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News U3

News U3

Microfluidic device that reproduces the blood-retinal barrier

The use of In vitro testing with living cells as an alternative to animal research has limitations like the difficulty to reproduce the interaction of cells. To overcome it, scientists are working on the development of systems that simulate and reproduce functions of tissues and organs in conditions very similar to reality. They are called organ-on-a-chip, which include microenvironments and microarchitectures that simulate the state of tissues and living organs.

Scientists of NANBIOSIS Unit 8 have published in an article, cover of the magazine “Lab on a Chip”, the “proof of concept” of a microfluidic device that reproduces the blood-retinal barrier, that is, a microchip that allows us to reproduce what happens ” in vivo ‘in the retina. This device can be an essential tool that revolutionizes experimentation ‘in vitro’.

José Yeste, researcher of the CIBER-BBN, explains that the micro device consists of several parallel compartments, in which different types of cells have been cultivated to emulate the structure of cellular layers of the retina. They are endothelial cells, that is, they form the internal part of the barrier, in contact with the blood capillaries, through which oxygen and nutrients reach the retina. In addition, it is also composed of neuronal cells (which form the neuroretina), and pigment epithelial cells, which constitute the outer layer. The compartments are interconnected in their lower part by a network of micro-grooves, so as to allow an intercellular communication through the exchange of signalling molecules between cells. Thus, cells can send their signals to others and interact, much like they would in a living organism. In addition, the micro device allows the endothelial cells to be subjected to the mechanical stimulus induced by the flow to emulate a more physiological microenvironment.

“Within the body, the endothelial cells that line the inside of blood vessels are subject to the mechanical stimulation of blood circulation. In cell cultures that do not reproduce this flow, the cells are as ‘lethargic’, and do not respond in the same way they would in real conditions, “explains Rosa Villa, Scientific Director of NANBIOSIS Unit 8 and leader of the group of Biomedical Applications of the Microelectronics Institute of Barcelona of the CSIC.

Scientists have evaluated the correct formation of the blood-retinal barrier by performing permeability, electrical resistance tests, as well as protein expression of tight junctions between cells. These tests were intended to verify that the barrier is well formed, that it has closed but maintains the natural permeability, sufficient to allow the passage of nutrients and oxygen, and that the cells are in contact and interact with each other.

This work has been developed in the ICTS NANBIOSIS, more specifically in Unit 8 of Micro-Nano Technology located in the IMB-CNM. It is also part of the results of the CIBER intramural project called Micro BRB: Microfluidic model of retinal neurovascular unit to identify new therapeutic targets in diabetic retinopathy (2016-2017) in wich also  participates Unit 3 of NANBIOSIS

Source: http://noticiasdelaciencia.com/not/27155/un-microchip-microfluidico-reproduce-la-barrera-de-la-retina-humana/

Article of reference:

A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood–retinal barrier. Jose Yeste, Marta arcía-Ramírez, Xavi Illa, Anton Guimerà, Cristina Hernández, Rafael Simó and Rosa Villa. DOI: 10.1039/C7LC00795GLab Chip, 2018, 18, 95-105

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Researchers of NANBIOSIS U3 find activators of a possible therapeutic target for the treatment of patients with diabetes and insulin resistance

Researchers of  NANBIOSIS U3: Synthesis of Peptides Unit participate in the identification of activators of of the mitochondrial protein Mitofusin 2, a possible therapeutic target for the treatment of patients with type 2 diabetes in collaboration with CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) and the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN).

Those researchers are led by Fernando Albericio (Scientific Director of Unit 3 of NANBIOSIS) at the University of Barcelona and Antonio Zorzano en el IRB Barcelona  have identified activators of the mitochondrial protein Mitofusin 2 for the treatment of type 2 diabetes. This protein is expressed at abnormally low levels in the tissues of patients with diabetes. “Thanks to the studies of phenotypic screening and validation studies in human cells, it has been possible to demonstrate the role of the protein Mitofusin 2 in the development of many of the alterations associated with diabetes”, explain those responsible for the work.

These studies have been possible thanks to the work of biologists and chemists from different CIBER areas and with experience in synthetic chemistry, molecular screening and functional analysis.

Article of reference:

Identification of New Activators of Mitochondrial Fusion Reveals a Link between Mitochondrial Morphology and Pyrimidine Metabolism. Miret-Casals L, Sebastián D, Brea J, Rico-Leo EM, Palacín M, Fernández-Salguero PM, Loza MI, Albericio F, Zorzano A. Cell Chem Biol. 2017 Dec 23. pii: S2451-9456(17)30428-2. doi: 10.1016/j.chembiol.2017.12.001.

