronconeumologia , In press

Klein, L. M., Chang, J., Gu, W., Manekeller, S., Jansen, C., Lingohr, P., Praktiknjo, M., Kalf, J. C., Schulz, M., Spengler, U., Strassburg, C., Cárdenas, A., Arroyo, V., Trebicka, J., (2020). The development and outcome of acute-on-chronic liver failure after surgical interventions Liver Transplantation 26, (2), 227-237

Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality. Precipitating events, including hemorrhage and infections, contribute to ACLF development, but the role of surgery remains unknown. We investigated the development of ACLF in patients with cirrhosis undergoing surgery. In total, 369 patients with cirrhosis were included in the study. The clinical and laboratory data were collected prior to and on days 1-2, 3-8, and 9-28, and at 3 and 12 months after surgery. Surgery type was classified as limited or extensive, as well as liver and nonliver surgery. A total of 39 patients had baseline ACLF. Surgery was performed during acute decompensation in 35% of the rest of the 330 patients, and 81 (24.5%) developed ACLF within 28 days after surgery. Surrogate markers of systemic inflammation were similar in patients who developed ACLF or not. Age, sex, serum sodium, baseline bacterial infection, and abdominal nonliver surgery were independent predictors for the development of ACLF after surgery. Patients who developed ACLF within 28 days after surgery had a higher mortality at 3, 6, and 12 months. Survival did not differ between patients with ACLF at surgery and those developing ACLF after surgery. Development of ACLF within 28 days after surgery and elevated alkaline phosphatase and international normalized ratio were independent predictors of 90-day mortality. Independent predictors of 1-year all-cause mortality were alkaline phosphatase, Model for End-Stage Liver Disease score, and preoperative hepatic encephalopathy, whereas nonliver surgery was associated with improved survival. ACLF frequently develops in patients with cirrhosis undergoing surgery, especially in those with active bacterial infection, lower serum sodium, and kidney or coagulation dysfunction. Prognoses of ACLF both at and after surgery are similarly poor. Patients with cirrhosis should be carefully managed perioperatively.

Fabregas, R., Gomila, G., (2020). Dielectric nanotomography based on electrostatic force microscopy: A numerical analysis Journal of Applied Physics 127, (2), 024301

Electrostatic force microscopy (EFM) can image nanoscale objects buried below the surface. Here, we theoretically show that this capability can be used to obtain nanotomographic information, i.e., the physical dimensions and dielectric properties, of buried nano-objects. These results constitute a first step toward implementing a nondestructive dielectric nanotomography technique based on EFM with applications in materials sciences and life sciences.

Marafon, G., Moretto, A., Zanuy, D., Alemán, C., Crisma, M., Toniolo, C., (2020). Effect on the conformation of a terminally blocked, (E) β,γ-unsaturated δ-amino acid residue induced by carbon methylation Journal of Organic Chemistry 85, (3), 1513-1524

Peptides are well-known to play a fundamental therapeutic role and to represent building blocks for numerous useful biomaterials. Stabilizing their active 3D-structure by appropriate modifications remains, however, a challenge. In this study, we have expanded the available literature information on the conformational propensities of a promising backbone change of a terminally blocked δ-amino acid residue, a dipeptide mimic, by replacing its central amide moiety with an (E) Cβ═Cγ alkene unit. Specifically, we have examined by DFT calculations, X-ray diffraction in the crystalline state, and FT-IR absorption/NMR spectroscopies in solution the extended vs folded preferences of analogues of this prototype system either unmodified or possessing single or multiple methyl group substituents on each of its four −CH2-CH═CH-CH2– main-chain carbon atoms. The theoretical and experimental results obtained clearly point to the conclusion that increasing the number of adequately positioned methylations will enhance the preference of the original sequence to fold, thus opening interesting perspectives in the design of conformationally constrained peptidomimetics.

Minguela, J., Slawik, S., Mücklich, F., Ginebra, M. P., Llanes, L., Mas-Moruno, C., Roa, J. J., (2020). Evolution of microstructure and residual stresses in gradually ground/polished 3Y-TZP Journal of the European Ceramic Society In press

A comprehensive study of progressively ground/polished 3Y-TZP was performed with the aim of better understanding the mechanisms driving the microstructural modifications observed after such procedures, and identifying the processing parameters leading to optimal microstructures (i.e. ageing-protective and damage-free). Gradually ground/polished surfaces were produced, yielding four different topographies of increasing roughness (grades 1–4) and two different textures (unidirectionally, U, and multidirectionally, M). Phase transformation, microstructure and residual stresses were investigated by means of advanced characterization techniques. It was found that low-roughness mildly ground/polished specimens (i.e. 2-M/U) presented a nanometric layer with the ageing-related protective features generally associated with coarsely ground specimens. A lower limit for grain refinement in terms of surface abrasion was also found, in which partial recrystallization took place (i.e. 1-M/U). A mathematical relation was established between average surface roughness (Sa), monoclinic volume fraction (Vm) and surface compressive residual stresses, demonstrating that if the processing parameters are controlled, both Vm and residual stresses can be predicted by the measurement of Sa.

Keywords: Grinding, Microstructure, Phase transformation, Residual stresses, Zirconia

Donnelly, Joanna L., Offenbartl-Stiegert, Daniel, Marín-Beloqui, José M., Rizzello, Loris, Battaglia, Guiseppe, Clarke, Tracey M., Howorka, Stefan, Wilden, Jonathan D., (2020). Exploring the relationship between BODIPY structure and spectroscopic properties to design fluorophores for bioimaging Chemistry - A European Journal 26, (4), 863-872

Designing chromophores for biological applications requires a fundamental understanding of how the chemical structure of a chromophore influences its photophysical properties. We here describe the synthesis of a library of BODIPY dyes, exploring diversity at various positions around the BODIPY core. The results show that the nature and position of substituents have a dramatic effect on the spectroscopic properties. Substituting in a heavy atom or adjusting the size and orientation of a conjugated system provides a means of altering the spectroscopic profiles with high precision. The insight from the structure–activity relationship was applied to devise a new BODIPY dye with rationally designed photochemical properties including absorption towards the near-infrared region. The dye also exhibited switch-on fluorescence to enable visualisation of cells with high signal-to-noise ratio without washing-out of unbound dye. The BODIPY-based probe is non-cytotoxic and compatible with staining procedures including cell fixation and immunofluorescence microscopy.

