Biomimetic systems for cell engineering


The Biomimetic systems for cell engineering group is a junior group under IBEC’s Tenure Track scheme.

About

In vitro assay platforms involving human cells are increasingly important to study tissue development, tissue regeneration, construct models of disease or develop systems for therapeutic screening that predict the human in vivo context.

The main conceptual problem of the standard in vitro cell-based assays is that they rely on two dimensional monolayer cellular cultures, which fail to replicate the complexity of living systems. There is an urgent need to create technological platforms with complex cell culture systems that mimic better the tissue-like cellular microenvironment.

The caption is: Mimicking small intestinal tissue by culturing intestinal-organoid derived cells on poly(ethylene glycol) diacrylate (PEGDA) microstructures. Cell nuclei are stained in green and actin cytoskeleton in red.

We propose to combine engineering microfabrication technologies, tissue engineering concepts and recent advances in stem cell research, exploiting stem cell unique properties, to create cell culture microenvironments that will go beyond current 3D in vitro models. Resulting in vitro tissue equivalents aim at recapitulating in vivo cell functionality, cell renewal and migration, multicell-type differentiation and cell-matrix and cell-cell interactions. The cell culture platforms proposed will provide physiologically relevant and highly reproducible data, and they will be compatible with conventional cell culture assays and high-throughput testing. The new organotypic cell culture platforms will aim to advance the in vitro modelling of diseases, the preclinical screening for drug toxicity, the understanding of organ development and the regenerative medicine applications. Current main projects are: (i) to engineer and validate a complex in vitro model of small intestinal epithelium and (ii) to engineer and validate a novel in vitro model of engineered cardiac tissue.

Staff

 

Elena Martínez Fraiz | Group Leader
Jordi Comelles Pujadas | Senior Researcher
Vanesa Fernández Majada | Senior Researcher
Livia Neves Borgheti Cardoso | Postdoctoral Researcher
Renata Kelly Da Palma | Postdoctoral Researcher
María García Díaz | Postdoctoral Researcher
Núria Torras Andrés | Postdoctoral Researcher
Aina Abad Lázaro | PhD Student
Angela Cirulli | PhD Student
Verónica Cecilia Acevedo Morejón | Laboratory Technician
Daniel Vera Ibañez | Visiting Researcher

 

 


Projects

EU-funded projects
COMIET Engineering Complex Intestinal Epithelial Tissue Models (2015-2020) ERC Consolidator Grant Elena Martínez
BRIGHTER BIOPRINTING BY LIGHT-SHEET LITHOGRAPHY (2019-2022) European Commission FET Open Elena Martínez
National projects
INDUCT Dispositivo de multitejido intestinal para la monitorización de la comunicación entre epitelio y músculo en condiciones patológicas (2018-2021) MINECO Elena Martínez
ENGUT Engineered models of intestinal epithelial tissue: assessing in vivo-like functional properties (2019-2020) Bist Ignite Program Elena Martínez
Finished projects
COMIET Engineering Complex Intestinal Epithelial Tissue Models (2015-2020) ERC Consolidator Grant Elena Martínez
GLAM Glass-Laser Multiplexed Biosensor (2015-2019) European Commission (H2020) – PHC-10-2015 Elena Martínez
MINAHE5 (Bio)funcionalización de Micro- y NanoHerramientas en Suspensión para Aplicaciones en Células Vivas (2015-2017) MINECO Maria Lluïsa Pérez

Publications

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 12, 025008

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


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.


Cutrale, Francesco, Rodriguez, Daniel, Hortigüela, Verónica, Chiu, Chi-Li, Otterstrom, Jason, Mieruszynski, Stephen, Seriola, Anna, Larrañaga, Enara, Raya, Angel, Lakadamyali, Melike, Fraser, Scott E., Martinez, Elena, Ojosnegros, Samuel, (2019). Using enhanced number and brightness to measure protein oligomerization dynamics in live cells Nature Protocols 14, 616-638

Protein dimerization and oligomerization are essential to most cellular functions, yet measurement of the size of these oligomers in live cells, especially when their size changes over time and space, remains a challenge. A commonly used approach for studying protein aggregates in cells is number and brightness (N&B), a fluorescence microscopy method that is capable of measuring the apparent average number of molecules and their oligomerization (brightness) in each pixel from a series of fluorescence microscopy images. We have recently expanded this approach in order to allow resampling of the raw data to resolve the statistical weighting of coexisting species within each pixel. This feature makes enhanced N&B (eN&B) optimal for capturing the temporal aspects of protein oligomerization when a distribution of oligomers shifts toward a larger central size over time. In this protocol, we demonstrate the application of eN&B by quantifying receptor clustering dynamics using electron-multiplying charge-coupled device (EMCCD)-based total internal reflection microscopy (TIRF) imaging. TIRF provides a superior signal-to-noise ratio, but we also provide guidelines for implementing eN&B in confocal microscopes. For each time point, eN&B requires the acquisition of 200 frames, and it takes a few seconds up to 2 min to complete a single time point. We provide an eN&B (and standard N&B) MATLAB software package amenable to any standard confocal or TIRF microscope. The software requires a high-RAM computer (64 Gb) to run and includes a photobleaching detrending algorithm, which allows extension of the live imaging for more than an hour.


