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3D printing biocompatible hydrogels

 

Researchers of Unit 5 of NANBIOSIS, in collaboration with colleagues from the University of Montpellier, have laid the groundwork for faster advances in 3D printing for regenerative medicine by creating a system of ink and matrices that offers a solid basis for tissue regeneration.

Due to their high water content, hydrogels are highly attractive biomaterials for 3D printing as efficient ‘surrogates’ for the extracellular matrix, onto which cells can be cultured. However, while they are relatively easy to produce using a method called extrusion printing, their stability and structural integrity can weaken when they’re in contact with biological fluids or extracellular matrices.

The Biomaterials for Regenerative Therapies group’s new method uses a hybrid bioink that doesn’t need any photochemical or organic reagent and which safe for use in vivo. Using a versatile and biocompatible method called sol-gel, this bioink can be used to print a peptide-functionalized hydrogel. It’s the first time sol-gel has been used for hydrogel inks, as all examples combining sol-gel and 3D printing have so far dealt either with inorganic constructs or with extrusion printing under nonbiocompatible conditions.

The new matrices work better than current ones because, as well as being biocompatible, certain essential processes such as hydrolysis occur during the printing process, resulting in a much stronger and more reliable structure. The researchers, who worked in collaboration with colleagues in France, were able to successfully seed them with mesenchymal stem cells, and are now looking at the possibility of encapsulating cells within the hybrid ink so that seeding can take place during the construction process.

As well as producing a stronger matrix, the combination of sol-gel chemistry and 3D printing means that the new method could be a promising way to quickly produce an unlimited number of customized, cell-laden, biocompatible structures. Not only that, but using several different hybrid bioinks could open the way to making multilayer and non-homogeneous biomaterials, mimicking the complexity of natural tissues even more closely.

The 3D scaffold fabrication was performed using the facilities of the platform of Production of Biomaterials and Biomolecules of the ICTS “NANBIOSIS”, more specifically by the U5 Unit of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the Institute for Bioengineering of Catalonia (IBEC).

 

Article of reference:

Echalier, R. Levato, M. A. Mateos-Timoneda, O. Castaño, S. Déjean, X. Garric, C. Pinese, D. Noel, E. Engel, J. Martinez, A. Mehdi & G. Subra (2017). Modular bioink for 3D printing of biocompatible hydrogels: sol–gel polymerization of hybrid peptides and polymers. RSC Adv., 2017, 7, 12231-12235.

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Unit 25 of NANBIOSIS and the research field of Protein Kinase CK2. 

Ana Paula Candiota and Carles Arús, Scientific Coordinator and Scientific Director of Unit 25 of NANBIOSIS, jointly with other GABRMN members, have recently published an interesting article in the journal Pharmaceuticals, (Special Issue An Updated View on an Emerging Target: Selected Papers from the 8th International Conference on Protein Kinase CK2). This article  is also co-authored by scientifics of a research group with renowned prestige in CK2 research field, the Protein Phosphorylation group, del Dipartimento di scienze biomediche (Università degli Studi di Padova).

This publication describes a study with the preclinical glioblastoma (GB) model and its treatment, centered in exploring the potential of other therapeutic (non-mutagenic) alternatives for preclinical GB. The results obtained suggest that Protein Kinase CK2 could be a suitable candidate target for GB treatment, which could be useful in combined treatments with temozolomide (TMZ), the standard of care currently used in clinics. Tumor-bearing animals under treatment were followed up with techniques of MRI, MRSI and DWI, and an interesting finding was the appearance of peritumoral brain edema in treated animals.

The acquisition and processing of MRI/MRSI/DWI data were performed in Unit 25 of NANBIOSIS

Article of reference:

Ferrer-Font, L.; Villamañan, L.; Arias-Ramos, N.; Vilardell, J.; Plana, M.; Ruzzene, M.; Pinna, L.A.; Itarte, E.; Arús, C.; Candiota, A.P. Targeting Protein Kinase CK2: Evaluating CX-4945 Potential for GL261 Glioblastoma Therapy in Immunocompetent Mice. Pharmaceuticals 2017, 10, 24.

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Bioengineering is being strengthened in Spain

Estefanía Peña, Scientific Coordinator of Unit 13 of NANBIOSIS explains her resarch in the program “En route with science” of Aragon Television.

Bioengineering consists in the application of the principles of engineering to the field of medicine. In the opinion of Estefanía, coordinator of the Division of Biomedical Engineering and deputy director of I3A (Institute of Research in Engineering of Aragon) Bioingineering is being strengthened in Spain.