Park, D., Wershof, E., Boeing, S., Labernadie, A., Jenkins, R. P., George, S., Trepat, X., Bates, P. A., Sahai, E., (2020). Extracellular matrix anisotropy is determined by TFAP2C-dependent regulation of cell collisions Nature Materials Article in Press

The isotropic or anisotropic organization of biological extracellular matrices has important consequences for tissue function. We study emergent anisotropy using fibroblasts that generate varying degrees of matrix alignment from uniform starting conditions. This reveals that the early migratory paths of fibroblasts are correlated with subsequent matrix organization. Combined experimentation and adaptation of Vicsek modelling demonstrates that the reorientation of cells relative to each other following collision plays a role in generating matrix anisotropy. We term this behaviour ‘cell collision guidance’. The transcription factor TFAP2C regulates cell collision guidance in part by controlling the expression of RND3. RND3 localizes to cell–cell collision zones where it downregulates actomyosin activity. Cell collision guidance fails without this mechanism in place, leading to isotropic matrix generation. The cross-referencing of alignment and TFAP2C gene expression signatures against existing datasets enables the identification and validation of several classes of pharmacological agents that disrupt matrix anisotropy.

Keywords: Biomaterials – cells, Cell migration, Self-assembly, Tissues

Burgués, Javier, Marco, Santiago, (2020). Feature extraction for transient chemical sensor signals in response to turbulent plumes: Application to chemical source distance prediction Sensors and Actuators B: Chemical In press, 128235

This paper describes the design of a linear phase low-pass differentiator filter with a finite impulse response (FIR) for extracting transient features of gas sensor signals (the so-called “bouts”). The detection of these bouts is relevant for estimating the distance of a gas source in a turbulent plume. Our current proposal addresses the shortcomings of previous ‘bout’ estimation methods, namely: (i) they were based in non-causal digital filters precluding real time operation, (ii) they used non-linear phase filters leading to waveform distortions and (iii) the smoothing action was achieved by two filters in cascade, precluding an easy tuning of filter performance. The presented method is based on a low-pass FIR differentiator, plus proper post-processing, allowing easy algorithmic implementation for real-time robotic exploration. Linear phase filters preserve signal waveform in the bandpass region for maximum reliability concerning both ‘bout’ detection and amplitude estimation. As a case study, we apply the proposed filter to predict the source distance from recordings obtained with metal oxide (MOX) gas sensors in a wind tunnel. We first perform a joint optimization of the cut-off frequency of the filter and the bout amplitude threshold, for different wind speeds, uncovering interesting relationships between these two parameters. We demonstrate that certain combinations of parameters can reduce the prediction error to 8 cm (in a distance range of 1.45 m) improving previously reported performances in the same dataset by a factor of 2.5. These results are benchmarked against traditional source distance estimators such as the mean, variance and maximum of the response. We also study how the length of the measurement window affects the performance of different signal features, and how to select the filter parameters to make the predictive models more robust to changes in wind speed. Finally, we provide a MATLAB implementation of the bout detection algorithm and all analysis code used in this study.

Keywords: Gas sensors, Differentiator, Low pass filter, Metal oxide semiconductor, MOX sensors, Signal processing, Feature extraction, Gas source localization, Robotics

Sánchez-Fibla, M., Forestier, S., Moulin-Frier, C., Puigbò, J. Y., Verschure, P., (2020). From motor to visually guided bimanual affordance learning Adaptive Behavior Article first published online

The mechanisms of how the brain orchestrates multi-limb joint action have yet to be elucidated and few computational sensorimotor (SM) learning approaches have dealt with the problem of acquiring bimanual affordances. We propose a series of bidirectional (forward/inverse) SM maps and its associated learning processes that generalize from uni- to bimanual interaction (and affordances) naturally, reinforcing the motor equivalence property. The SM maps range from a SM nature to a solely sensory one: full body control, delta SM control (through small action changes), delta sensory co-variation (how body-related perceptual cues covariate with object-related ones). We make several contributions on how these SM maps are learned: (1) Context and Behavior-Based Babbling: generalizing goal babbling to the interleaving of absolute and local goals including guidance of reflexive behaviors; (2) Event-Based Learning: learning steps are driven by visual, haptic events; and (3) Affordance Gradients: the vectorial field gradients in which an object can be manipulated. Our modeling of bimanual affordances is in line with current robotic research in forward visuomotor mappings and visual servoing, enforces the motor equivalence property, and is also consistent with neurophysiological findings like the multiplicative encoding scheme.

Keywords: Affordances, Bimanual affordances, Goal babbling, Interlimb coordination, Motor equivalence, Sensorimotor learning

Burgués, Javier, Hernández, Victor, Lilienthal, Achim J., Marco, Santiago, (2020). Gas distribution mapping and source localization using a 3D grid of metal oxide semiconductor sensors Sensors and Actuators B: Chemical 304, 127309

The difficulty to obtain ground truth (i.e. empirical evidence) about how a gas disperses in an environment is one of the major hurdles in the field of mobile robotic olfaction (MRO), impairing our ability to develop efficient gas source localization strategies and to validate gas distribution maps produced by autonomous mobile robots. Previous ground truth measurements of gas dispersion have been mostly based on expensive tracer optical methods or 2D chemical sensor grids deployed only at ground level. With the ever-increasing trend towards gas-sensitive aerial robots, 3D measurements of gas dispersion become necessary to characterize the environment these platforms can explore. This paper presents ten different experiments performed with a 3D grid of 27 metal oxide semiconductor (MOX) sensors to visualize the temporal evolution of gas distribution produced by an evaporating ethanol source placed at different locations in an office room, including variations in height, release rate and air flow. We also studied which features of the MOX sensor signals are optimal for predicting the source location, considering different lengths of the measurement window. We found strongly time-varying and counter-intuitive gas distribution patterns that disprove some assumptions commonly held in the MRO field, such as that heavy gases disperse along ground level. Correspondingly, ground-level gas distributions were rarely useful for localizing the gas source and elevated measurements were much more informative. We make the dataset and the code publicly available to enable the community to develop, validate, and compare new approaches related to gas sensing in complex environments.

