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Posts on Jan 1970

A Study of Fluid Dynamics and Chemical Parameters

Researchers of NANBIOSIS -ICTS U9, Synthesis of Nanoparticles Unit, from CIBER-BBN andAragon Institute of Nanoscience (INA), have published an interesting study on the Scientific Jounal Materials of Fluid Dynamics  and  Chemical Parameters.

The objective of the the work was to produce gastroresistant Eudragit (R) RS100 nanoparticles by a reproducible synthesis approach that ensured mono-disperse nanoparticles under the size of 100 nm. Batch and micromixing nanoprecipitation approaches were selected to produce the demanded nanoparticles, identifying the critical parameters affecting the synthesis process. To shed some light on the formulation of the targeted nanoparticles, the effects of particle size and homogeneity of fluid dynamics, and physicochemical parameters such as polymer concentration, type of solvent, ratio of solvent to antisolvent, and total flow rate were studied. The physicochemical characteristics of resulting nanoparticles were studied applying dynamic light scattering (DLS) particle size analysis and electron microscopy imaging. Nanoparticles produced using a micromixer demonstrated a narrower and more homogenous distribution than the ones obtained under similar conditions in conventional batch reactors. Besides, fluid dynamics ensured that the best mixing conditions were achieved at the highest flow rate. It was concluded that nucleation and growth events must also be considered to avoid uncontrolled nanoparticle growth and evolution at the collection vial. Further, rifampicin-encapsulated nanoparticles were prepared using both approaches, demonstrating that the micromixing-assisted approach provided an excellent control of the particle size and polydispersity index. Not only the micromixing-assisted nanoprecipitation promoted a remarkable control in the nanoparticle formulation, but also it enhanced drug encapsulation efficiency and loading, as well as productivity. To the best of our knowledge, this was the very first time that drug-loaded Eudragit (R) RS100 nanoparticles (NPs) were produced in a continuous fashion under 100 nm (16.5 +/- 4.3 nm) using microreactor technology. Furthermore, we performed a detailed analysis of the influence of various fluid dynamics and physicochemical parameters on the size and uniformity of the resulting nanoparticles.

According to these findings, the proposed methodology can be a useful approach to synthesize a myriad of nanoparticles of alternative polymers.

Article of reference: DOI 10.3390/ma13132925

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Innovation Radar “Great EU-funded Innovations”

The Innovation Radar Platform is a European Commission initiative to identify high potential innovations and innovators in EU-funded research and innovation framework programmes based on their market readiness.

Researchers of NANBIOSIS U8 Micro– Nano Technology Unit, led by Rosa Villa, contribute to the @InnoRadarEU with two innovations related to their research on graphene-based neuroprobes:

Flexible neural probes for monitoring infraslow brain activity


Multiplexed Neurosensor Arrays based on GrapheneFETs and MOS2

This innovation was developed under the Horizon 2020 project BrainCom to generate a High-density cortical implants for cognitive neuroscience and rehabilitation of speech using brain-computer interfaces.

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II Conference on Nanotoxicity, organised by Nanomed Spain, NANBIOSIS and Materplat, Sept. 22

NANBIOSIS is organizing an on-line Conference on Nanotoxicity in collaboration with Nanomed Spain and Materplat, next September 22, to debate about the efect of nanotoxicity of nanoparticles and nanotechnologies in health.

Nanotechnology, a science involved in the design, production, and use of structures and objects that have at least one of their dimensions on the scale of 100 nanometers or less, is enabling progress to be made in various areas with far-reaching repercussions. scope for society. Currently, there are several areas in which nanotechnology is under development or even in the practical application phase.

However, manufactured nanoparticles can have very different properties and effects than those of the same materials in conventional sizes, which can pose new risks to human and other species’ health. Some nanoparticles, which are used as a vehicle for the drugs to reach the desired cells in greater quantity, to reduce the side effects of the drug in other organs or for both, have the same dimensions as certain biological molecules and can interact with them.