“Our research develops mathematical models and computational reproduction, especially of cardiovascular diseases and the therapies to solve them. Fundamentally we work on atherosclerosis, which is the appearance and development of atheroma plaque (a cluster of cholesterol in the wall of an artery)

This is a field with a very important social impact (35% of the deaths in Europe are due to cardiovascular diseases and the annual European cost can be around almost two hundred billion euro), this is why we try to reduce the part of experimentation developing mathematical models, both to understand the biological process, and to design new devices as stems.”

For further information:

http://alacarta.aragontelevision.es/programas/en-ruta-con-la-ciencia/ Cap 45 Min.21:42-28:12

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Titania-coated gold nanorods with expanded photocatalytic response

New communication in the Journal Nanoscale, from the Royal Society of Chemistry by NFP Group, coordinator of Unit 9 of NANBIOSIS.

Jesús Santamaría, Scientific Director of Unit 9 of NANBIOSIS together with other authors of the Nanostructured Films and Particles (NFP) Group, coordinator of Unit 9 of NANBIOSIS, has published on February 7, 2017, a Communication in the Journal Nanoscale, from the Royal Society of Chemistry.

The syntheses of materials during the research have been performed by the Platform of Production of Biomaterials and Nanoparticles of the NANBIOSIS ICTS, more specifically by the Nanoparticle Synthesis Unit, as stated in the publication.

Gold nanorods coated with a uniform titanium dioxide nanoshell have been prepared and used as glucose-oxidase surrogates. Remarkably, this core–shell photocatalytic nanostructure has been able to induce complete oxidation of glucose at near room temperature (32–34 °C) in a wide range of pH values with the aid of a near-infrared (NIR) irradiation source. In contrast, the uncoated gold nanorods exhibit negligible photo-oxidation response under identical experimental conditions thereby proving the photoactivity of the titania shell towards glucose oxidation. The process takes place via in situ photo-generation of singlet oxygen or hydroxyl radicals as reactive oxidative species (ROS). This underlines the role played by the core nanorods as plasmonic light harvesters in the NIR range and constitutes the first example of a NIR-activated enzyme-like catalyst.
 
Article of reference:

Ortega-Liebana MC,  Hueso JL,  Arenalcd R,  Santamaria J. Titania-coated gold nanorods with expanded photocatalytic response. Enzyme-like glucose oxidation under near-infrared illumination. Nanoscale, 2017, 9,5, 1787-1792

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Jesús Izco, Coordinator of NANBIOSIS, leading the Health Innovation Group at the MATERPLAT Steering Committee Meeting

MATERPLAT, the Spanish Technological Platform of Advanced Materials and Nanomaterials, emerged in 2008 as framework for meetings and collaborations between the different agents of the National Enterprise, Science and Technology System interested in promoting the research, development and application of advanced materials and nanomaterials.

On February 3, 2017 the leaders of the MATERPLAT Innovation Groups met to define the lines of action of the working groups during the year 2017. These groups are transportation, health, energy, raw materials, and cities Intelligent.

They were present, following the order of the photograph: Back row, from left to right: Luis Guaita (KERABEN), José Manuel Puente (ARCELORMITTAL), Marta Serrano (CIEMAT), Eduardo Troche (IMDEA MATERIALS), José Manuel Baena (REGEMAT3D), Rafael Domínguez (AIRBUS). Front row, from left to right: Emilio Nieto (CEINNMAT), Nerea Anacabe (TECNALIA), Jesus Izco (NANBIOSIS-CIBERBBN), Miguel Angel Rodiel (IMDEA MATERIALS), Jose Sánchez (AIRBUS), Carlos Mendoza (AIRBUS) and Alfonso Grande (REPSOL) (AIRBUS, REPSOL, AIMPLAS, KERABEN, CEINNMAT, ITC, CIEMAT, ARCELORMITTAL, CIBER-BBN, REGEMAT3D, TECNALIA and IMDEA MATERIALS). The meeting took place in Getafe (Madrid) in the seat of AIRBUS, entity that holds the presidency of MATERPLAT.

In the meeting the participants agreed as the main action of the Innovation Groups, the preparation of a document entitled “Technological Strategy of Advanced Materials and Nanomaterials – MATERPLAT”, which serves as a reference in the coming years to identify priorities and opportunities for R & D + i in the field of advanced materials and nanomaterials.

MATERPLAT Steering Committee
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3DBio-impression systems and bio-ink for the regeneration of cartilage and bone

The Nanobiocel Group, coordinator of Unit 10 of NANBIOSIS participate in a public-private collaborative project to reach clinical application in the regeneration of osteochondral lesions, which mainly affect the knee and ankle joints.

