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News U10

News U10

New Equipment available for the Regenerative Medicine Research Line of the U10 of NANBIOSIS

The Unit 10 of Drug Formulation of the ICTS NANBIOSIS coordinated by the CIBER-BBN NanoBioCel group directed by Jose Luis Pedraz, which belongs to the University of the Basque Country, has been present at the signing of the agreement that gives support by the Provincial Council of Alava within the framework of the Advance Pharma Development project, together with the research and technological development center TECNALIA. 

With this agreement, the NanoBioCel research group will receive in the next two years (2021-2023) a contribution of 650,000 €, which will allow the hiring of research personnel and the purchase of specific equipment for the regenerative medicine research line. The first equipment purchased to strengthen U10 in Bio-printing is the RegenHU Bioprinter: R-GEN 100, which will be located in the P3 Laboratory of the Lascaray Research Building. This bioprinter will bring two new technologies to the bioprinting techniques currently being used at U10: extrusion and droplet techniques. With RegenHU it will be possible to work with two new bioprinting processes: electrospinning and electrowriting. Electrospinning is a promising technique for the controlled release of drugs and electrowriting (electrostatic writing) will allow the construction of scaffolds with variable diameters in their design and elaboration.

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Results of the POSITION-II Project “A pilot line for the next generation of smart catheters and implants”

Cáceres, October 14th, 2021

POSITION II has received funding within the Electronic Components and Systems for European Leadership Joint Undertaking (ECSEL JU) in collaboration with the European Union’s H2020 Framework Programme (H2020/2014-2020) and National Authorities, under grant agreement Ecsel-783132-Position-II-2017-IA.

It promotes innovation in smart medical instruments and focuses in the next generation of smart catheters and implants by the introduction of open technology platforms for: miniaturization, in-tip AD conversion, wireless communication, MEMS transducer technology and encapsulation. These platforms are open to multiple users and for multiple applications.

POSITION II will enable the further development of the European R&D and manufacturing capability, not only encompassing the micro-fabricated device itself, but also the various value chains that they enable. Finally, by bringing smart catheters into the domain of high volume manufacturing, POSITION II will improve the quality of health-care at manageable cost.

The project, led by Philips Electronics Netherlands B.V, has been developed by 45 partners located in 12 different countries and has finished in September 2021. Within this large collaborative project, the NANBIOSIS units at CCMIJU have been involved in the validation of a novel catheter to administer encapsulated cell therapy to the heart. Also NANBIOSIS U10 Drug Formulation unit of CIBER-BBN and UPV/EHU , has participated being 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.

The results of the project are available on a video-format documentary that contains short interviews to the consortium partners on their participation. Specifically, CCMIJU has presented its work and results through a short interview to Dr. Verónica Crisóstomo, Coordinator of Cardiovascular Unit. The documentary can be found at https://vimeo.com/604674309/bd8b94050c

Further info about the project here: http://position-2.eu/

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Scientific Communication course

We want to invite you to a practical and short course of Introduction to Scientific Communication organized by CIBER-BBN and NanoBioCellGroup – NANBIOSIS U10 Drug Formulation Unit. The course will take place on the 5th (two hours from 9:00 am to 11:00 am) 6 and October 7 (4 hours from 9:00 a.m. to 1:00 p.m.) .-

The covid-19 pandemic has revealed the immense need to bring the world of science closer to citizens, so we are going to work on this soft skill through this course.

We have invited Inés Ortega, scientific communicator of the CIBER BBN, who will talk to us about how the dissemination activities score at the curricular level in the career of the research staff and will also address the issue of the Units of Scientific Culture (which are the intermediaries between the institutions and the citizenship to promote scientific culture). At the UPV / EHU through Euskampus Fundazioa, he will also talk about different tools to reach society. We will also have Dr. Enrique Pérez, an expert in communication and body language, with whom we will do a practical workshop on the construction of the story (for example, how to explain a scientific project to the general public) and the work of the staging.

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Characterization of encapsulated porcine cardiosphere-derived cells for cardiac regeneration.

