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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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NANOMOL, Research Group Coordinator of Unit 6 of NANBIOSIS, accredited with TECNIO certification

NANOMOL, the research group coordinating ICTS “NANBIOSIS” Unit 6, has been accredited with the TECNIO certification as a Technology Developer Organization, until 2019. This TECNIO certification was created by the Government of Catalonia, through ACCIÓ. This certification supports the most qualified agents involved in technology transfer processes, allows companies to access advanced R&D and develop new products and services, and increases the scope of technology projects by finding the most suitable technology partners & suppliers.

About Nanomol (ICMAB-CSIC/CIBER-BBN)

NANOMOL is a research group depending on the Institute of Material Science of Barcelona from CSIC, with wide expertise and recognized excellence in the synthesis, processing and study of molecular and polymeric materials with chemical, electronic, magnetic and biomedical properties. NANOMOL is also a member of Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and of the technology transfer network TECNIO from ACC1Ó-Generalitat de Catalunya. The development by Nanomol of the different prototypes of nanocapsules will be performed in the ICTS “NANBIOSIS”, more specifically by the Biomaterial Processing and Nanostructuring Unit (U6) of the CIBER in Bioengineering, Biomaterials & NanomedicIne located at the ICMAB-CSIC.

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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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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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Novel synthetic routes as potential multifunctional theranostic nanodevices

Carlos Rodriguez-Abreu, Scientific Director of NANBIOSIS Unit 12 is co-author of the publication “Novel synthetic routes of large-pore magnetic mesoporous nanocomposites (SBA-15/Fe3O4) as potential multifunctional theranostic nanodevices” by “Journal of Materials Chemistry B”.

For further information

 

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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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ISO 9001:2008 certification of Quality Management System to NANBIOSIS U20

The Area of Functional Validation & Preclinical Research of CIBBIM-Nanomedicine has recently obtained the ISO 9001:2008 certification of Quality Management System.

Functional Validation & Preclinical Research (FVPR), led by Dr. Ibane Abasolo, Scientific Coordinator of Unit 20 of NANBIOSIS “In Vivo experimental Platform“,  was created in 2007 as part of the  CIBBIM-Nanomedicine’s technological offer. The objective of FVPR is to provide services to the different research groups of the mother institutions (VHIR and CIBER), as well as to external companies or groups, to evaluate the effectiveness and toxicity of new therapeutic agents or targets, whether they are nanotechnology-based or not. To this end, it has an  “in vivo Experimentation Platform with three differentiated sections (i) Experimental Animal Models, (ii) Molecular Imaging, and (iii) Preclinical Histology) and an “in vitro Experimentation Platform.”

The certification audit was carried out in May 2017 by the certification company TÜV Rheinland and the compliance with the standard was reviewed and that a Quality Management System based on continuous improvement was implemented. The certificate has been issued after the certification process already had been reviewed and approved by the head of the certification body. Now, FVPR is already implementing the transition from this ISO9001:2008 to ISO9001:2015, which will be audited in June of this year.

The ISO 9001 Standard is the most widespread Quality Management tool worldwide, with over one million certificates in 175 countries. The main objective of the standard is to increase customer satisfaction through continuous improvement processes. It is designed so that the organizations that apply it can guarantee their ability to offer services that meet the requirements of their customers. This international standard promotes the adoption of a process-based approach when the effectiveness of a quality management system is developed, implemented and improved, based in turn on the PDCA (Plan, Do, Check, Act) continuous improvement cycle.

The main benefits derived from ISO 9001 certification for organizations are: systematization of operations, improvement of internal organization, generation of a higher level of confidence in the internal and external environment, increased competitiveness, guarantee of compliance with legislation and regulations related to products and services, among others

For further information

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Improving biomaterials imaging for nanotechnology: rapid methods for protein localization at ultrastructural level