The increase in potential health risks has created a new discipline, nanotoxicity, that is, the study of toxicity produced by the effect of nanoparticles and nanomaterials. The objective of this conference, co-organized by the advanced materials and nanomaterials platform (MATERPLAT), NANBIOSIS ICTS and the nanomedicine platform (Nanomed Spain), is to learn more about the lines that are being followed in research in the area of ​​nanotoxicity, the progress of different projects in this field, as well as existing tools to understand and reduce the toxicity of nanoparticles and nanomaterials.

The event will count with the expertise of Marisa Gonzalez, Scientific Director of NANBIOSIS U16 Surface Characterization and Calorimetry Unit, speaking about Surface characterization of micro and nanoplastics among other experts.

The assistance is free but it is necessary to register. For further information, agenda and registration click here 

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Workshops on Robotic Surgery with experimental models at CCMIJU

This year, CCMIJU, partner of NANBIOSIS, at Cáceres, has organised some new hands-on and customised workshops with robotic technology, expected for 2020 last term.

Specifically CCMIJU is organising, in collaboration with the Enterprise ABEX-Excelencia Robótica SL, some workshops on Robotic Surgery (da Vinci Xi) using experimental models. They are addressed to health professionals from several specialties (urology, gynaecology, general surgery and thoracic surgery) interested in practising with this technology.

The workshops will count on a clinical specialist from ABEX, who will explain the technical features of the robotic equipment, the associated technologies and the virtual simulator for exercises. Subsequently the health professionals, monitored by a tutor-specialist, will be able to practice a surgical approach on the virtual simulator and in vivo, on experimental models.

The mentioned workshops will be developed in a full day, morning- afternoon, in two sessions: virtual simulation an in vivo model. Both of them will be customised and will count on a tutor for surgical training in experimental models.

The focus is to improve the patients’ health care, training surgeons and health professionals in innovative solutions.

For further info, please e-mail  idoiadiaz@ccmijesususon.com

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The Scientific Director of NANBIOSIS Unit 7, awarded with the Narcís Monturiol medal for his contribution to science and technology

The Catalan Government announced yesterday the Narcís Monturiol Medal award for scientific and technological merit to the Director of NANBIOSIS Unit 7 Nanotechnology Unit from CIBER-BBN and IBEC, Josep Samitier Martí, for his contribution to the development of the Catalan system of science and technology.

The Narcís Monturiol Prize was established by the Generalitat of Catalonia in 1982, in honor of the Catalan scientist and inventor Narciso Monturiol, to award the people and entities that have made an outstanding contribution to the scientific and technological progress of Catalonia.

It is awarded in the form of medals and plaques. The medals are awarded to individuals, and the plates to legal entities.

This year, ten researchers from the Catalan knowledge system have received this distinction (Ramon Brugada and Terradellas, Paul Christou, M. Teresa Espinal and Farré, Manel Esteller, Pilar García Almirall, Paloma Mas, Victoria Reyes García, Jordi Salas-Salvadó, Josep Samitier and Martí and Sebastián Xambó Descamps), also the Institute of Photonic Sciences (ICFO) has received the Narcís Monturiol Plate, which recognizes an institution of the country.

For further information here

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Unlocking the brain with novel graphene technology

Researchers of NANBIOSIS U8 Micro– Nano Technology Unit of CIBER-BBN at the Barcelona Institute of Microelectronics have participated in the recent developments of a new graphene-based detection platform that could be the gateway to unlock superior understanding of the brain by providing a measure of high brain activity resolution and in real time. This research has been developed within the framework of the EU BrainCom project.

The European Union’s Horizon 2020 research project, BrainCom, is coordinated by the ICN2 Advanced Electronic Materials and Devices Group led by Professor José A. Garrido and the CIBER BBN GBIO Group and the Nanbiosis U8 platform participate. (Anton Guimera, Xavier Illa, Ana Moya, Elisabet Prats and Rosa Villa)

Arguably, a better understanding of the working principles of the human brain remains one of the major scientific challenges of our time. Despite significant advances made in the field of neurotechnology in recent years, neural sensing interfaces still fall short of equally meeting requirements on biocompatibility, sensitivity, and high spatio-temporal resolution. The European Union Horizon 2020 research project BrainCom, coordinated by the ICN2 Advanced Electronic Materials and Devices Group led by ICREA Prof. José A. Garrido, is tackling these problems. BrainCom brings together experts from the fields of neurotechnology, neuroscience, and ethics to develop novel technologies capable of overcoming these limitations and shed light onto the mechanisms of information encoding and processing in the brain.