Castaño, Albert G., García-Díaz, María, Torras, Núria, Altay, Gizem, Comelles, Jordi, Martínez, Elena, (2019). Dynamic photopolymerization produces complex microstructures on hydrogels in a moldless approach to generate a 3D intestinal tissue model Biofabrication 11, (2), 025007

Epithelial tissues contain three-dimensional (3D) complex microtopographies that are essential for proper performance. These microstructures provide cells with the physicochemical cues needed to guide their self-organization into functional tissue structures. However, most in vitro models do not implement these 3D architectural features. The main problem is the availability of simple fabrication techniques that can reproduce the complex geometries found in native tissues on the soft polymeric materials required as cell culture substrates. In this study reaction-diffusion mediated photolithography is used to fabricate 3D microstructures with complex geometries on poly(ethylene glycol)-based hydrogels in a single step and moldless approach. By controlling fabrication parameters such as the oxygen diffusion/depletion timescales, the distance to the light source and the exposure dose, the dimensions and geometry of the microstructures can be well-defined. In addition, copolymerization of poly(ethylene glycol) with acrylic acid improves control of the dynamic reaction-diffusion processes that govern the free-radical polymerization of highly-diluted polymeric solutions. Moreover, acrylic acid allows adjusting the density of cell adhesive ligands while preserving the mechanical properties of the hydrogels. The method proposed is a simple, single-step, and cost-effective strategy for producing models of intestinal epithelium that can be easily integrated into standard cell culture platforms.


Martinez, Elena, St-Pierre, Jean-Philippe, Variola, Fabio, (2019). Advanced bioengineering technologies for preclinical research Advances in Physics: X 4, (1), 1622451

Current in vitro practices must overcome important challenges to compare favorably with human studies. The limited applicability of conventional in vitro assays and strategies can be explained by the fact that standard approaches do not enable recapitulation of the complexity of human tissues and physiological functions. To address this challenge, novel bioengineering tools, techniques and technologies are rapidly emerging to advance current fundamental knowledge and innovate in vitro practices. For example, organs-on-a-chip have recently appeared as a small-scale solution to overcome the transability, financial and ethical concerns associated with animal studies in drug discovery and development. In parallel, biomimetic interfaces are increasingly recapitulating 3D structures with tissue-like dynamic properties to allow in-depth investigation of disease mechanisms. This review aims at highlighting current bioengineering approaches poised to address the shortcomings of conventional in vitro research practices towards the generation of more effective solutions for improving human health.


Valls-Margarit, M., Iglesias-García, O., Di Guglielmo, C., Sarlabous, L., Tadevosyan, K., Paoli, R., Comelles, J., Blanco-Almazán, D., Jiménez-Delgado, S., Castillo-Fernández, O., Samitier, J., Jané, R., Martínez, Elena, Raya, Á., (2019). Engineered macroscale cardiac constructs elicit human myocardial tissue-like functionality Stem Cell Reports 13, (1), 207-220

In vitro surrogate models of human cardiac tissue hold great promise in disease modeling, cardiotoxicity testing, and future applications in regenerative medicine. However, the generation of engineered human cardiac constructs with tissue-like functionality is currently thwarted by difficulties in achieving efficient maturation at the cellular and/or tissular level. Here, we report on the design and implementation of a platform for the production of engineered cardiac macrotissues from human pluripotent stem cells (PSCs), which we term “CardioSlice.” PSC-derived cardiomyocytes, together with human fibroblasts, are seeded into large 3D porous scaffolds and cultured using a parallelized perfusion bioreactor with custom-made culture chambers. Continuous electrical stimulation for 2 weeks promotes cardiomyocyte alignment and synchronization, and the emergence of cardiac tissue-like properties. These include electrocardiogram-like signals that can be readily measured on the surface of CardioSlice constructs, and a response to proarrhythmic drugs that is predictive of their effect in human patients.

Keywords: Cardiac tissue engineering, CardioSlice, ECG-like signals, Electrical stimulation, Heart physiology, Human induced pluripotent stem cells, Perfusion bioreactor, Tissue-like properties


Hortigüela, Verónica, Larrañaga, Enara, Lagunas, Anna, Acosta, Gerardo A., Albericio, Fernando, Andilla, Jordi, Loza-Alvarez, Pablo, Martínez, Elena, (2019). Large-area biomolecule nanopatterns on diblock copolymer surfaces for cell adhesion studies Nanomaterials 9, (4), 579

Cell membrane receptors bind to extracellular ligands, triggering intracellular signal transduction pathways that result in specific cell function. Some receptors require to be associated forming clusters for effective signaling. Increasing evidences suggest that receptor clustering is subjected to spatially controlled ligand distribution at the nanoscale. Herein we present a method to produce in an easy, straightforward process, nanopatterns of biomolecular ligands to study ligand–receptor processes involving multivalent interactions. We based our platform in self-assembled diblock copolymers composed of poly(styrene) (PS) and poly(methyl methacrylate) (PMMA) that form PMMA nanodomains in a closed-packed hexagonal arrangement. Upon PMMA selective functionalization, biomolecular nanopatterns over large areas are produced. Nanopattern size and spacing can be controlled by the composition of the block-copolymer selected. Nanopatterns of cell adhesive peptides of different size and spacing were produced, and their impact in integrin receptor clustering and the formation of cell focal adhesions was studied. Cells on ligand nanopatterns showed an increased number of focal contacts, which were, in turn, more matured than those found in cells cultured on randomly presenting ligands. These findings suggest that our methodology is a suitable, versatile tool to study and control receptor clustering signaling and downstream cell behavior through a surface-based ligand patterning technique.


