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Nanotechnology, gene therapy, omics therapies and ‘big data’

Nanotechnology, gene therapy, omics therapies and ‘big data’ were the topics discussed in the Forum on Emerging Technologies oganized on May 8 by nanotechnology, gene therapy, omics therapies and ‘big data’ were the topics discussed in the I Forum on Emerging Technologies held on May 8, organized by the CIBER Internationalization Platform, of which the CIBERER, the CIBER-BBN and the CIBERES.

The objective of this event, structured in sessions of presentations and scientific debates about the types of technologies addressed, was to promote the exchange of ideas and scientific knowledge with the aim of generating new collaborations among the CIBER research groups  such as participation in transversal projects or the development of cutting-edge technologies.

NANBIOSIS was represented by Pablo Laguna (Unit 27, High Performance Computing), Laura Lechuga (Unit 4, Biodeposition and Biodetection Unit), José Luis Pedraz (Unit 10, Drug Formulation) and Rosa Villa (Unit8, Micro – Nano Technology Unit)

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Gene therapy in pseudohypoparathyroidism

In 1942, Albright and colleagues described the first hormone resistance syndrome, which they called pseudohypoparathyroidism (PHP) (1), patients had a specific phenotype consisting of short stature, central obesity, round face, short neck and brachydactyly, which is what that today we know like Albright Hereditary Osteodystrophy (AHO, Albright Hereditary Osteodystrophy).

Nanobiocel research group, coordinator of NANBIOSIS U10. Drug Formulation, is working on the project “Gene therapy in pseudohypoparathyroidism: experimental development based on CRISPR / CAS9 and non-viral vectors“. The objective of the project is to design and validate the ex vivo gene therapy protocol for the correction of known mutations in the GNAS gene, causing pseudohypoparathyroidism (PHP) type 1A and pseudoPHP, through the following operational objectives: (1) Validation of the model lymphoblasts (immortalized or not) for the application of gene therapy; (2) CRISPR / Cas trial design and vehicularization in non-viral vectors; (3) Identification and characterization of off-target insertions (if any) and (4) Confirmation through functional studies of the correct functioning of the protein obtained from the modified gene.
The project will be carried out by the following research groups: BioAraba of Molecular Epigenetics in rare diseases, led by Dr. Guiomar Pérez de Nanclares, in the OSI Araba – Txagorritxu, the group Nanobiocel, led by Jose Luis Pedraz at UPV/EHU, this group is part of CIBER-BBN and ICTS NANBIOSIS and the group of Professor Cesar Martin, Biofisika Institute (UPV/EHU, CSIC).
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I Forum on Emerging Technologies organized by CIBER

On May 8th, will take place in Madrid, at the Assembly Hall Ernest Lluch of the Instituto de Salud Carlos III, organized by CIBER Internationalization Platform (CIBER-BBN, CIBERER, CIBERES) the I Forum on Emerging Technologies.

The objective of this meeting is to promote the exchange of ideas and scientific knowledge among the CIBER research groups with the aim of generating new collaborations for participation in cross-cutting projects and the development of border technologies. The content of the forum, centered on the type of technology and possibilities it offers, is structured in a program of lectures and scientific debates whose final objective is the discussion and the joint generation of ideas. This first edition of the forum will be focused on Gene Therapy, Nanotechnologies and Omic Technologies-Big Data.

Some Units of NANBIOSIS will participate:

  • José Luis Pedraz, Scientific Director of  Unit 10 Drug Formulation, will speak of “Development of non-viral vectors for gene therapy“
  • Laura Lechuga, Scientific Director of Unit 4  Biodepositon and Biodetection, will talk about “Nanodispositive biosensors for advanced clinical diagnosis
  • Rosa Villa, Scientific Director of Unit 8 Micro–Nano Technology, Ramón Martínez, Scientific Director of Unit 26 NMR Biomedical Applications II and Esther Pueyo, researcher of U27 High Performance Computer will moderate the sessions.

 

Programme and registration details

 

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NANBIOSIS Unit 10 of Drug Formulation participates in the European Project Position II

Nanobiocel, the CIBER-BNN – UPV-EHU group, led by José Luis Pedraz, Scientific Director of NANBIOSIS-ICTS U10 “Drug Formulation Unit” participates in the Position II European project, coordinated by Philips Electronics Nederland.

The project, funded through the Horizon 2020 call with a global budget of more than 50 million euros, will be developed during three years with the participation of 48 partners. Its general objective is to innovate in the production processes in the field of health to obtain state-of-the-art catheters. It will also include innovative treatments, such as cell therapy, which guide small capsules with cells with a regenerative effect to stimulate the recovery of damaged cardiac areas during the infarction.

The Nanobiocel group will be responsible for carrying out the formulation of the cells in hydrogels, for administration through the catheter at the cardiac level, for the regeneration of heart tissue.