In four research articles published between March and April 2020 — featured in Elsevier’s Carbon, IOP’s 2D Materials, Wiley’s Small, and American Chemical Society’s Nano Letters — researchers from the BrainCom consortium present the technological advances achieved in the project, discuss in-depth methodology, and demonstrate novel capabilities for high resolution sensing of the brain’s electrical activity. The recent developments exploit the unique properties of graphene, an atom-thick layer of carbon, which conforms with the soft and convoluted surface of the brain providing an excellent neural sensing interface. Graphene sensors have an additional advantage that represents a turning point in neural engineering: the sensing mechanism of these graphene active sensors (so-called transistors) is compatible with  electronic multiplexing, a technology that enables transmitting the signals detected by multiple sensors through a single micrometric wire. This implies that the number of sensors on the neural implants can be increased while minimizing the footprint of the connectors required to link the implants to external electronic equipment.

This technology, developed in close collaboration with Dr Anton Guimerà at the CSIC Institute of Microelectronics of Barcelona (IMB-CNM, CSIC), has been evaluated in pre-clinical studies at the laboratory of neuroscientist Prof. Anton Sirota at Ludwig-Maximilians Universität (LMU, Munich). A collaborative and multidisciplinary approach is crucial for the success of the project, which aims at addressing a very hard scientific and technological challenge. The human brain has an astonishing complexity, consisting out of as many as 100 billion neurons. To fully understand the underlying principles of such a convoluted system requires the simultaneous detection of the electrical activity of large neural populations with a high spatial and temporal resolution. Unfortunately, current neural sensing technologies present a trade-off between spatial resolution and large-area coverage of the brain surface. The work carried out by the BrainCom project’s researchers shows how graphene-based sensors represent an outstanding building block for such large scale and highly sensitive neural interfaces. As explained in the recently published papers, graphene sensors can be reduced in size to the dimension of about one single neuron, while maintaining a high signal quality. In addition, their sensitivity expands over a wide range of frequencies; from infra-slow oscillations to very fast signals elicited by individual cells.

These findings clear the path for a scale-up of graphene sensor technology towards arrays with an ultra-high-count of sensors. Such biocompatible and high bandwidth neural interfaces can have a great impact on the development of neuroprosthesis, which enable a direct communication between the brain and a computer. These results represent the fruition of long-term EU research initiatives, which pursue the ambitious goal of restoring speech to impaired patients by reading the signals in their brains, which are related to their intentional speech. The research consortium will now focus on upscaling the production of these neural interfaces and testing their performance in safe human clinical trials. This and other applications of graphene sensors are also supported by the EU Graphene Flagship within the Biomedical Technologies work package.

Reference Articles:

Garcia-Cortadella R, Schaefer N, Cisneros-Fernández J, Re L, Illa X, Moya-Lara A ,Santiago S, Guirado G, Villa R, Sirota A, Serra-Graells F, Garrido JA, Guimerà-Brunet A Switchless Multiplexing of Graphene Active Sensor Arrays for Brain Mapping Nano Letters (2020) DOI: 10.1021/acs.nanolett.0c00467

Garcia-Cortadella R, Masvidal-Codina E, de la Cruz J, Schaefer N, Schwesig G, Jeschke C, Martínez-Aguilar J, Sánchez-Vives MV, Villa R, Illa X, Sirota A, Guimerà-Brunet A, Garrido JA Distortion‐Free Sensing of Neural Activity Using Graphene Transistors Small (2020) 1906640, March 2020. DOI: 10.1002/smll.201906640