Keywords: Mobile robotic olfaction, Metal oxide gas sensors, Signal processing, Sensor networks, Gas source localization, Gas distribution mapping

Pedraz, Lucas, Blanco-Cabra, Núria, Torrents, Eduard, (2020). Gradual adaptation of facultative anaerobic pathogens to microaerobic and anaerobic conditions The FASEB Journal 34, (2), 2912-2928

Many notable human pathogens are facultative anaerobes. These pathogens exhibit redundant metabolic pathways and a whole array of regulatory systems to adapt to changing oxygen levels. However, our knowledge of facultative anaerobic pathogens is mostly based on fully aerobic or anaerobic cultures, which does not reflect real infection conditions, while the microaerobic range remains understudied. Here, we examine the behavior of pathogenic and nonpathogenic strains of two facultative anaerobes, Escherichia coli and Pseudomonas aeruginosa, during the aerobic-anaerobic transition. To do so, we introduce a new technique named AnaeroTrans, in which we allow self-consumption of oxygen by steady-state cultures and monitor the system by measuring the gas-phase oxygen concentration. We explore the different behavior of the studied species toward oxygen and examine how this behavior is associated with the targeted infection sites. As a model, we characterize the adaptation profile of the ribonucleotide reductase network, a complex oxygen-dependent enzymatic system responsible for the generation of the deoxyribonucleotides. We also explore the actions of the most important anaerobic regulators and how these regulators influence bacterial fitness. Our results allow us to classify the different elements that compose the aerobic-anaerobic transition into reproducible stages, thus showing the different adaptation mechanisms of the studied species.

Santos-Pata, Diogo, Ballester, Belen Rubio, Zucca, Riccardo, Filho, Carlos Stefano, Almeida, Sara Regina, Min, Li Li, Castellano, Gabriela, Verschure, P., (2020). Human CA1 and subiculum activity forecast stroke chronicity medRxiv ahead (pre-print - not valid)

Following a stroke, the brain undergoes a process of neuronal reorganization to compensate for structural damage and cope with functionality loss. Increases in stroke-induced neurogenesis rates in the dentate gyrus and neural migration from the hippocampus towards the affected site have been observed, suggesting that the hippocampus is involved in functionality gains and neural reorganization. Despite the observed hippocampal contributions to structural changes, the hippocampal physiology for stroke recovery has been poorly characterized. To this end, we measured resting-state whole-brain activity from non-hippocampal stroke survivors (n=13) during functional MRI scanning. Analysis of multiple hippocampal subregions revealed that the voxel activity of hippocampal readout sites (CA1 and subiculum) forecast the patient's chronicity stage stronger than early regions of the hippocampal circuit. Furthermore, we observed hemispheric-specific contributions to chronicity forecasting, raising the hypothesis that left and right hippocampus are functionally dissociable during recovery. In addition, we suggest that in contrast with whole-brain analysis, the monitoring of segregated and specialized sub-networks after stroke potentially reveals detailed aspects of stroke recovery. Altogether, our results shed light on the contribution of the subcortical-cortical interplay for neural reorganization and highlight new avenues for stroke rehabilitation.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis project has received funding from the European Union's H2020-EU research and innovation programme under grant agreement ID: 826421Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData will be made public upon article acceptance.

Pijpers, Imke A. B., Cao, Shoupeng, Llopis-Lorente, Antoni, Zhu, Jianzhi, Song, Shidong, Joosten, Rick R. M., Meng, Fenghua, Friedrich, Heiner, Williams, David S., Sánchez, Samuel, van Hest, Jan C. M., Abdelmohsen, Loai K. E. A., (2020). Hybrid biodegradable nanomotors through compartmentalized synthesis Nano Letters ahead

Designer particles that are embued with nanomachinery for autonomous motion have great potential for biomedical applications; however, their development is highly demanding with respect to biodegradability/compatibility. Previously, biodegradable propulsive machinery based on enzymes has been presented. However, enzymes are highly susceptible to proteolysis and deactivation in biological milieu. Biodegradable hybrid nanomotors powered by catalytic inorganic nanoparticles provide a proteolytically stable alternative to those based upon enzymes. Herein we describe the assembly of hybrid biodegradable nanomotors capable of transducing chemical energy into motion. Such nanomotors are constructed through a process of compartmentalized synthesis of inorganic MnO2 nanoparticles (MnPs) within the cavity of organic stomatocytes. We show that the nanomotors remain active in cellular environments and do not compromise cell viability. Effective tumor penetration of hybrid nanomotors is also demonstrated in proof-of-principle experiments. Overall, this work represents a new prospect for engineering of nanomotors that can retain their functionality within biological contexts.

Vila, A., Torras, N., Castaño, Albert G., García-Díaz, María, Comelles, Jordi, Pérez-Berezo, T., Corregidor, C., Castaño, O., Engel, E., Fernández-Majada, Vanesa, Martínez, Elena, (2020). Hydrogel co-networks of gelatine methacrylate and poly(ethylene glycol) diacrylate sustain 3D functional in vitro models of intestinal mucosa Biofabrication Accepted Manuscript