In the development of the project, NANBIOSIS U10 “Drug Formulation Unit ” will participate. This Unit, located in the Faculty of Pharmacy of the UPV / EHU, has the capacity to design and evaluate classic dosage forms and new forms of biotechnological drugs, DNA, RNA and vaccines, using different methodologies based on micro and nanomedicine. This last methodology, based on the microencapsulation of cells, peptides, proteins and, in general, of biotechnological products, as well as the development and design of non-viral vectors for gene therapy, is one of the greatest singularities of this unit. It has the most advanced equipment for micro and nanoencapsulation.

The Eurpean project under Grant Agreement Ecsel-783132- POSOTION II 2017-IA, seeks to reverse the nowadays obsolete production of catheters (in the last decade there have been no innovations in this field). This justifies, from a business point, the investment in new R & D lines. In addition, it will introduce open technology platforms to increase miniaturization, the integration of electronics, wireless communications and their encapsulation. These technology platforms will renew catheter-based interventions, improving performance and reducing current production costs. It also seeks to break the current monopoly of US companies in the development and production of smart catheters.

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NANBIOSIS ICTS invites groups and companies to discuss Smart Biomaterials and devices for Drug Delivery

On February 22nd, the National School of Health of the Carlos III Health Institute hosted the forum on Smart Biomaterials and biomedical devices for applications in drug delivery and regenerative medicine, organized by the ICTS Nanbiosis, an infrastructure shared by the CIBER-BBN and the Center of Minimally Invasive Surgery Jesus Usón (CCMIJU). This is the first groups/companies meeting organized by Nanbiosis, in which about 70 B2B meetings  were held.

The meeting brought together about 40 participants from 14 research groups (from the CIBER-BBN and the CCMIJU) and 10 companies, which discussed the latest advances in the research lines developed by the groups and platforms of Nanbiosis and on the needs and demands of the industry in smart biomaterials and devices for targeted drug delivery and regenerative medicine.

Jesus Izco, Coordinator of Nanbiosis, presented the new “Cutting-Edge Biomedical Solutions“, soon available on the ICTS website. These are integrated solutions to advanced challenges in nanomedicine, biomaterials, medical device, and diagnostic that can be developed by several units under a  one-stop shop model, optimized with the experience and scientific and technical knowledge of the research groups of excellence that manage the involved units. Some of the Cutting-edge biomedical solutions presented in the meeting were preclinical validation of biomaterials, mechanical and surface characterization, biocompatibility and studies of biofilm formation and infections.

The CIBER-BBN prsentations were: “Instructive materials for regenerative medicine” by Miguel Ángel Mateos (NANBIOSIS U5 IP: Elisabeth Engel); “Molecular biomaterials for drug delivery and biomedical applications” byNathaly Veronica Segovia (NANBIOSIS U6 / IP Jaume Veciana and Nora Ventosa); “Advances with micro-nano technologies for in vitro devices and point of care” by Rosa Villa (NANBIOSIS U8 ); “Development of new dosage forms for advanced therapies based on new biomaterials” by José Luis Pedraz (NANBIOSIS U10); “Contact lenses functionalized for the prevention of corneal infections” by Jordi Esquena (NANBIOSIS U12 / IP Carlos Rodríguez); “Combined in-silico and in-vitro models of the cell microenvironment and drug delivery effects in cancer and tissue engineering applications” by Fany Peña (NANBIOSIS U13 / IP Miguel Á. Martínez); “Surface of the biomaterial: the first contact with our body” by  Marisa González (NANBIOSIS U16 ); “Use of biomaterials for the repair of soft tissue defects” by Bárbara Pérez Khöler (NANBIOSIS U17 / IP J M. Bellón and Gemma Pascual); “Controlled release systems based on mesoporous materials with molecular doors for applications in therapy and diagnosis” by Ramón Martínez Máñez (NANBIOSIS U26); “New intelligent devices and biomaterials for the treatment of pathologies of the retina and the nervous system” (Eduardo Fernández); and “Near-infrared responsive scaffolds for biomedical applications” (Nuria Vilaboa).

On the part of the CCMJU, the presentations were the following: “Application of Mesenchymal Stem Cells in preclinical models for surgical and cardiovascular research” by Javier García Casado (NANBIOSIS U14); “Regenerative medicine in animal models of cutaneous healing and diabetic models” by Beatriz Moreno (NANBIOSIS U19); “Preclinical studies of biomaterials” by Idoia Díaz-Güemes (NANBIOSIS U21 /IP: FM Sánchez Margallo); “Porcine model of myocardial infarction as a translational research platform in regenerative medicine” by Verónica Crisóstomo (NANBIOSIS U24).

In the turn of the companies, they presented some collaboration opportunities AJL, i-Vascular, Praxis Pharmaceutical, Technical Proteins Nanobiotechnology and REGEMAT 3D; and they also participated in the Rovi, Viscofan, Biomag and Biogelx Laboratories forum.

These meetings, where links are established between research groups and companies, address issues of business and scientific interest, allowing direct contacts between researchers and business managers.