Schaefer N, Garcia-Cortadella R, Martínez-Aguilar J, Schwesig G, Illa X, Moya Lara A, Santiago S, Hébert C, Guirado G, Villa R, Sirota A, Guimerà-Brunet A, Garrido JA Multiplexed Neural Sensor Array of Graphene Solution-Gated Field-Effect Transistors 2D Materials 7(2), 2020. DOI: 10.1088/2053-1583/ab7976

Schaefer N, Garcia-Cortadella R, Bonaccini Calia A, Mavredakis N, Illa X, Masvidal-Codina E, de la Cruz J, del Corro E, Rodríguez L, Prats-Alfonso E, Bousquet J, Martínez-Aguilar J, Pérez-Marín AP, Hébert C, Villa R, Jiménez D, Guimerà-Brunet A, Garrido JA Improved metal-graphene contacts for low-noise, high-density microtransistor arrays for neural sensing Carbon 161, 647-655, 2020. DOI: 10.1016/j.carbon.2020.01.066

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Biocidal releasing dressings of natural origin to treat topical wounds and avoid antibiotic resistance

Researchers of NANBIOSIS U9 Synthesis of Nanoparticles Unit, of the CIBER-BBN at the University of Zaragoza, use thymol as a natural biocide, a component present in the essential oils of thyme and oregano, thus fighting against the predictions that in 2050 there will be more deaths from infections associated with antibiotic-resistant bacteria than from cancer.

Some topical wounds caused by burns, by surgical procedures, diabetic foot ulcers, fistulas, pressure ulcers, etc. they can become infected and become chronic, rendering current treatments ineffective. Currently, the devitalized tissue is removed, the area is cleaned, it is drained and depending on the microbial presence present (fungi and / or bacteria) a topical antimicrobial treatment is used. However, in many cases it is inefficient, in addition the use of antibiotics favors the potential development of resistance

Researchers of the NFP group of the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) belonging to the University Institute in Nanoscience of Aragon (INA) of the University of Zaragoza, which coordinates unit 9 of NANBIOSIS, have developed biocide-releasing dressings of origin natural to avoid bacterial resistance to antibiotics.
Specifically, thymol has been used as a natural biocide, which is a component present in the essential oils of thyme and oregano. Said dressings have been validated in bacterial cultures and also in animal experiments showing that they are capable of reducing bacterial infections without harming skin cells (fibroblasts and keratinocytes).

Reducing bacterial load without damaging adjacent tissue

The team of researchers, led by Silvia Irusta and Manuel Arruebo, together with Gracia Mendoza (currently at the Instituto de Investigación Sanitaria de Aragón (IIS Aragón), in collaboration with the Lluís Luján group of the Veterinary School, deliberately infected a wound topical created in the animal model with Staphylococcus aureus, a common pathogen in cutaneous bacterial infections and in infections associated with implants.On these wounds, the biocidal release dressings of natural origin were applied and it was possible to reduce the bacterial load present without showing signs of irritation. or inflammation in adjacent tissue. Following this line of research, in a subsequent study (ACS Applied Bio Materials 2020, 3, 5, 3430–3439), the same team demonstrated that these dressings show less local toxicity than even one of the most commonly used local antiseptics, bactericides and fungicides, chlorhexidine.

The doses required to eliminate the infection using biocides of natural origin are greater than the equivalent doses of antibiotics, however, given the tremendous concern about antibiotic resistance, this proposal may be a future alternative. These results, which have been published in the European Journal of Pharmaceutics and Biopharmaceutics, will undoubtedly help to counteract the forecasts issued by the Centers for Disease Control and Prevention of the United States, which predict that in 2050 more people will die from infections associated with antibiotic-resistant bacteria than from cancer. Therefore, any validated solution that can replace antibiotics without generating resistance can overcome some of their limitations. In the future, the task force will seek to increase the effectiveness of these naturally occurring biocides by combining them with other antiseptics.