Researchers of NANBIOSIS U10 Drug Formulation unit of CIBER-BBN and UPV/EHU and NANBIOSIS U14 Cell Therapy unit and U24 Medical imaging unit at CCMIJU have participated in a research that proposes the use of encapsulated cardiosphere-derived cells (CDC), obtained from heart tissue, as regenerative cell therapy.

The encapsulation of the cells has been carried out in NANBIOSIS Unit 10, as well as the characterization of the cells (both encapsulated and unencapsulated) for their application in regenerative medicine (cardiac regeneration); and unit 14 of NANBIOSIS has obtained the cell model used for the study “ – Explains Kaoutar Ziani Akrirout, research scientists of CIBER-BBN and NANBIOSIS Unit 10.

These cells are multipotent stem cells, which secrete growth factors capable of promoting revascularization and healing of infarcted tissue. However, the use of this therapy faces a great challenge, which is the survival and retention of these cells after their implantation in the infarcted area, since the heart is a tissue that is constantly contracting and expanding, which leads to the loss of these cells, as they are carried along by the bloodstream.

To solve the low retention of cells, members of the NanoBioCel research team, from the CIBER-BBN and attached to the Bioaraba Health Research Institute (IIS Bioaraba), in collaboration with researchers from the IIS Aragón and the CIBERCV, propose the encapsulation of the CDC of porcine origin within a three-dimensional alginate-poly-L-lysine-alginate matrix as a therapy for cardiac regeneration, since, thanks to this, the encapsulated cells will be able to remain adhered to the tissue for longer, giving them time to exercise their function. The final objective will be to verify its efficacy in swine infarction models.

The team has verified that the phenotypic characteristics, the gene expression profile, the ability to differentiate to other cell lines and the release of growth factors from these cells are not altered by the encapsulation process, essential aspects given that their preservation it is essential for cardiac regeneration. In addition, this procedure keeps them viable for a month, which would favor the possible regeneration of the tissue.

On the other hand, that a sustained release of growth factors is maintained in these cells suggests that the implantation of encapsulated CDCs will promote the formation of new blood vessels and, consequently, the regeneration of infarcted cardiac tissue.

The researchers suggest that encapsulated CDCs could be a highly interesting therapeutic alternative in the field of cardiac regenerative medicine.

Article of reference

Ziani K, Espona-Noguera A, Crisóstomo V, Casado JG, Sanchez-Margallo FM, Saenz-Del-Burgo L, Ciriza J, Pedraz JL. Characterization of encapsulated porcine cardiosphere-derived cells embedded in 3D alginate matrices. Int J Pharm. 2021 Apr 15;599:120454.[DOI

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Reversing pulmonary fibrosis has been achieved in murine models with peptide-loaded nanoparticles

A new study with participation of NANBIOSIS Unit 10 Drug Formulation unit of CIBER-BBN and UPV/EHU, has succeeded in preventing and reversing pulmonary fibrosis in experimental models with PLGA / PEI nanoparticles loaded with the GSE4 peptide. These results are the first step to study its possible antifibrotic effect in patients with idiopathic pulmonary fibrosis and other progressive fibrosing diffuse interstitial lung diseases that present altered telomere function.

NANBIOSIS unit 10 has been responsible for the design and manufacture of biodegradable nanoparticles loaded with the peptide.

The work is led by Rosario Perona and Leandro Sastre, researchers of CIBERER at the Biomedical Research Institute (CSIC/UAM), and Maria Molina-Molina, researcher at CIBERES and the Department of Pulmonology at the Bellvitge University Hospital. In addition, Guillermo Güenechea, from CIBERER at CIEMAT-IIS / FJD, and José Luis Pedraz, from CIBER-BBN and the University of the Basque Country have collaborated.