Altay, Gizem, Larrañaga, Enara, Tosi, Sébastien, Barriga, Francisco M., Batlle, Eduard, Fernández-Majada, Vanesa, Martínez, Elena, (2019). Self-organized intestinal epithelial monolayers in crypt and villus-like domains show effective barrier function Scientific Reports 9, (1), 10140

Intestinal organoids have emerged as a powerful in vitro tool for studying intestinal biology due to their resemblance to in vivo tissue at the structural and functional levels. However, their sphere-like geometry prevents access to the apical side of the epithelium, making them unsuitable for standard functional assays designed for flat cell monolayers. Here, we describe a simple method for the formation of epithelial monolayers that recapitulates the in vivo-like cell type composition and organization and that is suitable for functional tissue barrier assays. In our approach, epithelial monolayer spreading is driven by the substrate stiffness, while tissue barrier function is achieved by the basolateral delivery of medium enriched with stem cell niche and myofibroblast-derived factors. These monolayers contain major intestinal epithelial cell types organized into proliferating crypt-like domains and differentiated villus-like regions, closely resembling the in vivo cell distribution. As a unique characteristic, these epithelial monolayers form functional epithelial barriers with an accessible apical surface and physiologically relevant transepithelial electrical resistance values. Our technology offers an up-to-date and novel culture method for intestinal epithelium, providing an in vivo-like cell composition and distribution in a tissue culture format compatible with high-throughput drug absorption or microbe-epithelium interaction studies.


de Goede, Michiel, Chang, Lantian, Mu, Jinfeng, Dijkstra, Meindert, Obregón, Raquel, Martínez, Elena, Padilla, Laura, Mitjans, Francesc, Garcia-Blanco, Sonia M., (2019). Al2O3:Yb3+ integrated microdisk laser label-free biosensor Optics Letters 44, (24), 5937-5940

Whispering gallery mode resonator lasers hold the promise of an ultralow intrinsic limit of detection. However, the widespread use of these devices for biosensing applications has been hindered by the complexity and lack of robustness of the proposed configurations. In this work, we demonstrate biosensing with an integrated microdisk laser. Al2O3doped with Yb3+ was utilized because of its low optical losses as well as its emission in the range 1020–1050 nm, outside the absorption band of water. Single-mode laser emission was obtained at a wavelength of 1024 nm with a linewidth of 250 kHz while the microdisk cavity was submerged in water. A limit of detection of 300 pM (3.6 ng/ml) of the protein rhS100A4 in urine was experimentally demonstrated, showing the potential of the proposed devices for biosensing.

Keywords: Distributed feedback lasers, Fiber lasers, Laser modes, Microdisk lasers, Single mode lasers, Tunable lasers


de Goede, M., Dijkstra, M., Obregón, R., Ramón-Azcón, J., Martínez, Elena, Padilla, L., Mitjans, F., Garcia-Blanco, S. M., (2019). Al2O3 microring resonators for the detection of a cancer biomarker in undiluted urine Optics Express 27, (13), 18508-18521

Concentrations down to 3 nM of the rhS100A4 protein, associated with human tumor development, have been detected in undiluted urine using an integrated sensor based on microring resonators in the emerging Al2O3 photonic platform. The fabricated microrings were designed for operation in the C-band (λ = 1565 nm) and exhibited a high-quality factor in air of 3.2 × 105. The bulk refractive index sensitivity of the devices was ~100 nm/RIU (for TM polarization) with a limit of detection of ~10−6 RIU. A surface functionalization protocol was developed to allow for the selective binding of the monoclonal antibodies designed to capture the target biomarker to the surface of the Al2O3 microrings. The detection of rhS100A4 proteins at clinically relevant concentrations in urine is a big milestone towards the use of biosensors for the screening and early diagnosis of different cancers. Biosensors based on this microring technology can lead to portable, multiplexed and easy-to-use point of care devices.

Keywords: Distributed feedback lasers, Effective refractive index, Laser coupling, Polarization maintaining fibers, Refractive index, Scanning electron microscopy


García-Díaz, María, Birch, Ditlev, Wan, Feng, Mørck Nielsen, Hanne, (2018). The role of mucus as an invisible cloak to transepithelial drug delivery by nanoparticles Advanced Drug Delivery Reviews 124, 107-124

Mucosal administration of drugs and drug delivery systems has gained increasing interest. However, nanoparticles intended to protect and deliver drugs to epithelial surfaces require transport through the surface-lining mucus. Translation from bench to bedside is particularly challenging for mucosal administration since a variety of parameters will influence the specific barrier properties of the mucus including the luminal fluids, the microbiota, the mucus composition and clearance rate, and the condition of the underlying epithelia. Besides, after administration, nanoparticles interact with the mucosal components, forming a biomolecular corona that modulates their behavior and fate after mucosal administration. These interactions are greatly influenced by the nanoparticle properties, and therefore different designs and surface-engineering strategies have been proposed. Overall, it is essential to evaluate these biomolecule-nanoparticle interactions by complementary techniques using complex and relevant mucus barrier matrices.

Keywords: Nanoparticle formulation strategies, Corona formation, Digestive tract, Respiratory tract, Luminal content, Methodologies, Analysis


Hortigüela, Verónica, Larrañaga, Enara, Cutrale, Francesco, Seriola', Anna, García-Díaz, María, Lagunas, Anna, Andilla, Jordi, Loza-Alvarez, Pablo, Samitier, Josep, Ojosnegros', Samuel, Martinez, Elena, (2018). Nanopatterns of surface-bound ephrinB1 produce multivalent ligand-receptor interactions that tune EphB2 receptor clustering Nano Letters 18, (1), 629-637

Here we present a nanostructured surface able to produce multivalent interactions between surface-bound ephrinB1 ligands and membrane EphB2 receptors. We created ephrinB1 nanopatterns of regular size (<30 nm in diameter) by using self-assembled diblock copolymers. Next, we used a statistically enhanced version of the Number and Brightness technique, which can discriminate - with molecular sensitivity - the oligomeric states of diffusive species to quantitatively track the EphB2 receptor oligomerization process in real time. The results indicate that a stimulation using randomly distributed surface-bound ligands was not sufficient to fully induce receptor aggregation. Conversely, when nanopatterned onto our substrates, the ligands effectively induced a strong receptor oligomerization. This presentation of ligands improved the clustering efficiency of conventional ligand delivery systems, as it required a 9-fold lower ligand surface coverage and included faster receptor clustering kinetics compared to traditional crosslinked ligands. In conclusion, nanostructured diblock copolymers constitute a novel strategy to induce multivalent ligand-receptor interactions leading to a stronger, faster, and more efficient receptor activation, thus providing a useful strategy to precisely tune and potentiate receptor responses. The efficiency of these materials at inducing cell responses can benefit applications such as the design of new bioactive materials and drug-delivery systems.