Reference article:

Drug-eluting wound dressings having sustained release of antimicrobial compounds Enrique Gámez-Herrera, Sara García-Salinas, Sofía Salido, María Sancho-Albero, Vanesa Andreu, Marta Pérez, Lluís Luján, Silvia Irusta, Manuel Arruebo, Gracia Mendoza. Eur J Pharm Biopharm. DOI: 10.1016/j.ejpb.2020.05.025

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Cardiac hypertrophy research with NANBIOSIS unit 17 Confocal Microscopy Service participation

A new article has been recently published about Cardiac hypertrophy research in the Scientific Reports Jorunal by NatureResarch, counting with the expertise of NANBIOSIS unit 17 Confocal Microscopy Service form CIBER-BBN and University of Alcalá de Henares.

Cardiac hypertrophy is the abnormal enlargement, or thickening, of the heart muscle, resulting from increases in cardiomyocyte size and changes in other heart muscle components, such as extracellular matrix. This article relates more especifically with the link between long term exposure to xenoestrogen Bisphenol-A and adverse cardiovascular effects and the role of necroptosis in cardiac response to BPA had not yet been explored.

NANBIOSIS U17, Confocal microscopy Unit is mentioned in the Materials and Methods section: Slides containing tissue sections were incubated with the primary antibodies overnight 4 °C. After washing with PBS, the slides were incubated with FITC, Alexa-488, or Alexa-647-conjugated secondary antibodies for 1 hour at room temperature. Nuclei were stained with Hoechst. Images were taken for data quantification using a Leica TCS SP5 confocal microscope (UAH-NANBIOSIS-CIBER-BNN). At least five different fields per condition were obtained.

In the picture, F) Representative confocal images from heart sections of CT and 8 weeks treated BPA mice after injection with Evans blue (red fluorescence) followed by immunostaining for α-SMA (green). Nuclei were labeled with Hoechst in blue (n = 4 mice per condition). (a and b) CT hearts sections obtained at different magnifications showed no signs of EB extravasation. (c) and (d) are different sections of coronary arteries of BPA hearts with extravasation areas. Scale bar = 25 μm (a and c) and 50μm (b and d). IL = intraluminal area and (*) marks areas of EB extravasation.

Article of refrence:

Reventun, P., Sanchez-Esteban, S., Cook, A. et al. Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway. Sci Rep 10, 4190 (2020). https://doi.org/10.1038/s41598-020-61014-1

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A new nanoconjugate blocks acute myeloid leukemia tumor cells without harming healthy ones

Researchers from NANBIOSIS U18 Nanotoxicology Unit at the Institut d’Investigació Biomèdica de Sant Pau (IIB Sant Pau) and NANBIOSIS U1 Protein Production Platform (PPP) at the Universitat Autònoma de Barcelona (UAB) toghether with researchers of Institut de Recerca contra la Leucèmia Josep Carreras (IJC) have demonstrated the efficacy of a new nanoconjugate, designed in house, that blocks dissemination of leukemic cells in animal models of acute myeloid leukemia. These results have been published in a high impact scientific journal in the field of oncology and hematology, Journal of Hematology and Oncology. Most of the experimental work has been performed in the nanotoxicology and protein production ICTS “NANBIOSIS” platforms from CIBER-BBN.

NANBIOSIS U1 PPP has advised and helped the researchers in the production of recombinant proteins, which has allowed to successfully explore the capacity of proteins from the human microbiome, that is, from bacteria and their bacteriogages, to generate, through genetic engineering, biocompatible nanomaterials and Non-immunogenic for potential use in human clinics, such as vehicles for drug delivery or regenerative medicine.

Acute myeloid leukemia (AML) is a heterogeneous disease which usual treatment is very aggressive and produces severe side effects to the patients. In order to reduce these adverse effects, the researchers have developed a nanomedicine that is specifically targeted to the tumor cells without damaging normal cells. This new protein nanoparticle is bound to a toxin, named Auristatin, which is between 10 and 100 times more potent than the drugs typically used in the clinic. In particular, this nanoconjugate is targeted only to the cells that express in their membrane a receptor called CXCR4, which is overexpressed in leukemic cells. Thus, this nanoparticle can only enter and deliver the toxin into the cells that express this receptor. It should be noted that CXCR4 is overexpressed in a large proportion of leukemic cells in patients with poor prognostic or refractory disease, so it could have a major clinical impact on these AML patients.