The new project is funded by the Challenges-Collaboration program of the Ministry of Economy, Industry and Competitiveness. It has a budget of 691,000 euros for 3 years and the participation of two Spanish companies (Bioibérica and REGEMAT3D), the Higher Council for Scientific Research (CSIC), the University of Granada, the Center for Biomedical Research in Network Bioengineering, Biomaterials and Nanomedicine (CIBER -BBN) and its ICTS NANBIOSIS.

The companies and research groups participating in this project will work in the manufacture of three-dimensional mesh pieces or scaffolding designed with 3D bio-printing systems. These pieces will be fed with cells that make it possible to generate tissues in vitro to regenerate lesions. The ultimate goal is the development of new bio-inks (in which meshes and cells are combined) that are implanted in bone and cartilage.

In addition, the high prevalence of joint injuries makes them very interesting as the first application of bio-printing, with a view to its use in clinical practice”, Explains Patricia Gálvez, director of the Advanced Therapies Unit of Bioibérica, the coordinating company of this project.

A worldwide pioneering project

The company REGEMAT3D has developed a system of devices for bio-pioneering worldwide. This system, intended for research groups in its initial version, allows bio-printing three-dimensional meshes loaded with various cell types (chondrocytes and mesenchymal stem cells) for the regeneration of cartilage. This type of fabric has a number of advantages compared to others because of its relative simplicity, and above all because it is not necessary that a previous cultivation has been carried out.

From the scientific point of view, there are several improvements to be made in the area of ​​3D bio-printing to make this technology so promising can be used in the clinic with guarantees of success. It is necessary to develop new biomaterials for meshes that mimic biological materials with similar mechanical and chemical properties. These biomaterials have to be printable and their parameters have to be controllable. It is also necessary to access a well characterized and reproducible source of cells to feed these pieces that can be obtained in large quantities to be able to repair wide areas of tissue.

For this task, they have joined forces REGEMAT3D, Bioibérica, the Nanobiocel Group of CIBER-BBN, coordinator of Unit 10 of NANBIOSIS, the research group CTS-205 of the Department of Pharmacy and Pharmaceutical Technology and the research group CTS-963 of Advanced Therapies: Differentiation, Regeneration and Cancer, both belonging to the University of Granada and the Biomaterials Group of the Polymer Science and Technology Institute of CSIC, also belonging to CIBER-BBN.

All these companies and research groups contribute with their know how in bio-printing to the development of pharmaceutical products for the treatment of joint injuries, cellular therapies and biomaterials, in a way that constitutes a multidisciplinary consortium with wide guarantees of success.

Nanbiosis - New bioadhesive with 3D printing technique to improve pterygium surgeryLogo FEDER - Nanbiosis

“Promover el desarrollo tecnológico, la innovación y la investigación de calidad”

bioprinted human cells
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Equations that can save thousands of lives

Esther Pueyo, from the research group BSICoS, coordinator of Unit 27 of NANBIOSIS, explains for the program “En route with science” of Aragon Television, her research on arrhythmias: irregularities in the functioning of the heart. Arrhythmias are the cause of 25,000 deaths per year and half of hospital admissions in Spain.

First of all they study experimentally (extracting tissues from the heart of animals and humans) how the electrical activity of the said tissues is. Then, the information collected is introduced in mathematical models to understand the heart and to make predictions of what can happen in the future and why some behaviours in the heartbeat of a patient can be dangerous. For that process, stochastic equations are used that do not have a single solution and adapt to the variability of biology. These equations allow researchers to better interpret what the electrocardiogram signals say and to make predictions of risk with greater reliability. This is a multidisciplinary research in which mathematicians, engineers, physicists, biologists, electrophysiologists collaborate to make the most of the data obtained from patients.

To carry out this research, Esther Pueyo heads the European project “MODELAGE” for which she obtained a “Starting Gran” with funding of 1.5 million euros. They model patient data collected for the project to obtain different models, not only for each individual, but also for the different tissues or cells of the same patient.

In this project they study the aging of the heart, but in the BSICoS group, they also study other types of arrhythmias, such as heart attack, ischemia, or heart behaviour of astronauts participating in a special mission, who are at increased risk for arrhythmias or babies with congenital diseases that provide them with an increased risk of having arrhythmias.

Computational modelling necessary to reproduce the experimental and clinical observations and the signal analysis are be developed using the computing platform, Unit 27 of NANBIOSIS.