Macedo, Maria Helena, Araújo, Francisca, Martínez, Elena, Barrias, Cristina, Sarmento, Bruno, (2018). iPSC-Derived enterocyte-like cells for drug absorption and metabolism studies Trends in Molecular Medicine 24, (8), 696-708

Intestinal cell models have been widely studied and used to evaluate absorption and metabolism of drugs in the small intestine, constituting valuable tools as a first approach to evaluate the behavior of new drugs. However, such cell models might not be able to fully predict the absorption mechanisms and metabolic pathways of the tested compounds. In recent years, induced pluripotent stem cells (iPSCs) differentiated into enterocyte-like cells have been proposed as more biorelevant intestinal models. In this review, we describe mechanisms underlying the differentiation of iPSCs into enterocyte-like cells, appraise the usefulness of these cells in tridimensional intestinal models, and discuss their suitability to be used in the future for drug screening.

Keywords: iPSCs, Enterocytes, Differentiation, Small intestine, Drug absorption, Intestinal models


Torras, N., García-Díaz, M., Fernández-Majada, V., Martínez, Elena, (2018). Mimicking epithelial tissues in three-dimensional cell culture models Frontiers in Bioengineering and Biotechnology 6, Article 197

Epithelial tissues are composed of layers of tightly connected cells shaped into complex three-dimensional (3D) structures such as cysts, tubules, or invaginations. These complex 3D structures are important for organ-specific functions and often create biochemical gradients that guide cell positioning and compartmentalization within the organ. One of the main functions of epithelia is to act as physical barriers that protect the underlying tissues from external insults. In vitro, epithelial barriers are usually mimicked by oversimplified models based on cell lines grown as monolayers on flat surfaces. While useful to answer certain questions, these models cannot fully capture the in vivo organ physiology and often yield poor predictions. In order to progress further in basic and translational research, disease modeling, drug discovery, and regenerative medicine, it is essential to advance the development of new in vitro predictive models of epithelial tissues that are capable of representing the in vivo-like structures and organ functionality more accurately. Here, we review current strategies for obtaining biomimetic systems in the form of advanced in vitro models that allow for more reliable and safer preclinical tests. The current state of the art and potential applications of self-organized cell-based systems, organ-on-a-chip devices that incorporate sensors and monitoring capabilities, as well as microfabrication techniques including bioprinting and photolithography, are discussed. These techniques could be combined to help provide highly predictive drug tests for patient-specific conditions in the near future.

Keywords: 3D cell culture models, Biofabrication, Disease modeling, Drug screening, Epithelial barriers, Microengineered tissues, Organ-on-a-chip, Organoids


de Goede, M., Chang, L., Dijkstra, M., Obregón, R., Ramón-Azcon, J., Martínez, Elena, Padilla, L., Adan, J., Mitjans, F., García-Blanco, S.M., (2018). Al2O3 Microresonator based passive and active biosensors ICTON 2018 20th International Conference on Transparent Optical Networks , IEEE Computer Society (Bucharest, Romania) , 8473820

Al2O3 microresonators were realized for sensing applications of both passive and active devices. Passive microring resonators exhibited quality factors up to 3.2×105 in air. A bulk refractive index sensitivity of 100 nm/RIU was demonstrated together with a limit of detection of 10-6 RIU. Functionalizing their surface allowed for the label-free detection of the biomarker rhS100A4 from urine with a limit of detection of 3 nM. Furthermore, single-mode Al2O3:Yb3+ microdisk lasers were realized that could operate in an aqueous environment. Upon varying the bulk refractive index their lasing wavelength could be tuned with a sensitivity of 20 nm/RIU and a LOD of 3×10-6 RIU.


de Goede, M., Chang, L., Dijkstra, M., Obregón, R., Ramón-Azcon, J., Martínez, Elena, Padilla, L., Adan, J., Mitjans, F., García-Blanco, S.M., (2018). Al2O3 Mmicroresonators for passive and active sensing applications Sensors 2018 Optical Sensors , OSA - The Optical Society (Zurich, Switzerland) Part F110, 1-2

The Al2O3 waveguide technology was explored for sensing applications. Passive microring resonators with a quality factor in air of 3.2×105 were developed with a bulk refractive index sensitivity of ~100 nm/RIU and limit of detection of ~10-6 RIU. These were functionalized to detect the biomarker rhS100A4 from urine down to concentrations of 3 nM. Furthermore, Al2O3:Yb3+ microdisk lasers were realized that exhibited single mode lasing operation in water. Their lasing wavelength was tuned by varying the bulk refractive index and a bulk refractive index sensitivity of ~20 nm/RIU with a LOD of ~3×10-6 was achieved.


de Goede, M., Dijkstra, M., Obregón, R., Martínez, Elena, García-Blanco, S.M., (2018). High quality factor Al2O3 microring resonators for on-chip sensing applications Proceedings SPIE. Integrated Optics: Devices, Materials, and Technologies XXII SPIE OPTO , SPIE (California, USA) 10535, 7