New publication of Tony Villaverde, Scientific Director of Unit 1 of NANBIOSIS acepted by Biotechnology Journal: The preparation of biological samples for electron microscopy is material- and time-consuming because it is often based on long protocols that also may produce artifacts. Protein labeling for transmission electron microscopy (TEM) is such an example, taking several days. However, for protein-based nanotechnology, high resolution imaging techniques are unique and crucial tools for studying the spatial distribution of these molecules, either alone or as components of biomaterials. In this paper, we tested 2 new short methods of immunolocalization for TEM, and compared them with a standard protocol in qualitative and quantitative approaches by using four protein-based nanoparticles. We reported a significant increase of labeling per area of nanoparticle in both new methodologies (H=19.811; p<0.001) with all the model antigens tested: GFP (H=22.115; p<0.001), MMP-2 (H=19.579; p<0.001), MMP-9 (H=7.567; p<0.023), and IFN-γ(H=62.110; p<0.001). We also found that the most suitable protocol for labeling depends on the nanoparticle’s tendency to aggregate. Moreover, the shorter methods reduce artifacts, time (by 30 %), residues and reagents hindering, losing, or altering antigens, and obtaining a significant increase of protein localization (of about 200 %). Overall, this study makes a step forward in the development of optimized protocols for thehigh resolution imaging techniques  high resolution imaging techniques within new biomaterials.

 

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Polyurethane and polyurea nanoparticle (PUUa), improves cancer therapy

The national consortium led by the research group of Addressing and Drug Release CIBBIM – Nanomedicine of the Vall d’Hebron Research Institute (VHIR) and led by Dr. Ibane Abasolo, Scientific Coordinataror of Unit 20 of NANBIOSIS, has shown improvement in the effectiveness and specificity of targeted therapy against cancer through the use of polyurethane-polyurea nanocapsules (PUUa), a nanoparticle with a proven targeted release, very useful for drugs with a high level of toxicity and low specificity of distribution. This nanoparticle has been developed by the research section of the Catalan company EcopolTech and Unit 20 of ICTS Nanbiosis has participated in vivo nanoparticle biodistribution assays, following the tissue accumulations of fluorescently labeled nanoparticles by means of the IVIS-Spectrum equipment. 

The study was based on the encapsulation of the drug Plitidepsin produced and patented by the Spanish pharmaceutical company PharmaMar SA. This drug, which was found in a marine invertebrate of Mediterranean origin and has proven efficacy in laboratory studies, also has a hydrophobic nature that makes its use in humans difficult. The nanoparticle PUUa, by covering the drug, improves biodistribution and reduces the toxicity of the drug, in addition to dramatically reducing the concentration necessary for its therapeutic function. Thus, it potentially increases the use of Plitidepsin in therapy for several types of cancer.
The nanocapsule is based on a shell made of, an RGD peptide to direct the nanoparticles to tumor cells and other fractions that ensure that the drug is released in environments with a high content of glutathione, a molecule that is found in high concentrations inside the tumor cells. Once inside the cell, the drug content is released and therapeutic function begins, highly effective in glioblastoma, colorectal cancer and breast cancer.

The research and synthesis of this nanocapsule has been carried out in collaboration with the Biomedical Research Institute, the CIBBER-BBN, and the companies Ecopol Tech SL and PharmaMar SA.

The importance of nanomedicine in cancer therapy:
In nanomedicine, a nanocapsule refers to an organic and biodegradable nanometric container that contains other molecules inside it, to be released once they reach their destination. In the case of cancer treatment, nanocapsules contain drugs that are usually hydrophobic and if they are administered naked (or without being wrapped by the nanocapsule), they are vulnerable to detection and digestion by macrophages – which reduces the effective accumulation of the drug in the tumor cells-, in addition to presenting a high toxicity both for the tumor cells of interest and for the healthy cells of the individual. These immunological barriers cause the administration at high concentrations of the drug chosen for the therapy, which leads to the known side effects of chemotherapy and the appearance of resistance.

Encapsulation can solve these problems: it prevents the elimination of drugs by macrophages, they circulate for a longer time through the blood flow, and they have improved permeability and retention. All because they are more specific covers and less toxic to the human body. Some of these nanomedicines are already being used in oncological patients, such as Myocet ™, DaunoXome ™, Depocyt ™, Abraxane ™, Genexol- * PM ™, and more recently, Onivyde ™: and all have improved the survival of cancer patients in a significative way.

And the research goes further, since the CIBBIM – Nanomedicine Pharmacological Surveillance and Release group of the VHIR has been working for ten years to bring the nanomedicines in development closer to patients and is currently working on several European projects in which several studies are being studied. nanoparticles for the treatment of pancreatic cancer, colorectal and breast cancer, Ewing sarcoma and Fabry minority disease.

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