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Posters presentation by NANBIOSIS Units in CIBER-BBN ANNUAL CONFERENCE 2017

Last 13 and 14 of November, CIBER-BBN  has celebrated its 11th Annual Conference in Hotel Santemar in Santander. In this conference there was a poster session with the participation of the following Units of NANBIOSIS. Special mention deserves Unit 1 with Neus Ferrer as Director and  Paolo Saccardo as Coordinator (in the picture):


U1. Protein Production Platform (PPP):

Engineering protein complexes as nano- or micro-structured vehicles or drugs for human and veterinary medicine. Ugutz Unzueta, Naroa Serna, Laura Sánchez-García, José Vicente Carratalá, Olivia Cano-Garrido, Mercedes Márquez, Paolo Saccardo, Rosa Mendoza, Raquel Díaz, Héctor, López-Laguna, Julieta Sánchez, Anna Obando, Amanda Muñoz, Andrés Cisneros, Eric Voltà, Aida Carreño, José Luis Corchero, Neus Ferrer-Miralles, Esther Vázquez, Antonio Villaverde.

Units  U1. Protein Production Platform (PPP) and U18. Nanotoxicology Unit:

Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles. Mireia Pesarrodona, Eva Crosa, Rafael Cubarsi, Alejandro Sanchez-Chardi, Paolo Saccardo, Ugutz Unzueta, Fabian Rueda, Laura Sanchez-Garcia, Naroa Serna, Ramón Mangues, Neus Ferrer Miralles, Esther Vázquez, Antonio Villaverde.

Units U3. Synthesis of Peptides UnitU6. Biomaterial Processing and Nanostructuring Unit, and U20. In Vivo Experimental Platform:

Synthesis of different length monodisperse COL-PEG-PEPTIDE to increase biodisponibility of multifunctional nanovesicles for Fabry’s desease. Edgar Cristóbal-Lecina; Daniel Pulido; Solène Passemard; Elizabet González-Mira; Jaume Veciana; Nora Ventosa; Simó Schwartz; Ibane Abasolo; Fernando Albericio and Miriam Royo.

Units U13. Tissue & Scaffold Characterization Unit and U17. Confocal Microscopy Service::

Preclinical behavior of medium-chain cyanoacrylate glue with two different surgical application forms for mesh fixation in abdominal wall repair. Gemma Pascual, Bárbara Pérez-Köhler, Marta Rodríguez, Claudia Mesa-Ciller, Ángel Ortillés, Estefanía Peña, Begoña Calvo, Juan M. Bellón.

Units U27. High Performance Computing and U8. Micro – Nano Technology Unit:

Inspiration and Expiration Dynamics in Acute Emotional Stress Assessment. Javier Milagro, Eduardo Gil, Jorge M. Garzón-Rey, Jordi Aguiló, Raquel Bailón.

U5. Rapid Prototyping Unit:

Poly-DL-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells. Ana de la Mata, Miguel Ángel Mateos-Timoneda, Teresa Nieto-Miguel, Sara Galindo, Marina López-Paniagua, Xavier Puñet, Elisabeth Engel, Margarita Calonge.

U6. Biomaterial Processing and Nanostructuring Unit:

Strategy for engineering myoglobin nano-traps for biomedical sensing technology. E. Laukhina, O. V. Sinitsyna, N. K. Davydova, V. N. Sergeev, A. Gomez, I. Ratera, C. Blázquez Bondia, J. Paradowska, X. Rodriguez, J. Guasch, Jaume Veciana.

Structure and nanomechanics of quatsome membranes. B. Gumí-Audenis, L. PasquinaLemonche, J.A. Durán, N. Grimaldi, F. Sanz, J. Veciana, I. Ratera, N. Ventosa and M.I. Giannotti

U7. Nanotechnology Unit:

Bioreceptors nanostructuration study for early detection of Alzheimer. José Marrugo, Dr. Samuel Dulay, Dr. Mònica Mir, Prof. Josep Samitier.

RGD dendrimer-based nanopatterns promote chondrogenesis and intercellular communication for cartilage regeneration. Ignasi Casanellas, Anna Lagunas, Iro Tsintzou, Yolanda Vida, Daniel Collado, Ezequiel Pérez-Inestrosa, Cristina Rodríguez, Joana Magalhães, José A. Andrades, José Becerra, Josep Samitier.

Long-range electron transfer between redox partner proteins. Anna Lagunas, Alejandra GuerraCastellano, Alba Nin-Hill, Irene Díaz-Moreno, Miguel A. De la Rosa, Josep Samitier, Carme Rovira, Pau Gorostiza.

U8. Micro – Nano Technology Unit:

Miniaturized multi-sensing platform for pH and Dissolved Oxygen monitoring in Organ-On-aChip systems. M. Zea, A. Moya, I. Gimenez, R. Villa, G. Gabriel.

Electrochemical characterization of SWCNTs based microelectrodes fabricated by inkjet printing. M. Mass, A. Moya, G. Longinotti, M. Zea, M. Muñoz, E. Ramon, L. Fraigi, R. Villa, G. Ybarra, G. Gabriel.

U9. Synthesis of Nanoparticles Unit:

In vivo imaging and local persistance of polymeric micro- and nanomaterials labelled with the near infrared dye IR820. Isabel Ortiz de Solórzano, Gracia Mendoza, Inmaculada Pintre, Sara García-Salinas, Víctor Sebastián, Vanesa Andreu, Marina Gimeno, Manuel Arruebo.