Microring resonators find many applications for on-chip integrated optical sensors. Their spectral response contains resonance dips that shift due to variations of the optical path length of the microring probed. Numerous examples of such microring resonator sensors in the SOI, Si3N4 and SiON waveguide technologies have been reported for the detection of bulk refractive index variations and the label-free detection of biomarkers. Al2O3 is an alternative waveguide technology that exhibits low optical propagation losses, is transparent over a large spectral range extending from the visible to the mid-IR and permits co-doping with active rare-earth ions, which enables the co-integration of active devices on the chip. In this work an Al2O3 microring resonator sensor was developed for the label-free detection of protein biomarkers. The uncladded microring with a radius of 200 μm had a measured quality factor of 3.2 × 105 at 1550 nm. Submerging the devices in water decreased the quality factor to 45 × 103. This corresponds with propagation losses in the rings of 0.6 dB/cm and 5.7 dB/cm respectively. The bulk refractive index sensitivity of the sensor was determined by flowing NaCl dissolved in water in different concentrations. A sensitivity of 102.3 ± 0.5 nm/RIU with a corresponding limit of detection of 1.6 × 10-6 RIU was demonstrated for TM polarized light. High affinity human monoclonal antibodies mAb S100A4 were immobilized on the sensor to detect the S100A4 protein biomarker down to 12 nM concentrations. These results demonstrate the feasibility of this material for label-free optical biosensors.


Ojosnegros', Samuel, Cutrale, Francesco, Rodríguez, Daniel, Otterstrom, Jason J., Chiu, Chi Li, Hortigüela, Verónica, Tarantino, Carolina, Seriola', Anna, Mieruszynski, Stephen, Martínez, Elena, Lakadamyali, Melike, Raya, Angel, Fraser, Scott E., (2017). Eph-ephrin signaling modulated by polymerization and condensation of receptors Proceedings of the National Academy of Sciences of the United States of America 114, (50), 13188-13193

Eph receptor signaling plays key roles in vertebrate tissue boundary formation, axonal pathfinding, and stem cell regeneration by steering cells to positions defined by its ligand ephrin. Some of the key events in Eph-ephrin signaling are understood: ephrin binding triggers the clustering of the Eph receptor, fostering transphosphorylation and signal transduction into the cell. However, a quantitative and mechanistic understanding of how the signal is processed by the recipient cell into precise and proportional responses is largely lacking. Studying Eph activation kinetics requires spatiotemporal data on the number and distribution of receptor oligomers, which is beyond the quantitative power offered by prevalent imaging methods. Here we describe an enhanced fluorescence fluctuation imaging analysis, which employs statistical resampling to measure the Eph receptor aggregation distribution within each pixel of an image. By performing this analysis over time courses extending tens of minutes, the information-rich 4D space (x, y, oligomerization, time) results were coupled to straightforward biophysical models of protein aggregation. This analysis reveals that Eph clustering can be explained by the combined contribution of polymerization of receptors into clusters, followed by their condensation into far larger aggregates. The modeling reveals that these two competing oligomerization mechanisms play distinct roles: polymerization mediates the activation of the receptor by assembling monomers into 6- to 8-mer oligomers; condensation of the preassembled oligomers into large clusters containing hundreds of monomers dampens the signaling. We propose that the polymerization–condensation dynamics creates mechanistic explanation for how cells properly respond to variable ligand concentrations and gradients.

Keywords: Eph, Ephrin, Receptor tyrosine kinase, Gradients, Cell communication


Garreta, E., de Oñate, L., Fernández-Santos, M. E., Oria, R., Tarantino, C., Climent, A. M., Marco, A., Samitier, M., Martínez, Elena, Valls-Margarit, M., Matesanz, R., Taylor, D. A., Fernández-Avilés, F., Izpisua Belmonte, J. C., Montserrat, N., (2016). Myocardial commitment from human pluripotent stem cells: Rapid production of human heart grafts Biomaterials 98, 64-78

Genome editing on human pluripotent stem cells (hPSCs) together with the development of protocols for organ decellularization opens the door to the generation of autologous bioartificial hearts. Here we sought to generate for the first time a fluorescent reporter human embryonic stem cell (hESC) line by means of Transcription activator-like effector nucleases (TALENs) to efficiently produce cardiomyocyte-like cells (CLCs) from hPSCs and repopulate decellularized human heart ventricles for heart engineering. In our hands, targeting myosin heavy chain locus (MYH6) with mCherry fluorescent reporter by TALEN technology in hESCs did not alter major pluripotent-related features, and allowed for the definition of a robust protocol for CLCs production also from human induced pluripotent stem cells (hiPSCs) in 14 days. hPSCs-derived CLCs (hPSCs-CLCs) were next used to recellularize acellular cardiac scaffolds. Electrophysiological responses encountered when hPSCs-CLCs were cultured on ventricular decellularized extracellular matrix (vdECM) correlated with significant increases in the levels of expression of different ion channels determinant for calcium homeostasis and heart contractile function. Overall, the approach described here allows for the rapid generation of human cardiac grafts from hPSCs, in a total of 24 days, providing a suitable platform for cardiac engineering and disease modeling in the human setting.

Keywords: Cardiac function, Extracellular matrix, Gene targeting, Pluripotent stem cells


Lagunas, A., Sasso, B., Tesson, N., Cantos, C., Martinez, Elena, Samitier, J., (2016). Synthesis of a polymethyl(methacrylate)-polystyrene-based diblock copolymer containing biotin for selective protein nanopatterning Polymer Chemistry 7, 212-218

Protein patterning is of interest in high-throughput screening. Due to an increase in demand for further miniaturization of protein assays, block copolymers (BCPs) that can undergo large-area phase separation into nanometer-size domains have attracted great attention as substrates for protein nanopatterning. Here we report the synthesis of a polymethyl(methacrylate)-polystyrene-based diblock copolymer which, once spin-coated, is capable of self-segregating into cylindrical polystyrene (PS) domains. In this copolymer, the PS block was modified to introduce biotin below 10% molar in order to achieve molecular recognition of streptavidin. The PMMA matrix used to introduce poly(ethylene glycol) enabled us to obtain an antifouling environment that prevents unspecific protein adsorption outside the domains. The use of the biotin-streptavidin pair in this BCP makes it suitable for nanopatterning of other biotinylated proteins of interest for the purposes of cell biology, biosensors, and tissue engineering.