Mounting evidence supports the importance of the intestinal epithelial barrier and its permeability both in physiological and pathological conditions. Conventional in vitro models to evaluate intestinal permeability rely on the formation of tightly packed epithelial monolayers grown on hard substrates. These two-dimensional (2D) models lack the cellular and mechanical components of the non-epithelial compartment of the intestinal barrier, the stroma, which are key contributors to the barrier permeability in vivo. Thus, advanced in vitro models approaching the in vivo tissue composition are fundamental to improve precision in drug absorption predictions, to provide a better understanding of the intestinal biology, and to faithfully represent related diseases. Here, we generate photo-crosslinked gelatine methacrylate (GelMA) - poly(ethylene glycol) diacrylate (PEGDA) hydrogel co-networks that provide the required mechanical and biochemical features to mimic both the epithelial and stromal compartments of the intestinal mucosa, i.e., they are soft, cell adhesive and cell-loading friendly, and suitable for long-term culturing. We show that fibroblasts can be embedded in the GelMA-PEGDA hydrogels while epithelial cells can grow on top to form a mature epithelial monolayer that exhibits barrier properties which closely mimic those of the intestinal barrier in vivo, as shown by the physiologically relevant transepithelial electrical resistance (TEER) and permeability values. The presence of fibroblasts in the artificial stroma compartment accelerates the formation of the epithelial monolayer and boosts the recovery of the epithelial integrity upon temporary barrier disruption, demonstrating that our system is capable of successfully reproducing the interaction between different cellular compartments. As such, our hydrogel co-networks offer a technologically simple yet sophisticated approach to produce functional three-dimensional (3D) in vitro models of epithelial barriers with epithelial and stromal cells arranged in a spatially relevant manner and near-physiological functionality.

Altay, Gizem, Tosi, Sébastien, García-Díaz, María, Martínez, Elena, (2020). Imaging the cell morphological response to 3D topography and curvature in engineered intestinal tissues Frontiers in Bioengineering and Biotechnology 8, 294

While conventional cell culture methodologies have relied on flat, two-dimensional cell monolayers, three-dimensional engineered tissues are becoming increasingly popular. Often, engineered tissues can mimic the complex architecture of native tissues, leading to advancements in reproducing physiological functional properties. In particular, engineered intestinal tissues often use hydrogels to mimic villi structures. These finger-like protrusions of a few hundred microns in height have a well-defined topography and curvature. Here, we examined the cell morphological response to these villus-like microstructures at single-cell resolution using a novel embedding method that allows for the histological processing of these delicate hydrogel structures. We demonstrated that by using photopolymerisable poly(ethylene) glycol as an embedding medium, the villus-like microstructures were successfully preserved after sectioning with vibratome or cryotome. Moreover, high-resolution imaging of these sections revealed that cell morphology, nuclei orientation, and the expression of epithelial polarization markers were spatially encoded along the vertical axis of the villus-like microstructures and that this cell morphological response was dramatically affected by the substrate curvature. These findings, which are in good agreement with the data reported for in vivo experiments on the native tissue, are likely to be the origin of more physiologically relevant barrier properties of engineered intestinal tissues when compared with standard monolayer cultures. By showcasing this example, we anticipate that the novel histological embedding procedure will have a positive impact on the study of epithelial cell behavior on three-dimensional substrates in both physiological and pathological situations.

Keywords: Hydrogel scaffold, Confocal microscopy, Substrate curvature, Cell morphology, Cell orientation, Histological section, Small intestine, Villus

Steeves, A.J., Ho, W., Munisso, M.C., Lomboni, D.J., Larrañaga, E., Omelon, S., Martínez, Elena, Spinello, D., Variola, F., (2020). The implication of spatial statistics in human mesenchymal stem cell response to nanotubular architectures International Journal of Nanomedicine 15, 2151-2169

Introduction: In recent years there has been ample interest in nanoscale modifications of synthetic biomaterials to understand fundamental aspects of cell-surface interactions towards improved biological outcomes. In this study, we aimed at closing in on the effects of nanotubular TiO2 surfaces with variable nanotopography on the response on human mesenchymal stem cells (hMSCs). Although the influence of TiO2 nanotubes on the cellular response, and in particular on hMSC activity, has already been addressed in the past, previous studies overlooked critical morphological, structural and physical aspects that go beyond the simple nanotube diameter, such as spatial statistics. Methods: To bridge this gap, we implemented an extensive characterization of nanotubular surfaces generated by anodization of titanium with a focus on spatial structural variables including eccentricity, nearest neighbour distance (NND) and Voronoi entropy, and associated them to the hMSC response. In addition, we assessed the biological potential of a two-tiered honeycomb nanoarchitecture, which allowed the detection of combinatory effects that this hierarchical structure has on stem cells with respect to conventional nanotubular designs. We have combined experimental techniques, ranging from Scanning Electron (SEM) and Atomic Force (AFM) microscopy to Raman spectroscopy, with computational simulations to characterize and model nanotubular surfaces. We evaluated the cell response at 6 hrs, 1 and 2 days by fluorescence microscopy, as well as bone mineral deposition by Raman spectroscopy, demonstrating substrate-induced differential biological cueing at both the short- and long-term. Results: Our work demonstrates that the nanotube diameter is not sufficient to comprehensively characterize nanotubular surfaces and equally important parameters, such as eccentricity and wall thickness, ought to be included since they all contribute to the overall spatial disorder which, in turn, dictates the overall bioactive potential. We have also demonstrated that nanotubular surfaces affect the quality of bone mineral deposited by differentiated stem cells. Lastly, we closed in on the integrated effects exerted by the superimposition of two dissimilar nanotubular arrays in the honeycomb architecture. Discussion: This work delineates a novel approach for the characterization of TiO2 nanotubes which supports the incorporation of critical spatial structural aspects that have been overlooked in previous research. This is a crucial aspect to interpret cellular behaviour on nanotubular substrates. Consequently, we anticipate that this strategy will contribute to the unification of studies focused on the use of such powerful nanostructured surfaces not only for biomedical applications but also in other technology fields, such as catalysis.

Keywords: Nanotubes, Nanotopography, Spatial statistics, Stem cells, Bone quality

Altay, Gizem, Batlle, Eduard, Fernández-Majada, Vanesa, Martínez, Elena, (2020). In vitro self-organized mouse small intestinal epithelial monolayer protocol Bio-protocol 10, (3), e3514

Developing protocols to obtain intestinal epithelial monolayers that recapitulate in vivo physiology to overcome the limitations of the organoids’ closed geometry has become of great interest during the last few years. Most of the developed culture models showed physiological-relevant cell composition but did not prove self-renewing capacities. Here, we show a simple method to obtain mouse small intestine-derived epithelial monolayers organized into proliferative crypt-like domains, containing stem cells, and differentiated villus-like regions, closely resembling the in vivo cell composition and distribution. In addition, we adapted our model to a tissue culture format compatible with functional studies and prove close to physiological barrier properties of our in vitro epithelial monolayers. Thus, we have set-up a protocol to generate physiologically relevant intestinal epithelial monolayers to be employed in assays where independent access to both luminal and basolateral compartments is needed, such as drug absorption, intracellular trafficking and microbiome-epithelium interaction assays.