Idiopathic pulmonary fibrosis is a fatal fibrotic disease associated with aging with a median survival of 2 to 5 years. The disease usually appears around the age of 60, but there are familiar forms that can manifest at younger ages. Fibrosis appears as an aberrant healing response after alveolar damage and is characterized by the appearance of abnormal lung scarring, in which the restoration of epithelial integrity and tissue function is compromised. The mechanisms responsible for defective repair and regeneration are not well understood. However, recent studies suggest a possible role of accelerated aging and telomere shortening in the onset of the disease, mainly in familial forms.

The GSE4 peptide, of 11 amino acids, corresponds to an internal sequence of dyskerin, a protein that is part of the telomerase complex. GSE4 has protective effects on the cells of patients with the rare diseases dyskeratosis congenita and ataxia-telangiectasia, as it increases telomerase activity and cell growth and reduces DNA damage, oxidative stress and cell senescence.

The authors of the study, published in The FASEB Journal, used rat lung alveolar cells treated with a profibrotic agent, bleomycin, as a model. Expression of the GSE4 peptide or treatment with GSE4-PLGA / PEI nanoparticles causes a reversal of the inflammatory and fibrotic phenotype. There is an increase in telomerase activity, a decrease in DNA damage, and a decrease in inflammation and cell death. Furthermore, these cells show an inhibition in fibrosis.

In a rat model with bleomycin-induced pulmonary fibrosis, treatment with GSE4-PLGA / PEI nanoparticles has also increased telomerase activity and decreased DNA damage in alveolar cells. In both preventive and therapeutic protocols, GSE4-PLGA / PEI nanoparticles have prevented and attenuated lung damage and inhibited fibrosis. Histological analysis of the lungs of rats treated with bleomycin and GSE4-PLGA / PEI nanoparticles shows less fibrosis and inflammation and greater regeneration of the alveolar tissue, indicating the therapeutic efficacy of GSE4-loaded nanoparticles in this experimental pulmonary fibrosis model. .

This study supports the possibility of further investigating a potential curative treatment for patients with pulmonary fibrosis.

Reference article:

Pintado-Berninches, L., Montes-Worboys, A., Manguan-García, C., et al. “GSE4-loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage.” The FASEB Journal. 2021; 35: e21422. DOI: 10.1096/fj.202001160RR

(*) Explanation of the figure: Treatment with the profibrotic agent bleomycin decreases the number of cells that express the alveolar marker proSP-C (Bleo). Inoculation of GSE4-loaded nanoparticles into bleomycin-treated rats increases the number of cells expressing the marker, indicating alveolar regeneration.

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New Center for Research in Advanced Pharmaceutical Development

The NanoBioCel Research group, led by Jose Luis Pedraz, from CIBER-BBN and UPV/EHU, group that coordinates the Unit U10 Drug Formulation of NANBIOSIS -ICTS, together with the Provincial Council of Álava and the Center for Technological Research and Development TECNALIA, have launched last Thursday, January 21, the new Center for Research in Advanced Pharmaceutical Development, which will be located in the Lascaray Building, on the Álava campus of the UPV / EHU.

The objective of this center is to introduce new technologies in the pharmaceutical field and promote applied research in 3D Bio-printing, 3D Printing of medical devices and 3D Printing of new drugs.

This new center is a strategic and ambitious project, supported directly by the Provincial Council of Álava with a budget of € 2,500,000 that seeks to integrate the Álava region within the strategy proposed by the European Union in biosciences and technological development, sectors that have been boosted in the new investment initiative in response to the Coronavirus. This center is also a regional reference as a result of the leadership exercised by the NanoBioCel research group and a fruitful relationship of common projects to offer services to the pharmaceutical industry with Tecnalia2.

In the picture: Jose Luis Elejalde from Tecnalia, Javier Hernando from the Provincial Council of Alava, Pilar Garcia de Salazar, Lieutenant General Deputy and Provincial Deputy for Economic Development and Territorial Balance in the Provincial Council of Alava. Jose Luis Martin, Vice-Rector for Research of the UPV / EHU and Jose Luis Pedraz, IP NanoBioCel group.