Lagunas, Anna, Martinez, Elena, Samitier, Josep, (2015). Surface-bound molecular gradients for the high throughput screening of cell responses Frontiers in Bioengineering and Biotechnology 3, Article 132

Chemical gradient surfaces are described as surfaces with a gradually varying composition along their length. Continuous chemical gradients have recently been proposed as alternative to discrete microarrays for the high throughput screening of the effects of ligand concentration in cells. Here we review some of the most recent examples in which gradients have been used to evaluate the effect of a varying ligand concentration in cell adhesion, morphology, growth and differentiation of cells, including some of our recent findings. They show the importance of the organization of ligands at the nanoscale, which is highlighted by abrupt changes in cell behavior at critical concentration thresholds.

Keywords: Cell Adhesion, Cell Differentiation, Cell growth, Cell morphology, Molecular gradient


Galan, Teresa, Lagunas, Anna, Martinez, Elena, Samitier, Josep, (2015). Fabrication of bioactive polypyrrole microelectrodes on insulating surfaces by surface-guided biocatalytical polymerization RSC Advances 5, (82), 67082-67088

Although promising, organic microelectronics lacks standard fabrication methods comparable to photolithography in terms of resolution. Here we propose a novel and easily scalable on-surface biocatalytical procedure for the fabrication of polypyrrole microelectrodes on insulating surfaces. Arrays of polypyrrole microelectrodes were obtained by surface-guided biocatalytical polymerization, achieving up to 5 [small micro]m in resolution and conductivities up to 3 S cm-1. The mild reaction conditions provided by the biocatalytical approach permit the entrapment of bioactive compounds during polymer synthesis. This system is convenient for drug release purposes, as demonstrated by the controlled release of entrapped biotin through electrical stimulation. These results pave the way for the application of polypyrrole microelectrodes produced through biocatalysis in the development of implantable devices for remotely controlled tissue interactions.


Estévez, M., Martínez, Elena, Yarwood, S. J., Dalby, M. J., Samitier, J., (2015). Adhesion and migration of cells responding to microtopography Journal of Biomedical Materials Research - Part A , 103, (5), 1659-1668

It is known that cells respond strongly to microtopography. However, cellular mechanisms of response are unclear. Here, we study wild-type fibroblasts responding to 25 μm2 posts and compare their response to that of FAK-/- fibroblasts and fibroblasts with PMA treatment to stimulate protein kinase C (PKC) and the small g-protein Rac. FAK knockout cells modulated adhesion number and size in a similar way to cells on topography; that is, they used more, smaller adhesions, but migration was almost completely stalled demonstrating the importance of FAK signaling in contact guidance and adhesion turnover. Little similarity, however, was observed to PKC stimulated cells and cells on the topography. Interestingly, with PKC stimulation the cell nuclei became highly deformable bringing focus on these surfaces to the study of metastasis. Surfaces that aid the study of cellular migration are important in developing understanding of mechanisms of wound healing and repair in aligned tissues such as ligament and tendon.

Keywords: Adhesion, Cell migration, Cell morphology, Focal adhesion kinase, Microstructures


Comelles, J., Hortigüela, V., Martínez, Elena, Riveline, D., (2015). Methods for rectifying cell motions in vitro: Breaking symmetry using microfabrication and microfluidics Methods in Cell Biology - Biophysical Methods in Cell Biology (ed. Wilson, L., Tran, P.), Academic Press (Santa Barbara, USA) 125, 437-452

Cell motility is an important phenomenon in cell biology, developmental biology, and cancer. Here we report methods that we designed to identify and characterize external factors which direct cell motions by breaking locally the symmetry. We used microfabrication and microfluidics techniques to impose and combine mechanical and chemical cues to moving fibroblasts. Gradients can thereby be engineered at the cellular scale and this approach has allowed to disentangle roles of the nucleus and protrusion activity in setting cell directions.

Keywords: Adhesion, Biological physics, Cell motility, Gradient, Ratchet


de Oñate, L., Garreta, E., Tarantino, C., Martínez, Elena, Capilla, E., Navarro, I., Gutiérrez, J., Samitier, J., Campistol, J.M., Muñoz-Cánovas, P., Montserrat, N., (2015). Research on skeletal muscle diseases using pluripotent stem cells Muscle Cell and Tissue (ed. Sakuma, K.), InTech (Rijeka, Croatia) , 333-357

The generation of induced pluripotent stem cells (iPSCs), especially the generation of patient-derived pluripotent stem cells (PSCs) suitable for disease modelling in vitro, opens the door for the potential translation of stem-cell related studies into the clinic. Successful replacement, or augmentation, of the function of damaged cells by patient-derived differentiated stem cells would provide a novel cell-based therapy for skeletal muscle-related diseases. Since iPSCs resemble human embryonic stem cells (hESCs) in their ability to generate cells of the three germ layers, patient-specific iPSCs offer definitive solutions for the ethical and histo-incompatibility issues related to hESCs. Indeed human iPSC (hiPSC)-based autologous transplantation is heralded as the future of regenerative medicine. Interestingly, during the last years intense research has been published on disease-specific hiPSCs derivation and differentiation into relevant tissues/organs providing a unique scenario for modelling disease progression, to screen patient-specific drugs and enabling immunosupression-free cell replacement therapies. Here, we revise the most relevant findings in skeletal muscle differentiation using mouse and human PSCs. Finally and in an effort to bring iPSC technology to the daily routine of the laboratory, we provide two different protocols for the generation of patient-derived iPSCs.