Keywords: Mouse intestinal organoids, Adult intestinal stem cells, Matrigel, Intestinal epithelial monolayer, In vitro intestinal epithelial model, Tissue-like functionality, TEER

Monteil, Vanessa, Kwon, Hyesoo, Prado, Patricia, Hagelkrüys, Astrid, Wimmer, Reiner A., Stahl, Martin, Leopoldi, Alexandra, Garreta, Elena, Hurtado Del Pozo, Carmen, Prosper, Felipe, Romero, Juan Pablo, Wirnsberger, Gerald, Zhang, Haibo, Slutsky, Arthur S., Conder, Ryan, Montserrat, Nuria, Mirazimi, Ali, Penninger, Josef M., (2020). Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2 Cell Epub ahead of print,

We have previously provided the first genetic evidence that angiotensin converting enzyme 2 (ACE2) is the critical receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), and ACE2 protects the lung from injury, providing a molecular explanation for the severe lung failure and death due to SARS-CoV infections. ACE2 has now also been identified as a key receptor for SARS-CoV-2 infections, and it has been proposed that inhibiting this interaction might be used in treating patients with COVID-19. However, it is not known whether human recombinant soluble ACE2 (hrsACE2) blocks growth of SARS-CoV-2. Here, we show that clinical grade hrsACE2 reduced SARS-CoV-2 recovery from Vero cells by a factor of 1,000-5,000. An equivalent mouse rsACE2 had no effect. We also show that SARS-CoV-2 can directly infect engineered human blood vessel organoids and human kidney organoids, which can be inhibited by hrsACE2. These data demonstrate that hrsACE2 can significantly block early stages of SARS-CoV-2 infections.

Keywords: COVID-19, Angiotensin converting enzyme 2, Blood vessels, Human organoids, Kidney, Severe acute respiratory syndrome coronavirus, Spike glycoproteins, Treatment

Khurana, K., Guillem-Marti, J., Soldera, F., Mücklich, F., Canal, C., Ginebra, M. P., (2020). Injectable calcium phosphate foams for the delivery of Pitavastatin as osteogenic and angiogenic agent Journal of Biomedical Materials Research - Part B Applied Biomaterials Early View

Apatitic bone cements have been used as a clinical bone substitutes and drug delivery vehicles for therapeutic agents in orthopedic applications. This has led to their combination with different drugs with known ability to foster bone formation. Recent studies have evaluated Simvastatin for its role in enhanced bone regeneration, but its lipophilicity hampers incorporation and release to and from the bone graft. In this study, injectable calcium phosphate foams (i-CPF) based on α-tricalcium phosphate were loaded for the first time with Pitavastatin. The stability of the drug in different conditions relevant to this study, the effect of the drug on the i-CPFs properties, the release profile, and the in vitro biological performance with regard to mineralization and vascularization were investigated. Pitavastatin did not cause any changes in neither the micro nor the macro structure of the i-CPFs, which retained their biomimetic features. PITA-loaded i-CPFs showed a dose-dependent drug release, with early stage release kinetics clearly affected by the evolving microstructure due to the setting of cement. in vitro studies showed dose-dependent enhancement of mineralization and vascularization. Our findings contribute towards the design of controlled release with low drug dosing bone grafts: i-CPFs loaded with PITA as osteogenic and angiogenic agent.

Keywords: Controlled drug release, Endothelial progenitor cells, Mineralization, Rat mesenchymal stem cells, Vascularization

Comelles, Jordi, Fernández-Majada, Vanesa, Berlanga-Navarro, Nuria, Acevedo, Verónica, Paszkowska, Karolina, Martínez, Elena, (2020). Microfabrication of poly(acrylamide) hydrogels with independently controlled topography and stiffness Biofabrication Accepted Manuscript

The stiffness and topography of a cell's extracellular matrix are physical cues that play a key role in regulating processes that determine cellular fate and function. While substrate stiffness can dictate cell differentiation lineage, migration, and self-organization, topographical features can change the cell's differentiation profile or migration ability. Although both physical cues are present and intrinsic to the native tissues in vivo, in vitro studies have been hampered by the lack of technological set-ups that would be compatible with cell culture and characterization. In vitro studies therefore either focused on screening stiffness effects in cells cultured on flat substrates or on determining topography effects in cells cultured onto hard materials. Here, we present a reliable, microfabrication method to obtain well defined topographical structures of micrometer size (5-10 µm) on soft polyacrylamide hydrogels with tunable mechanical stiffness (3-145 kPa) that closely mimic the in vivo situation. Topographically microstructured polyacrylamide hydrogels are polymerized by capillary force lithography using flexible materials as molds. The topographical microstructures are resistant to swelling, can be conformally functionalized by extracellular matrix proteins and sustain the growth of cell lines (fibroblasts and myoblasts) and primary cells (mouse intestinal epithelial cells). Our method can independently control stiffness and topography, which allows to individually assess the contribution of each physical cue to cell response or to explore potential synergistic effects. We anticipate that our fabrication method will be of great utility in tissue engineering and biophysics, especially for applications where the use of complex in vivo-like environments is of paramount importance.

De Matteis, Valeria, Rizzello, Loris, (2020). Noble metals and soft bio-inspired nanoparticles in retinal diseases treatment: A perspective Cells 9, (3), 679

We are witnessing an exponential increase in the use of different nanomaterials in a plethora of biomedical fields. We are all aware of how nanoparticles (NPs) have influenced and revolutionized the way we supply drugs or how to use them as therapeutic agents thanks to their tunable physico-chemical properties. However, there is still a niche of applications where NP have not yet been widely explored. This is the field of ocular delivery and NP-based therapy, which characterizes the topic of the current review. In particular, many efforts are being made to develop nanosystems capable of reaching deeper sections of the eye such as the retina. Particular attention will be given here to noble metal (gold and silver), and to polymeric nanoparticles, systems consisting of lipid bilayers such as liposomes or vesicles based on nonionic surfactant. We will report here the most relevant literature on the use of different types of NPs for an efficient delivery of drugs and bio-macromolecules to the eyes or as active therapeutic tools.