The researcher team led by Ramon Mangues, from IIB Sant Pau, Antonio Villaverde and Esther Vázquez, from UAB, all members of CIBER-BBN, has demonstrated that the nanoconjugate is able to internalize in the leukemic cells through the CXCR4 receptor and kill them. In addition, they have demonstrated the capacity of this nanoparticle to block dissemination of leukemic cells in a mouse model producing without any kind of associated toxicity or adverse effects. Thanks to its targeting to leukemic cells it could help AML patients that cannot be treated with current drugs because of their high toxicity, such as this experienced by elderly patients or patients with other non-favorable characteristics that exclude conventional treatment. Furthermore, the novel nanoparticle could be used to treat patients that have developed resistance to drugs or those that have experienced relapse, since their leukemic cells would likely have high expression of the CXCR4 receptor. Hence, there is a wide range of patients that could benefit of this new treatment, which could have  a major clinical impact if its effectiveness was confirmed in further clinical trials.

It is worth pointing out that the CXCR4 receptor is overexpressed in more than 20 different cancer types, which expression associates with poor prognosis. Therefore, this nanodrug could be evaluated in the near future as a possible treatment in other tumor types of high prevalence.

The intellectual property of this nanomedicine has been licensed to the SME biotech Nanoligent, which aim is continuing the so far successful access to public and private funds to complete the preclinical development to enter clinical trials in acute myeloid leukemia, before being tested in other cancer types.

Article of reference:

An Auristatin Nanoconjugate Targeting CXCR4+ Leukemic Cells Blocks Acute Myeloid Leukemia Dissemination. Victor Pallarès, Ugutz Unzueta, Aïda Falgàs, Laura Sánchez-García, Naroa Serna, Alberto Gallardo, Gordon A Morris, Lorena Alba-Castellón, Patricia Álamo, Jorge Sierra, Antonio Villaverde, Esther Vázquez, Isolda Casanova, Ramon Mangues. DOI: 10.1186/s13045-020-00863-9

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From natural by-products to cell delivery systems for regenerative medicine

Researchers from NANBIOSIS U10 Drug Formulation unit (CIBERBBN – UPV/EHU led Rosa María Hernández, have developed a biomedical device consisting of by-products from the food industry and which displays excellent properties for use in regenerative medicine. The work has been published in the Green Chemistry Jurnal, one of the most prestigious international journals in chemistry and the second most important one in the field of sustainable science. The work has also been selected for the cover page of this issue.

Researchers in the UPV/EHU’s NanoBioCel and Biomat groups have developed a biomedical device consisting of by-products from the food industry and which displays excellent properties for use in regenerative medicine. The novel device comprises soy protein and chitin, which form a matrix with a porous, interconnected microarchitecture similar to that of certain body tissues.

Added to the growing need in recent years to develop new therapies for biomedical applications is the widely called-for social requirement to be environmentally friendly. In this respect, the group of researchers has shown that natural by-products from the food industry, normally discarded in industrial processes, could be an excellent source of biomaterials for producing biomedical devices.

“It is important to point out that to date no one has exploited the potential in regenerative medicine displayed by soy protein and chitin blended in a microporous matrix,” stressed the researchers. “As the first milestone in this respect, this novel device incorporates two natural components obtained from the food industry, thus contributing towards the widely called-for social requirement to upgrade waste from production on an industrial level. The device has also displayed some physico-chemical and mechanical properties suitable for applications in regenerative medicine. What is more, it has also been found to be totally biocompatible not only in in vitro cell lines but also in an in vivo murine model.  Finally, we have confirmed that this device is capable of hosting a large number of viable stem cells inside it, thus increasing its level of bioactive compound secretion and displaying its potential as a very effective vehicle in cell therapy.”

This biotechnological approach may have a potentially successful application in the matrix-based regenerative medicine industry. These devices capable of hosting stem cells are destined to be the revolution, not only in biomedical research but also in everyday clinical practice. “Clinical scenarios as complex as chronic injuries or bone problems need a multifocal approach which combines bioactive matrices with biological agents having regenerative effects,” they concluded.

Article of reference

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