Keywords: Pluripotent stem cells, Myogenic differentiation, Disease modelling, Patient-specific induced pluripotent stem cells, Muscular dystrophy


Comelles, J., Caballero, D., Voituriez, ., Hortigüela, V., Wollrab, V., Godeau, A. L., Samitier, J., Martínez, Elena, Riveline, D., (2014). Cells as active particles in asymmetric potentials: Motility under external gradients Biophysical Journal , 107, (7), 1513-1522

Cell migration is a crucial event during development and in disease. Mechanical constraints and chemical gradients can contribute to the establishment of cell direction, but their respective roles remain poorly understood. Using a microfabricated topographical ratchet, we show that the nucleus dictates the direction of cell movement through mechanical guidance by its environment. We demonstrate that this direction can be tuned by combining the topographical ratchet with a biochemical gradient of fibronectin adhesion. We report competition and cooperation between the two external cues. We also quantitatively compare the measurements associated with the trajectory of a model that treats cells as fluctuating particles trapped in a periodic asymmetric potential. We show that the cell nucleus contributes to the strength of the trap, whereas cell protrusions guided by the adhesive gradients add a constant tunable bias to the direction of cell motion.


Oberhansl, S., Garcia, A., Lagunas, A., Prats-Alfonso, E., Hirtz, M., Albericio, F., Fuchs, H., Samitier, J., Martinez, Elena, (2014). Mesopattern of immobilised bone morphogenetic protein-2 created by microcontact printing and dip-pen nanolithography influence C2C12 cell fate RSC Advances 4, (100), 56809-56815

Dip-pen nanolithography and microcontact printing were used to fabricate mesopatterned substrates for cell differentiation experiments. A biotin-thiol was patterned on gold substrates and subsequently functionalised with streptavidin and biotinylated bone morphogenetic protein-2 (BMP-2). The feasibility of mesopatterned substrates containing immobilised BMP-2 was proven by obtaining similar differentiation outcomes compared to the growth factor in solution. Therefore, these substrates might be suitable for replacing conventional experiments with BMP-2 in solution.

Keywords: Bone morphogenetic protein-2, C2C12 cells, Dip-pen nanolithography, Micro contact printing


Garcia, A., Hortigüela, V., Lagunas, A., Cortina, C., Montserrat, N., Samitier, J., Martinez, Elena, (2014). Protein patterning on hydrogels by direct microcontact printing: application to cardiac differentiation RSC Advances 4, (55), 29120-29123

An extended microcontact printing technique to chemically pattern hydrogels is reported. The procedure employs standard polydimethylsiloxane stamps and requires minor pre-processing of the hydrogels by freeze-drying. Micropatterned Matrigel[trade mark sign] and gelatin hydrogels induce NIH-3T3 cell alignment and elongation. Furthermore, human embryonic stem cells cultured on fibronectin-patterned hydrogels display beating foci earlier than those cultured on non-patterned substrates.


Equipment

Micro and nanofabrication techniques:

  • Biomolecule gradients produced by microfluidics
  • Large-area nanostructured polymer surfaces produced by diblock copolymers
  • 3D microstructures on hydrogel materials
  • Mini-bioreactor for 3D cell culture

Characterization techniques:

  • Surface Plasmon Resonance (SPR) measurements on polymer materials
  • Atomic Force Microscope (AFM) expertise
  • Optical Microscopes (white light/epifluorescence)
  • Focused Ion Beam (FIB) / Scanning Electron Microscopy (SEM) of biological specimens

Equipment:

  • Biological safety cabinet (class II)
  • High precision syringe pumps
  • Peristaltic pumps
  • Access to the Nanotechnology Platform (IBEC Core Facilities): equipment for hot embossing lithography, polymer processing and photolithography, chemical wet etching, e-beam evaporation and surface characterization (TOF-SIMS)
  • Access to the Scientific and Technological Centers (University of Barcelona): equipment for surface analysis (XPS, AFM, XRD) and microscopy techniques (SEM, TEM, confocal)

Collaborations

  • Prof. Ángel Raya / Dr. Samuel Ojosnegros
    Center of Regenerative Medicine in Barcelona (CMRB), Barcelona
  • Prof. Eduard Batlle
    Institut de Recerca Biomédica (IRB), Barcelona
  • Prof. Pablo Loza
    Institut de Ciències Fotòniques (ICFO), Castelldefels (Spain)
  • Dr. Javier Ramón, IBEC
  • Dr. Elisabeth Engel, IBEC
  • Prof. Raimon Jané, IBEC
  • Prof. Josep Samitier, IBEC
  • Prof. Javier Santos, Dra. Maria Vicario
    VHIR, Barcelona (Spain)
  • Dr. Bruno Sarmento
    i3S – Instituto de Investigação e Inovação em Saúde, Porto, Portugal
  • Dr. Sonia García-Blanco
    University of Twente, Enschede (The Netherlands)
  • Dr. Fabio Variola
    University of Ottawa (Canada)
  • Dr. Daniel Riveline
    ISIS/IGBMC, Strasbourg (France)
  • Dr. Matthew Dalby
    University of Glasgow (UK)
  • Prof. Jordi Martorell
    Institut de Ciències Fotòniques (ICFO), Castelldefels (Spain)
  • Prof. José Antonio Plaza
    CNM-CSIC, Barcelona
  • Dr. Francesc Mitjans
    LEITAT, Barcelona

 

News/Jobs

Bioenginyera contra el càncer: investigadors IBEC reben finançament de La Caixa

Els investigadors de l’IBEC Elena Martínez, Xavier Trepat i Pere Roca-Cusachs es proposen entendre els processos que promouen la metàstasi en càncer colorectal utilitzant innovadores eines de bioenginyeria, com la bioimpressió i la microscòpia capaç de revelar forces a escala cel·lular.