Keywords: Bio-inspired NPs, Drug delivery, Noble metals NPs, Retinal diseases

Rustler, Karin, Gomila, Alexandre, Maleeva, Galyna, Gorostiza, Pau, Bregestovski, Piotr, König, Burkhard, (2020). Optical Control of GABAA Receptors with a Fulgimide-Based Potentiator Chemistry - A European Journal Accepted Articles,

Optogenetic and photopharmacological tools to manipulate neuronal inhibition have limited efficacy and reversibility. We report the design, synthesis, and biological evaluation of Fulgazepam, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ-aminobutyric acid receptors (GABA A Rs) and displays full and reversible photoswitching in vitro and in vivo. The compound enables high-resolution studies of GABAergic neurotransmission, and phototherapies based on localized, acute, and reversible neuroinhibition.

Palacio, F., Fonollosa, J., burgués, J., Gomez, J. M., Marco, S., (2020). Pulsed-temperature metal oxide gas sensors for microwatt power consumption IEEE Access 8, 70938-70946

Metal Oxide (MOX) gas sensors rely on chemical reactions that occur efficiently at high temperatures, resulting in too-demanding power requirements for certain applications. Operating the sensor under a Pulsed-Temperature Operation (PTO), by which the sensor heater is switched ON and OFF periodically, is a common practice to reduce the power consumption. However, the sensor performance is degraded as the OFF periods become larger. Other research works studied, generally, PTO schemes applying waveforms to the heater with time periods of seconds and duty cycles above 20%. Here, instead, we explore the behaviour of PTO sensors working under aggressive schemes, reaching power savings of 99% and beyond with respect to continuous heater stimulation. Using sensor sensitivity and the limit of detection, we evaluated four Ultra Low Power (ULP) sensors under different PTO schemes exposed to ammonia, ethylene, and acetaldehyde. Results show that it is possible to operate the sensors with total power consumption in the range of microwatts. Despite the aggressive power reduction, sensor sensitivity suffers only a moderate decline and the limit of detection may degrade up to a factor five. This is, however, gas-dependent and should be explored on a case-by-case basis since, for example, the same degradation has not been observed for ammonia. Finally, the run-in time, i.e., the time required to get a stable response immediately after switching on the sensor, increases when reducing the power consumption, from 10 minutes to values in the range of 10–20 hours for power consumptions smaller than 200 microwatts.

Keywords: Robot sensing systems, Temperature sensors, Heating systems, Gas detectors, Power demand, Sensitivity, Electronic nose, gas sensors, low-power operation, machine olfaction, pulsed-temperature operation, temperature modulation

Ferrer, I., Zelaya, M. V., Aguiló García, M., Carmona, M., López-González, I., Andrés-Benito, P., Lidón, L., Gavín, R., Garcia-Esparcia, P., del Rio, J. A., (2020). Relevance of host tau in tau seeding and spreading in tauopathies Brain Pathology 30, (2), 298-318

Human tau seeding and spreading occur following intracerebral inoculation of brain homogenates obtained from tauopathies in transgenic mice expressing natural or mutant tau, and in wild-type (WT) mice. The present study was geared to learning about the patterns of tau seeding, the cells involved and the characteristics of tau following intracerebral inoculation of homogenates from primary age-related tauopathy (PART: neuronal 4Rtau and 3Rtau), aging-related tau astrogliopathy (ARTAG: astrocytic 4Rtau) and globular glial tauopathy (GGT: 4Rtau with neuronal deposits and specific tau inclusions in astrocytes and oligodendrocytes). For this purpose, young and adult WT mice were inoculated unilaterally in the hippocampus or in the lateral corpus callosum with sarkosyl-insoluble fractions from PART, ARTAG and GGT cases, and were killed at variable periods of three to seven months. Brains were processed for immunohistochemistry in paraffin sections. Tau seeding occurred in the ipsilateral hippocampus and corpus callosum and spread to the septal nuclei, periventricular hypothalamus and contralateral corpus callosum, respectively. Tau deposits were mainly found in neurons, oligodendrocytes and threads; the deposits were diffuse or granular, composed of phosphorylated tau, tau with abnormal conformation and 3Rtau and 4Rtau independently of the type of tauopathy. Truncated tau at the aspartic acid 421 and ubiquitination were absent. Tau deposits had the characteristics of pre-tangles. A percentage of intracellular tau deposits co-localized with active (phosphorylated) tau kinases p38 and ERK 1/2. Present study shows that seeding and spreading of human tau into the brain of WT mice involves neurons and glial cells, mainly oligodendrocytes, thereby supporting the idea of a primary role of oligodendrogliopathy, together with neuronopathy, in the progression of tauopathies. In addition, it suggests that human tau inoculation modifies murine tau metabolism with the production and deposition of 3Rtau and 4Rtau, and by activation of specific tau kinases in affected cells.

Keywords: Aging-related tau astrogliopathy, Globular glial tauopathy, Primary age-related tauopathy, Seeding, Spreading, Tau, Tauopathies

Rodríguez-Pereira, Cristina, Lagunas, Anna, Casanellas, Ignasi, Vida, Yolanda, Pérez-Inestrosa, Ezequiel, Andrades, José A., Becerra, José, Samitier, Josep, Blanco, Francisco J., Magalhães, Joana, (2020). RGD-dendrimer-poly(L-lactic) acid nanopatterned substrates for the early chondrogenesis of human mesenchymal stromal cells derived from osteoarthritic and healthy donors Materials 13, (10), 2247