U10. Drug Formulation:

Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids. Santiago Grijalvo, Adele Alagia, Gustavo Puras, Jon Zárate, Judith Mayr, José Luis Pedraz, Ramon Eritja

U12. Nanostructured liquid characterization unit:

Perfluorocarbon-loaded Nanocapsules from Nano-emulsion Templates as Microbubble Precursors for Biomedical Applications. G. Calderó, A. González, M. Monge, C. Rodríguez-Abreu, M.J.García-Celma, C. Solans.

Biodistribution study of polymeric drug-loaded nanoparticles in murine model. Marta Monge, Aurora Dols, Stephane Fourcade, Aurora Pujol, Carlos Rodríguez-Abreu, Conxita Solans.

U16. Surface Characterization and Calorimetry Unit:

Behavior and a comparative study between tantalum and titanium alloy implant surfaces against bacterial adhesion. M.A. Pacha-Olivenza, M.L. González-Martín.

Bacterial adhesion on calcium ion-modified titanium implant surfaces. M.A. Pacha Olivenza, R. Tejero, M. Delgado-Rastrollo, M.L. González-Martín.

Bioactive coatings to promote tissue regeneration and ingrowth into 3D custom-made porous titanium endoimplants (COATREG-3D). Santos-Ruiz L; Granados JF; Ruiz F; Yáñez JI; González A; Cabeza N; Vida Y; Pérez-Inestrosa E; Izquierdo-Barba I; Vallet-Regí M; Rubio J; Orgaz F; Rubio N; González ML; Peris JL; Monopoli D; Becerra J.

U17. Confocal Microscopy Service:

Subcutaneous implantation of a biodegradable apatite/agarose scaffold: biocompatibility and osteogenesis characterization in a rat model. Natalio García-Honduvilla, Gemma Pascual, Miguel A. Ortega, Alejandro Coca, Cynthia Trejo, Jesús Román, Juan Peña, María V. Cabañas, Julia Buján, and María Vallet-Regí.

U25. NMR: Biomedical Applications I:

Dual T1/T2 NCP-based novel contrast agents for brain tumor MRI: a preclinical study. Suarez, S; Arias-Ramos, N; Candiota, AP; Lorenzo, J; Ruiz-Molina, D; Arús, C; Novio, F.

Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide. Ferrer-Font, L; Arias-Ramos, N; Lope-Piedrafita, S; Julià- Sapé, M; Pumarola, M; Arús, C; Candiota, AP.

U26. NMR: Biomedical Applications II:

Gated nanodevices for innovative medical therapies. Maria Alfonso, Irene Galiana, Beatriz Lozano, Borja Diaz de Greñu, Cristina de la Torre, Andrea Bernardos, Sameh El Sayed, Daniel MuñozEspin, Miguel Rovira, José Ramón Murguía, Manuel Serrano, Ramón Martínez-Máñez.

NANOPROBE: Gated sensing materials and devices for the detection of infectious diseases and urological cancer. Ángela Ribes, Luís Pla, Sara Santiago-Felipe, Alba Loras-Monfort, M.Carmen Martínez-Bisbal, Elena Aznar, Guillermo Quintás-Soriano, José Luis Ruiz-Cerdá, María Angeles.




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“a-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration”

Unit 1 of NANBIOSIS, Protein Production Platform (PPP), Unit 3, Synthesis of Peptides, Unit 20, In Vivo Experimental Platform and Unit 6, Biomaterial Processing and Nanostructuring Unit, have jointly developed the research conducted in relation with a CO2-based methodology for the one-step production of protein-nanoliposome conjugates as bio-active nanomaterials with therapeutic interest. The results have been published in Advanced Healthcare Materials: http://www.ncbi.nlm.nih.gov/pubmed/26890358

“a-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration I. Cabrera, I. Abasolo, J. L. Corchero, E. Elizondo,  P. Rivera, E. Moreno, J. Faraudo, S. Sala, D. Bueno, E. González-Mira, M. Rivas, M. Melgarejo, D. Pulido, F. Albericio, M. Royo, A. Villaverde, M. F. García-Parajo, S. Schwartz Jr., N. Ventosa,*, and J. Veciana,*

Lysosomal storage disorders (LSD) are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of macromolecules such as lipids, glycoproteins and mucopolysaccharides. For instance, the lack of alpha-Galactosidase A (GLA) activity in Fabry disease patients causes the accumulation of glycosphingolipids in the vasculature leading to multiple organ pathology.

Enzyme replacement therapy (ERT), which is the most common treatment of LSD, exhibits several drawbacks mainly related to the instability and low efficacy of the exogenously administered therapeutic enzyme. In this work, the unprecedented increased enzymatic activity and intracellular penetration achieved by the association of a human recombinant GLA to nanoliposomes functionalized with RGD peptides is reported. Moreover, these new GLA loaded nanoliposomes lead to a higher efficacy in the reduction of the GLA substrate named globotriasylceramide (Gb3) in a cellular model of Fabry disease, than that achieved by the same concentration of the free enzyme. The preparation of these new liposomal formulations by DELOS-SUSP, based on the Depressurization of a CO2-Expanded Liquid Organic Solution, shows the great potential of this CO2-based methodology for the one-step production of protein-nanoliposome conjugates as bioactive nanomaterials with therapeutic interest.

“a-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration”
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