The Biomimetic systems for cell engineering group is a junior group under IBEC’s Tenure Track scheme.
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.
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.
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
Silvia Marset Gomis | Masters Student
Valentina Serrano Cruz | Masters Student
Daniel Vera Ibañez | Visiting Researcher
|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|
|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|
|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|
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
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
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
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
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
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
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
Martinez, Elena, St-Pierre, Jean-Philippe, Variola, Fabio, (2019). Advanced bioengineering technologies for preclinical research Advances in Physics: X 4, (1), 1622451
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
- 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
- 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)
- 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
- Dr. Francesc Mitjans
Elena Martínez, group leader at IBEC and professor at the University of Barcelona (UB), is interviewed for the Big Vang section of La Vanguardia expaining her project to develop organs on a chip to improve the survival of patients with colorectal tumor metastases.
IBEC researchers Elena Martínez, Xavier Trepat and Pere Roca-Cusachs aim to understand the processes that promote metastasis in colorectal cancer using innovative bioengineering tools, such as bioprinting and microscopy capable of revealing forces at the cellular level.
The results will be translated into a device that will recreate the tumor environment from cancer cells derived from patients, as well as a new technology that will allow to visualize how physical forces affect the nuclei of metastatic cells.
Bioengineering is a core discipline for the medicine of the future, and Europe knows that. Proof of this is that the European Union (EU) has granted during the last months the coordination of three European projects to the Institute for Bioengineering of Catalonia (IBEC) to continue combining medicine, science and technology with the aim of improving people’s health.
The first one is the BRIGHTER project that is led by Professor Elena Martínez, the head of the ‘Biomimetic Systems for Cell Engineering’ group. The EU has contributed to this initiative that will be used by the consortium partners to develop an innovative high resolution 3D bioprinting technology able to fabricate 3D cell culture substrates which could be useful to produce artificial organs in the future.
Elena Martínez, Group Leader at IBEC and UB Professor, has been awarded the prestigious “Proof of Concept” grant of the European Research Council (ERC). With her “GUT3D-PLATE” project, Martínez and her team at the “Biomimetic systems for cell engineering” group will further develop technology to fabricate ready-to-commercialize 3D cell culture substrates mimicking the intestinal physiology.
A system developed by researchers from the Institute for Bioengineering of Catalonia (IBEC) and the Centre of Regenerative Medicine in Barcelona (CMR[B]) is capable of producing tissues in a laboratory that simulate the behaviour of the human heart. The tissues produced by this bioengineering system could be used to pre-evaluate the toxicity of drugs in the heart without using animal models.
Cardiovascular diseases are currently one of the leading causes of death worldwide. However, the factors that motivate or accentuate such heart diseases sometimes hide behind relatively unknown elements. Among other causes, drugs that are useful for curing or alleviating certain diseases can, at the same time, have side effects on other organs such as the heart, which experts refer to as cardiotoxicity.
During the last decade, intestinal organoids have emerged as a crucial tool to study intestinal biology in vitro. However, their sphere-like geometry limits the access to the organoid’s lumen hampering their use in many functional experiments where independent access to the different sides of the epithelium is required.
A group of experts at Institute for Bioengineering of Catalonia (IBEC) lead the European project BRIGHTER (Bioprinting by light-sheet lithography: engineering complex tissues with high resolution at high speed), an initiative to develop an innovative and high resolution 3D bioprinting technology able to produce functional tissues.
The President of the European Research Council, Jean-Pierre Bourguignon, visited last May 15th the Institute for Bioengineering of Catalonia (IBEC).
The event was inaugurated by IBEC’s Director, Josep Samitier, who presented an overview on the cutting-edge research carried out at the institute in the fields of bioengineering and nanomedicine.
Afterwards, ERC Grantees working at IBEC had the opportunity to explain the impact of ERC grants on their professional careers and established a dialogue with ERC President on the past, present and future of the European Research Council.
The Biomimetic systems for cell engineering group has developed a new method to generate 3D intestinal tissue using hydrogels. This new in vitro model has been improved by providing cells with a more physiologically realistic environment, including tissue architecture, cell-matrix interactions and chemical signalling while remaining compatible with standard cell characterization techniques.
Epithelial tissues contain complex three-dimensional microtopographies that are essential for their proper performance. These 3D microstructures provide cells with the physicochemical and mechanical signals needed to guide their self-organization into functional tissue structures and are key to their proper functioning.