Aiming to address a stable chondrogenesis derived from mesenchymal stromal cells (MSCs) to be applied in cartilage repair strategies at the onset of osteoarthritis (OA), we analyzed the effect of arginine–glycine–aspartate (RGD) density on cell condensation that occurs during the initial phase of chondrogenesis. For this, we seeded MSC-derived from OA and healthy (H) donors in RGD-dendrimer-poly(L-lactic) acid (PLLA) nanopatterned substrates (RGD concentrations of 4 × 10−9, 10−8, 2.5 × 10−8, and 10−2 w/w), during three days and compared to a cell pellet conventional three-dimensional culture system. Molecular gene expression (collagens type-I and II–COL1A1 and COL2A1, tenascin-TNC, sex determining region Y-box9-SOX9, and gap junction protein alpha 1–GJA1) was determined as well as the cell aggregates and pellet size, collagen type-II and connexin 43 proteins synthesis. This study showed that RGD-tailored first generation dendrimer (RGD-Cys-D1) PLLA nanopatterned substrates supported the formation of pre-chondrogenic condensates from OA- and H-derived human bone marrow-MSCs with enhanced chondrogenesis regarding the cell pellet conventional system (presence of collagen type-II and connexin 43, both at the gene and protein level). A RGD-density dependent trend was observed for aggregates size, in concordance with previous studies. Moreover, the nanopatterns’ had a higher effect on OA-derived MSC morphology, leading to the formation of bigger and more compact aggregates with improved expression of early chondrogenic markers.

Keywords: Cell condensation, Gap junctions, RGD-density, Chondrogenic differentiation, Osteoarthritis

Xu, D., Wang, Y., Liang, C., You, Y., Sanchez, S., Ma, X., (2020). Self-propelled micro/nanomotors for on-demand biomedical cargo transportation Small Early View

Micro/nanomotors (MNMs) are miniaturized machines that can perform assigned tasks at the micro/nanoscale. Over the past decade, significant progress has been made in the design, preparation, and applications of MNMs that are powered by converting different sources of energy into mechanical force, to realize active movement and fulfill on-demand tasks. MNMs can be navigated to desired locations with precise controllability based on different guidance mechanisms. A considerable research effort has gone into demonstrating that MNMs possess the potential of biomedical cargo loading, transportation, and targeted release to achieve therapeutic functions. Herein, the recent advances of self-propelled MNMs for on-demand biomedical cargo transportation, including their self-propulsion mechanisms, guidance strategies, as well as proof-of-concept studies for biological applications are presented. In addition, some of the major challenges and possible opportunities of MNMs are identified for future biomedical applications in the hope that it may inspire future research.

Keywords: Biomedical applications, Cargo transportation, Guidance strategies, Micro/nanomotors, Self-propulsion

De Corato, Marco, Arqué, Xavier, Patiño, Tania, Arroyo, Marino, Sánchez, Samuel, Pagonabarraga, Ignacio, (2020). Self-propulsion of active colloids via ion release: Theory and experiments Physical Review Letters 124, (10), 108001

We study the self-propulsion of a charged colloidal particle that releases ionic species using theory and experiments. We relax the assumptions of thin Debye length and weak nonequilibrium effects assumed in classical phoretic models. This leads to a number of unexpected features that cannot be rationalized considering the classic phoretic framework: an active particle can reverse the direction of motion by increasing the rate of ion release and can propel even with zero surface charge. Our theory predicts that there are optimal conditions for self-propulsion and a novel regime in which the velocity is insensitive to the background electrolyte concentration. The theoretical results quantitatively capture the salt-dependent velocity measured in our experiments using active colloids that propel by decomposing urea via a surface enzymatic reaction.

Torner, M., Mangal, A., Scharnagl, H., Jansen, C., Praktiknjo, M., Queck, A., Gu, W., Schierwagen, R., Lehmann, J., Uschner, F. E., Graf, C., Strassburg, C. P., Fernandez, J., Stojakovic, T., Woitas, R., Trebicka, J., (2020). Sex specificity of kidney markers to assess prognosis in cirrhotic patients with TIPS Liver International 40, (1), 186-193

Background & Aims: Renal function assessed by creatinine is a key prognostic factor in cirrhotic patients. However, creatinine is influenced by several factors, rendering interpretation difficult in some situations. This is especially important in early stages of renal dysfunction where renal impairment might not be accompanied by an increase in creatinine. Other parameters, such as cystatin C (CysC) and beta‐trace protein (BTP), have been evaluated to fill this gap. However, none of these studies have considered the role of the patient's sex. The present study analysed CysC and BTP to evaluate their prognostic value and differentiate them according to sex. Patients and methods: CysC and BTP were measured in 173 transjugular intrahepatic portosystemic shunt (TIPS)-patients from the NEPTUN-STUDY(NCT03628807) and analysed their relationship with mortality and sex. Propensity score for age, MELD, etiology and TIPS indication was used. Results: Cystatin C and BTP showed excellent correlations with creatinine values at baseline and follow-up. CysC was an independent predictor of overall mortality (HR = 1.66(1.33-2.06)) with an AUC of 0.75 and identified a cut-off of 1.55 mg/L in the whole cohort. Interestingly, CysC was significantly lower in females, also after propensity score matching. In males, the only independent predictor was the creatinine level (HR = 1.54(1.25-1.58)), while in females CysC levels independently predicted mortality (HR = 3.17(1.34-7.52)). Conclusion: This study demonstrates for the first time that in TIPS-patients creatinine predicts mortality in males better than in females, whereas CysC is a better predictor of mortality in females. These results may influence future clinical decisions on therapeutic options for example, allocation for liver transplantation in TIPS-patients.

Keywords: Beta-trace protein, Cirrhosis, Cystatin C, Portal hypertension, Renal function

Puigbò, J. Y., Arsiwalla, X. D., González-Ballester, M. A., Verschure, P., (2020). Switching operation modes in the neocortex via cholinergic neuromodulation Molecular Neurobiology 57, (1), 139-149

In order to deal with the uncertainty in the world, our brains need to be able to flexibly switch between the exploration of new sensory representations and exploitation of previously acquired ones. This requires forming accurate estimations of what and how much something is expected. While modeling has allowed for the development of several ways to form predictions, how the brain could implement those is still under debate. Here, we recognize acetylcholine as one of the main neuromodulators driving learning based on uncertainty, promoting the exploration of new sensory representations. We identify its interactions with cortical inhibitory interneurons and derive a biophysically grounded computational model able to capture and learn from uncertainty. This model allows us to understand inhibition beyond gain control by suggesting that different interneuron subtypes either encode predictions or estimate their uncertainty, facilitating detection of unexpected cues. Moreover, we show how acetylcholine-like neuromodulation uniquely interacts with global and local sources of inhibition, disrupting perceptual certainty and promoting the rapid acquisition of new perceptual cues. Altogether, our model proposes that cortical acetylcholine favors sensory exploration over exploitation in a cortical microcircuit dedicated to estimating sensory uncertainty.