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Non-viral mediated gene therapy in human cystic fibrosis airway epithelial cells recovers chloride channel functionality

Researchers of CIBER-BBN Units of NANBIOSIS: U29 Oligonucleotide Synthesis Platform (OSP) at IQAC_CSIC, led by Prof. Ramón Eritja and U10 Drug Formulation, at UPV-EHU, led by Prof José Luis Pedraz, are coauthors of an article published by International Journal of Pharmaceutics.

Gene therapy strategies based on non-viral vectors are currently considered as a promising therapeutic option for the treatment of cystic fibrosis (CF), being liposomes the most commonly used gene carriers. Niosomes offer a powerful alternative to liposomes due to their higher stability and lower cytotoxicity, provided by their non-ionic surfactant and helper components. In this work, a three-formulation screening is performed, in terms of physicochemical and biological behavior, in CF patient derived airway epithelial cells. The most efficient niosome formulation reaches 28% of EGFP expressing live cells and follows caveolae-mediated endocytosis. Transfection with therapeutic cystic fibrosis transmembrane conductance regulator (CFTR) gene results in 5-fold increase of CFTR protein expression in transfected versus non-transfected cells, which leads to 1.5-fold increment of the chloride channel functionality. These findings highlight the relevance of niosome-based systems as an encouraging non-viral gene therapy platform with potential therapeutic benefits for CF.

The article acknowledges U10 Drug Formulation, for the intellectual and technical assistance

Article or reference:

Non-viral mediated gene therapy in human cystic fibrosis airway epithelial cells recovers chloride channel functionality-Sainz-Ramos, M., Villate-Beitia, I., Gallego, I., A.L. Qtaish, N., Lopez-Mendez, T.B., Eritja, R., Grijalvo, S., Puras, G., Pedraz, J.L. International Journal of Pharmaceutics, 588, art. no. 119757, 2020. https://doi.org/10.1016/j.ijpharm.2020.119757

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Moore4Medical a project to accelerate innovation in electronic medical devices

The NanoBioCell group, led by Prof. Jose Luis Pedraz, participates in the European project Moore4medical. A project to accelerate innovation in emergencing medical devices with open tecnhology platforms. The NanoBiocel group, will focus on the lyophilization process of biopharmaceuticals and their use in microfluidic devices

The NanoBiocel research group of the University of the Basque Country / Euskal Herriko Unibertsitatea, which is part of the CIBER BBN and the ICTS Nanbiosis through the U10 Drug Formulation Unit, and led by Professor Jose Luis Pedraz of the Faculty of Pharmacy, participates in the European project Moore4medical, which aims to accelerate innovation in electronic and microfabricated devices for several emerging medical specialties. Specifically, the work of the NanoBiocel group will focus on optimizing the lyophilization process of biopharmaceuticals in microfluidic devices.
The three-year Moore4Medical project is funded by the public-private partnership ECSEL (Electronic Components and Systems for European Leadership), which manages a research and innovation program to strengthen the electronic components and systems sector to maintain to the European Union at the forefront of technological development. The total financing of the project amounts to € 68M, of which more than half a million have been awarded to the work of NanoBiocel.
In Moore4Medical, 68 partners participate (between private companies, universities and research institutions) from 13 countries and is led by the Dutch multinational Philips in its electronics and medical systems and service innovation divisions.

Microfluidic device
The NanoBioCell group will work, together with the Mondragón company microLIQUID, in the development of technology for integrating lyophilized drugs and their rehydration in a microfluidic device for their correct administration. The lyophilized drug will be integrated into the microfluidic device using specific techniques to ensure a good interaction between the fluid and the drug for delivery by the pump. The final objective is to design a system for the administration of drugs by parenteral route that is much more comfortable for patients and that improves the therapeutic compliance of treatments.
The microLIQUID company is a leading biotechnology company in the microfluidic technologies sector and will be in charge of the design and development of microfluidic modules.
In this work called ‘Drug Adherence’, integrated within the total project, the NanoBioCel group will team up with the Irish national institute Tyndall, the multinational pharmaceutical company AbbVie, the Fraunhofer Institute of Germany, the service innovation section of Philips, the company German Gaudlitz GmbH, specialist in polymers, the Karlsruhe Technological Institute in Germany and the HI Iberia company in Madrid.