For further information:

http://alacarta.aragontelevision.es/programas/en-ruta-con-la-ciencia/  Cap 44

Equations that can save thousands of lives
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A multiplexing nanophotonic biosensor for cancer diagnosis

The group Biosensors and bio-analytic applications, led by Laura Lechuga,​ coordinator of Unit 4 of NANBIOSIS, has developed a methodology through a nano-photonic sensor (known as bimodal waveguide interferometer) capable of quantifying, directly and mark-free, the different messenger RNA isoforms generated by alternative splicing.

The expertise in biodeposition and biodetection systems of Lechuga’s group has permitted a thorough analytical study and optimization of the methodology, achieving not only total selectivity, but also excellent levels of sensitivity and reproducibility, and obtaining the lowest levels of detection in direct detection of messenger RNA isoforms generated by this mechanism without the need for PCR amplification (polymerase chain reaction).

The results of the study have recently been published in Scientific Reports (of the Nature group) and show a new methodology for the analysis of alternative splicing processes in a fast, simple and direct way, overcoming the main problems of conventional techniques. In addition, it opens the possibility of developing more efficient tools for the diagnosis and monitoring of therapy, providing a more informative, specific and precise analysis.

Article of reference:

Analysis of alternative splicing events for cancer diagnosis using a multiplexing nanophotonic biosensor. Scientific Reports 7, Article number: 41368 (2017) doi:10.1038/srep41368.

A multiplexing nanophotonic biosensor for cancer diagnosis
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STAFF III database published at Physionet

The  STAFF III database have  gone public at Physionet! https://physionet.org/physiobank/database/staffiii/

The STAFF III database was acquired during 1995–96 at Charleston Area Medical Center (WV, USA) where single prolonged balloon inflation had been introduced to achieve optimal results of percutaneous transluminal coronary angiography (PTCA) procedures, replacing the typical series of brief inflations. The lead investigator Dr. Stafford Warren designed the study protocol together with Dr. Galen Wagner at Duke University Medical Center (Durham, NC, USA); Dr. Michael Ringborn (Blekinge Hospital, Karlskrona, Sweden) was responsible for data acquisition. The database consists of ECG recordings from 104 patients, accounting for substantial inter-patient variability in reaction to prolonged balloon inflation as well as variability of heart rhythm and waveform morphology. Only patients receiving elective PTCA in one of the major coronary arteries were included. Patients suffering from ventricular tachycardia, undergoing an emergency procedure, or demonstrating signal loss during acquisition, were excluded.

Since its acquisition, the STAFF III Database has been distributed by Prof. Leif Sörnmo (Lund University, Sweden), responsible for the acquisition equipment and software. The use of the STAFF III database has broadened considerably over the years, with importance for several other research problems than high-frequency ECG analysis. Although the original study protocol of the database was designed to address a set of clinical issues, the database has turned out to be highly valuable also for developing, improving, and evaluating a wide range of signal processing techniques. This database has prompted methodological development in many areas related to ischemia, see the review by Laguna and Sörnmo (2014), were the use of high performance computing platforms as NANBIOSYS are used for the analysis.

The database was prepared for PhysioNet by:

STAFF III database published at Physionet
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MRSI-based generation of nosological images for noninvasive therapy response assessment in preclinical GBM

Nuria Arias Ramos from GABRMN-UAB, research group coordinator of Unit 25 of NANBIOSIS, presented on January 30th, an oral communication at the youngSMIN | young Spanish Molecular Imaging Network Meeting.

The title of the communication is “Multi slice MRSI-based generation of nosological images for noninvasive therapy response assessment in preclinical GBM”, written by Nuria Arias-Ramos, SilviaLope-Piedrafita, Victor Mocioiu, Margarida Julià-Sapé, Carles Arús and Ana Paula Candiota.

The work is basically centered in extending the preliminary GABRMN study based on MRSI  acquired in a preclinical glioblastoma (GB), both under treatment and control, with pattern recognition and source extraction for noninvasive therapy response assessment. The preliminary study was  performed in a single tumoral slice, but the GB is a well-known heterogeneous tumor and also presents heterogenous response to treatment, so the multislice acquisition was an important step in order to characterize therapy response assessment as a whole, not centered in a single slice. Tumors were stratified in no response, partial response and high response after calculating the percentage of the ‘responding’ part of the tumor, and histopathological studies for correlation are in progress.

The MRSI acquisition and processing steps were performed in NANBIOSIS facility U25.

MRSI-based generation of nosological images for noninvasive therapy response assessment in preclinical GBM
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