Monferrer, Ezequiel, Martínn-Vañó, Susana, Carretero, Aitor, Garcíaa-Lizarribar, Andrea, Burgos-Panadero, Rebeca, Navarro, Samuel, Samitier, Josep, Noguera, Rosa, (2020). A three-dimensional bioprinted model to evaluate the effect of stiffness on neuroblastoma cell cluster dynamics and behavior Scientific Reports 10, (1), 6370

Three-dimensional (3D) bioprinted culture systems allow to accurately control microenvironment components and analyze their effects at cellular and tissue levels. The main objective of this study was to identify, quantify and localize the effects of physical-chemical communication signals between tumor cells and the surrounding biomaterial stiffness over time, defining how aggressiveness increases in SK-N-BE(2) neuroblastoma (NB) cell line. Biomimetic hydrogels with SK-N-BE(2) cells, methacrylated gelatin and increasing concentrations of methacrylated alginate (AlgMA 0%, 1% and 2%) were used. Young’s modulus was used to define the stiffness of bioprinted hydrogels and NB tumors. Stained sections of paraffin-embedded hydrogels were digitally quantified. Human NB and 1% AlgMA hydrogels presented similar Young´s modulus mean, and orthotopic NB mice tumors were equally similar to 0% and 1% AlgMA hydrogels. Porosity increased over time; cell cluster density decreased over time and with stiffness, and cell cluster occupancy generally increased with time and decreased with stiffness. In addition, cell proliferation, mRNA metabolism and antiapoptotic activity advanced over time and with stiffness. Together, this rheological, optical and digital data show the potential of the 3D in vitro cell model described herein to infer how intercellular space stiffness patterns drive the clinical behavior associated with NB patients.

Keywords: Biomaterials - cells, Paediatric cancer

Velasco, Ferran, Fernandez-Costa, Juan M., Neves, Luisa, Ramon Azcon, Javier, (2020). Volumetric CNT-doped Gelatin-Cellulose scaffold for skeletal muscle tissue engineering Nanoscale Advances ahead,

Currently, the fabrication of scaffolds for engineered skeletal muscle tissue is unable to reach the millimeter size. The main drawbacks are the poor nutrients diffusion, lack of internal structure to align precursor cells as well as poor mechanical and electric properties. Herein, we present a combination of gelatin-carboxymethyl cellulose materials polymerised by a cryogelation process that allowed us to reach scaffold fabrication up to millimeters size and solve the main problems related with large size muscle tissue constructs. 1) By incorporating carbon nanotubes (CNT) we can improve the electrical properties of the scaffold, thereby enhancing tissue maturation when applying an electric pulse stimulus (EPS). 2) We have fabricated an anisotropic internal three-dimensional microarchitecture pore distribution with high aligned morphology to enhance cells alignment, cell fusion and myotubes formation. With this set up, we were able to generate a fully functional skeletal muscle tissue using a combination of EPS and our doped-biocomposite scaffold and obtain a mature tissue in a millimeter scale. We also characterized pore distribution, swelling, stiffness and conductivity of the scaffold. Moreover, we proved that the cells are viable and able to fuse in a three-dimensional (3D) functional myotubes throughout the scaffold. In conclusion, we fabricate a biocompatible and customizable scaffold for 3D cell culture suitable for a wide range of application such as organ-on-a-chip, drug screening, transplantation and disease modelling.

Blancas, Maria, Valero, Cristina, Mura, Anna, Vouloutsi, Vasiliki, Verschure, P., (2020). "CREA": An inquiry-based methodology to teach robotics to children Robotics in Education International Conference on Robotics in Education (RiE) , Springer International Publishing (Vienna, Austria) Advances in Intelligent Systems and Computing (AISC, volume 1023), 45-51

Learning programming and robotics offers the opportunity to practice problem-solving, creativity, and team-work and it provides important competencies to train for the 21st century. However, programming can be challenging, and children may encounter difficulties in learning the syntax or using the coding environment. To address this issue, we have developed a methodology for teaching programming, design and robotics based on inquiry-based learning and hands-on oriented activities together with visual programming. We have applied and evaluated this new methodology within the extracurricular activity of an international elementary school in Barcelona. Our findings showed acquisition and learning of technical language, understanding of electronics devices, understanding the mapping of coding into action via the robot’s behavior. This suggests that our approach is a valid and effective teaching methodology for the instructional design of robotics and programming.

Keywords: Educational technology, Instructional design, Robotics

Wang, S., Hu, Y., Burgués, J., Marco, S., Liu, S.-L., (2020). Prediction of gas concentration using gated recurrent neural networks 2nd IEEE International Conference on Artificial Intelligence Circuits and Systems (AICAS) , IEEE (Genova, Italy) , 178-182

Low-cost gas sensors allow for large-scale spatial monitoring of air quality in the environment. However they require calibration before deployment. Methods such as multivariate regression techniques have been applied towards sensor calibration. In this work, we propose instead, the use of deep learning methods, particularly, recurrent neural networks for predicting the gas concentrations based on the outputs of these sensors. This paper presents a first study of using Gated Recurrent Unit (GRU) neural network models for gas concentration prediction. The GRU networks achieve on average, a 44.69% and a 25.17% RMSE improvement in concentration prediction on a gas dataset when compared with Support Vector Regression (SVR) and Multilayer Perceptron (MLP) models respectively. With the current advances in deep network hardware accelerators, these networks can be combined with the sensors for a compact embedded system suitable for edge applications.

Keywords: Robot sensing systems, Predictive models, Logic gates, Gas detectors, Training, Temperature measurement, Support vector machines