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Ainhoa González Pujana, NANBIOSIS U10, 2019 best doctoral thesis award by the Bioaraba Research Health Institute

The Bioaraba Health Research Institute has awarded Ainhoa ​​González Pujana, a researcher at NanoBioCell and the Nanbiosis Platform through the U10 Drug Formulation (from CIBER-BBN and UPV-EHU), the award for the best doctoral thesis 2019 at the XXI Bioaraba Research and Innovation Conference, held last November 5 in Vitoria-Gasteiz.

Along with the recognition, the award consists of an economic endowment of € 1,000 in funds for R + D + i. The thesis, directed by Professor Rosa María Hernández and Dr. Edorta Santos Vizcaíno, has been carried out in the NanoBioCel group of the Faculty of Pharmacy of the University of the Basque Country (UPV / EHU). Under the title “Bioinspired three-dimensional multifunctional systems to enhance the therapeutic potential of mesenchymal stromal cells”, the thesis has focused on the design of biomimetic matrices that enhance the immunomodulatory effect of mesenchymal stem cells, as a therapeutic alternative for treatment of the immunological alterations that occur in diseases such as ulcerative colitis, Crohn’s disease or Lupus erythematosus.

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How to delay vision loss in hereditary retinal dystrophies? Looking for the most effective and economical pharmacological nanotherapy

Researchers from the CIBER-BBN and NANBIOSIS are participating in a new project that aims to achieve the most effective, specific and economical pharmacological nanotherapy that allows delaying the death of retinal cells and subsequent loss of vision in hereditary retinal dystrophy. retinitis pigmentosa, regardless of the genetic defect causing the disease.

In this project, coordinated by the researcher Regina Rodrigo, the ONCE and the Prince Felipe Research Center (CIPF) of Valencia collaborate, together with researchers from the CIBER of Rare Diseases (CIBERER) and the Manises Hospital in Valencia. On behalf of the CIBER-BBN, the scientific director, Ramón Martínez Máñez, together with Elena Aznar from the IDM-UPV group of the Polytechnic University of València, José Luís Pedraz, Gustavo Puras and Idoia Gallego, from the group of the University of the Basque Country and Nanbiosis.

The NANBIOSIS participation in the project will be through the U10 Drug Formulation unit (from @CIBERBBN and @upvehu), led by NanoBioCell Group and Prof. José Luis Pedraz and U26 NMR: Biomedical Applications II , led by IDM-UPV-UV Group, led by Prof. Ramón Martínez Máñez. Elena Aznar, researcher of CIBER-BBN at IDM-UPV-UV explained “We use the unit to characterize the nanoparticles. Through a solid phase NMR confirms that the molecular gate has been correctly attached to the surface of the nanoparticles“.

Retinitis pigmentosa is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision. Although it is considered a rare disease, it is the leading genetic cause of blindness in developed countries. So far there is no effective treatment, although there are various therapeutic approaches such as gene therapy, cell therapy, pharmacological therapy, optogenetics or electronic implants.

During the progression of the disease, an important inflammatory component has been observed that may contribute to its pathogenesis. In this sense, different anti-inflammatory strategies have been evaluated. The research group has successfully tested one of these strategies in preclinical models of retinitis pigmentosa. However, the implementation of this therapeutic strategy with nanocarriers as controlled release delivery systems would improve the mode of action of the administered drug, avoiding its degradation, increasing its half-life, stability or its availability in the retina. In this project, two types of nanocarriers will be used and their effect on the degenerative process in a murine model of retinitis pigmentosa will be evaluated.

  • PICTURE: Hematoxylin and eosin image showing that intravitreal blockade of the cytokine TNFα with Adalimumab-type monoclonal antibodies (ADA) reduces retinal degeneration, preventing the death of photoreceptors (RF) in the murine model of retinitis pigmentosa, rd10 mouse.
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