Els resultats es traduiran en un dispositiu que recrearà l’ambient tumoral a partir de les cèl·lules canceroses derivades dels mateixos pacients, així com una nova tecnologia que permetrà visualitzar com les forces físiques afecten els nuclis de les cèl·lules en metàstasi. Per això, els investigadors reben finançament de la tercera edició de la convocatòria “Health Research Call” de la Fundació “La Caixa”.

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L’IBEC lidera tres nous projectes europeus

La bioenginyeria és una disciplina clau per a la medicina del futur i Europa n’és conscient. Prova d’això és que la Unió Europea (UE) ha concedit en els últims mesos la coordinació de tres nous projectes europeus a l’Institut de Bioenginyeria de Catalunya (IBEC) perquè segueixi combinant la medicina, la ciència i la tecnologia i contribueixi així a millorar la salut de les persones.

El primer és el projecte BRIGHTER, que està liderat per la Professora i investigadora principal del grup ‘Sistemes biomimètics per a l’enginyeria cel·lular’ de l’IBEC Elena Martínez. La UE recolza aquesta iniciativa en la que l´IBEC i els seus socis del consorci desenvoluparan una nova tècnica de bioimpressió 3D d’alta resolució capaç de fabricar cultius cel·lulars tridimensionals que en un futur podrien ser útils per produir òrgans artificials.

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Elena Martínez rep una beca de la «European Research Council» per portar la recerca al mercat

Elena Martínez, líder de grup a l’IBEC i professora de la UB, ha estat guardonada amb la prestigiosa beca «Proof of Concept» del Consell Europeu de Recerca (European Research Council, ERC per les seves sigles en anglès). Amb el seu projecte «GUT3D-PLATE», Martínez i el seu equip en el grup «Sistemes biomimètics per a l’enginyeria cel·lular» podran desenvolupar en profunditat la tecnologia per fabricar substrats de cultiu cel·lular en 3D que imitin la fisiologia intestinal a punt per comercialitzar.

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Un equip de recerca desenvolupa una minifàbrica de teixit cardíac humà

Un sistema desenvolupat per investigadors de l’Institut de Bioenginyeria de Catalunya (IBEC) i del Centre de Medicina Regenerativa de Barcelona (CMR[B]) és capaç de produir al laboratori teixits que simulen el comportament del cor humà. Els teixits produïts per aquest sistema de bioenginyeria podrien servir per a preavaluar la toxicitat de medicaments en el cor sense necessitat d’utilitzar models animals.

Les malalties cardiovasculars suposen actualment una de les primeres causes de mort a escala mundial. No obstant això, els factors que motiven o accentuen aquestes malalties del cor s’amaguen, a vegades, darrere d’elements no coneguts. Entre altres causes, els medicaments que són útils per a curar o pal·liar determinades malalties poden, al mateix temps, presentar efectes secundaris sobre altres òrgans com el cor, el que els experts coneixen com a cardiotoxicitat.

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L’IBEC lidera un projecte europeu per al desenvolupament d’una nova tècnica de bioimressió 3D d’alta resolució

Un grup d’experts de l’Institut de Bioenginyeria de Catalunya (IBEC) lidera el projecte europeu BRIGHTER (Bioprinting by light-sheet lithography: engineering complex tissues with high resolution at high speed), una iniciativa que busca desenvolupar un innovador sistema de bioimpressió 3D d’alta resolució que podria ajudar a produir teixits funcionals.

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El president del Consell Europeu d’Investigació visita l’IBEC

El president del Consell Europeu d’Investigació (ERC), Jean-Pierre Bourguignon, va visitar el passat 15 de maig l’Institut de Bioenginyeria de Catalunya (IBEC).

L’esdeveniment va ser inaugurat pel director de l’IBEC, Josep Samitier, qui va presentar una visió general de la investigació d’avantguarda portada que s realitza a l’Institut als camps de la bioenginyeria i la nanomedicina.

Posteriorment, els investigadors amb concessió de fons ERC que treballem a l’IBEC van explicar com aquestes subvencions han les seves carreres professionals, i establir un diàleg amb el president de l’ERC sobre el passat, el present i el futur del Consell Europeu d’investigació.

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Mètode sense motlles per a generar un model 3D de teixit intestinal mitjançant hidrogels

El grup Sistemes Biomimètics per enginyeria cel·lular, dirigit per Elena Martínez, ha desenvolupat un nou mètode per a generar teixit intestinal en 3D mitjançant l’ús d’hidrogels. Aquest nou model in vitro s’ha pogut millorar proporcionant a les cèl·lules un entorn fisiològicament realista, que inclou arquitectura tissular, interaccions cèl·lula-matriu i senyalització química, sense deixar de ser compatibles amb les tècniques estàndard de caracterització cel·lular.

Els teixits epitelials contenen microtopografies tridimensionals complexes que són essencials per a desenvolupar correctament la seva funció.

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Un investigador de l’IBEC guanya el Premi Pioner per la seva tesi doctoral

Jemish Parmar, del grup de Nanodispositius intel·ligents, ha estat guardonat amb el Premi Pioner en l’edició de 2018 per la seva tesi doctoral anomenada “Micromotors per aplicacions mediambientals”.

Des del seu llançament en 2014, els Premis Pioner reconeixen a investigadors que presenten una tesi doctoral amb resultats clarament orientats a l’explotació industrial o comercial. Jemish, el tercer estudiant de l’IBEC a guanyar un d’aquests prestigiosos guardons, va recollir ahir el seu premi en la cerimònia que es va celebrar en sala d’actes de la Secretària d’Universitats i Recerca de la Generalitat de Catalunya, juntament amb els altres tres seleccionats d’aquest any –del ICFO, CTFC i IGTP–.

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