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Cryopreservation of stem cells

Scientific Reports of the Nature Publications Group has recently published the article ‘Cryopreservation of human mesenchymal stem cells in an allogeneic bioscaffold based on platelet rich plasma and synovial fluid’. This research is part of the doctoral thesis of Haritz Gurruchaga, belonging to the NanoBioCel group of CIBER-BBN and UPV / EHU, which is focused on the optimization of the storage processes of encapsulated cells through slow cryopreservation. The thesis is being co-directed by  José Luis Pedraz and Jesús Ciriza, Scientific Director and Scientific Coordinator of NANBIOSIS Unit 10 Drug formulation.

The work is focused on the optimization of the storage processes of encapsulated cells through slow cryopreservation. Mesenchymal stem cells are being increasingly used for the treatment of various diseases

For further information

Article of reference:

Haritz Gurruchaga, Laura Saenz del Burgo, Ane Garate, Diego Delgado, Pello Sánchez, Gorka Orive, Jesús Ciriza, Mikel Sánchez, José Luis PedrazCryopreservation of Human Mesenchymal Stem Cells in an Allogeneic Bioscaffold based on Platelet Rich Plasma and Synovial FluidScientific Reports 7, Article number: 15733 (2017) DOI: 10.1038/s41598-017-16134-6

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Therapeutic approaches with CRISPR for albinism

Preclinical Development of CRISPR- based non-viral therapeutic approaches in existing cellular and animal models of Albinism, (NanoCripsAlbino Therapy)  is a multidiciplinar project to study ways to bring genetic editing tools to target cells to develop therapeutic strategies that can be used to treatment. The project, participated by Lluís Montoliu (CIBERER) and José Luis Pedraz (CIBER-BBN) and will financed by the Internationalization Platform of CIBER-BBN/ER/RES- with € 50000.

José Luis Pedraz is the Scientific Director of NANBIOSIS Unit 10 Drug formulation and PI of the CIBER-BBN NANOBIOCELL group, experst in de development of micro and nanoparticles to formulate new active principles based on peptides, proteins… and coming from new technologies such as Crispr/Cas technology. Specially in this project as Dr. Pedraz explains “We will contribute with our know-how in the development of non-viral particles based on lipid components to attach them to the CRISPR system and release them taking them to the target cell to correct the genetic defect”

Researchers have carried out a video to expose the objectives of the new project.

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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):

Posters:

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 Unit, U6. 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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New gelatine devices that mimic the body’s activity in bone regeneration

The NanoBioCel Group, Coordinator of Unit 10 of NANBIOSIS has led the development of new scaffolds (such as burns, trauma or tumour extractions), to regenerate critical bone defects that, in addition to physical support, offers the opportunity to release growth factors temporarily replacing the bone matrix and aiding the regeneration of bone tissue.

In order to make the material biodegradable, and reduce the risk of rejection, “we use a collagen derivative, a gelatine that is produced by processing collagen, since it has been found to be less cytotoxic than collagen itself, but maintains the properties we were looking for”, explains Pello Sánchez, member of the NanoBioCel group. In addition, for the polymerization of gelatine proteins and scaffold cohesion, they used a molecule that is extracted from the fruit of gardenia, genipina, “because it has a lower toxicity to the cells.”

All the tests and processes carried out to know the properties, biocompatibility and possible cytotoxicity of the scaffolds have been satisfactory. Preclinical studies have been performed on animals with promising results, which are in the process of being published. The group is trying now to improve what has been achieved to date, such as introducing other elements such as calcium, or other growth factors, that improve regeneration.

The project is part of a new line of research promoted by Drs. Gorka Orive and José Luis Pedraz, whose research group NanoBioCel of the Laboratory of Pharmacy and Pharmaceutical Technology of the UPV / EHU and CIBER-BBN coordinates Unit 10 of NANBIOSIS, used in the research. They also have counted with the collaboration of UCA (Unit of Arthroscopic Surgery), and the work of the company AGRENVEC, which was the supplier of the growth factors.

 

Bibliographic referenc

Sánchez, J.L. Pedraz, G. Orive .. Biologically active and biomimetic dual gelatin scaffolds for tissue engineering. International Journal of Biological Macromolecules, 98: 486-494 (2017). DOI: 10.1016 / j.ijbiomac.2016.12.092.

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New treatments for degenerative diseases of the retina

The final meeting of the TERET project took place last March, an initiative within the RETOS public-private collaboration initiative of the Ministry of Economy, Industry and Competitiveness funded with almost € 1 million. The project has been carried out over the past three years to develop new treatments for degenerative diseases of the retina, focusing specifically on age-related macular degeneration (AMD), diabetic retinopathy ( RD) and retinitis pigmentosa.

Unit 10 of ICTS NANBIOSIS has participated in carrying out the pharmaceutical formulation of the active principles, including the synthesis, chemical physical characterization and stability of the formulations over time, evaluation of the silencing capacity and viability of the formulations used in cellulare crops, together with the CIBER-BBN groups led by José Luis Pedraz (University of the Basque Country), Ramon Eritja (IQAC-CSIC) and Eduardo Fernández (U. Miguel Hernández de Elche) and the biotechnology companies Sylentis , LeadArtis and Leitat.

Gene silencing solutions have been used as a basis for this project through the use of interfering RNA (siRNA) nd multivalent antibodies in Trimerbody format.

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