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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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II Course on introcuction to research and laboratory techniques in biomedicine

JUMISC has organised the Course on introcuction to research and laboratory techniques in biomedicine which wil take place during the month of July, co-Directed by Francisco M. Sanchez Margallo, Deputy Scientific Director of NANBIOSIS  and Javier García Casado, Scientific Director of NANBIOSIS unit 14 Cell Therapy.

Further information and programe: here

Inscriptions: here

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Manuel Doblaré, researcher of NANBIOSIS U13, new Chairman of IMDEA Materials Foundation

Manuel Doblaré researcher of the Group Applied Mechanics and Bioengineering – AMB and NANBIOSIS U13 Tissue & Scaffold Characterization Unit of CIBER-BBN and I3A presides, from this month, the Board of Trustees of the Imdea Materiales Foundation.

The IMDEA Materials Institute, one of the seven Madrid Institutes for Advanced Studies (IMDEA), is a public research centre founded in 2007 by Madrid’s regional government. The goal of the Institute is to do research at the forefront of Material Science and Engineering, attracting talent from all around the globe, and collaborating with companies in an effort to transfer fundamental and applied knowledge into valuable technology

In an interview by I3A-UZ Manuel Doblaré highlights from IMDEA its great evolution and major strategic lines, with projects lasting three or four years and the balance he has achieved between very powerful basic research and strong collaboration with the industry.

Manuel Doblaré was the founder of the I3A and the forst scientific director of the CIBER-BBN. Today, in addition to chairing the IMDEA Materials Foundation, he is a Fellow of the European Alliance for Engineering and Biomedicine (EAMBES) and the World Biomechanics Council, as well as the director of the Gadea Ciencia Foundation, whose objective is to promote the improvement and advancement of science, technology and innovation in Spain.

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NANBIOSIS scientists in Aragón, explain on TV their research againts coronavirus

The special program on the coronavirus pandemic  by “En Ruta con la Ciencia” of Aragón Televisión, analyzes different aspects of the disease with special attention to the work of Aragonese scientists. Among them, two  research groups that coordinate NANBIOSIS units 9 and 27.

Starting at minute 44’45 ‘of the program, Doctor Jesús Lázaro, researcher of the BSICoS group of I3A-UZ and CIBER-BBN, led by Pablo Laguna, which coordinates NANBIOSIS U27 High Performance Computing Unit, explains his research. For almost 3 years, Jesús Lázaro had been working on a European project to develop a respiratory and heart rate monitoring system for patients with EPOC to control and predict episodes of worsening disease, but the current situation has led him to redirect his goal to try to provide solutions in this crisis and have creates an application for the mobile phone to detect from our home, if we have a viral infection: – “The parameters measured by this application have to do with the nervous system Autonomous, – explains Jesús Lázaro – they are the heart rate, its variability and the respiratory rate, these three parameters would allow observing a response through SARS-COV-2. The application works based on a technology that uses the flash of the mobile phone camera as a receiver to obtain a signal that is proportional to the blood volume of the finger put on the flash light, what allows detecting both, the number of beats per minute and the morphology of the arterial pulse, to obtain the respiratory rate. At the moment this application has been tested by the research staff and the next phase is to assess it with the general public. As the application is based on detecting autonomic markers, a very high sensitivity is expected, as well as a very low specificity, which would allow detecting not only SARS-COV-2 but analyzing these parameters in other contexts and in other diseases, even detecting other eventual viruses of other eventual pandemics ”.

Further information on the research project here

Starting at 28’14 ’’ One of the problems of the coronavirus test is what is known as false negatives, people who have passed the disease, but are not detected and could continue to spread it. A research group is developing early diagnostic tests to try to reduce this error rate. Pilar Martín Duque, at the IACS Aragonese Institute of Health Sciences, is a researcher of the NFP group of the INA and the CIBER-BBN, led by Jesús Santamaría, which coordinates NANBIOSIS U9 Synthesis of Nanoparticles Unit : – “All techniques have a detection limit and a sensitivity, it is necessary to have a minimum amount of virus in the body for the virus being detected, if the viral load is low it may not be detected at that time, it is possible that some patients with a low viral load recover, but in other cases the virus begins to grow and after two weeks they can be positives”- explains Pilar Martín. Her project makes PCRs more effective by concentrating the viral load before testing. – “There is a curious case, – continues Pilar -, of an American navy ship, moored in China, in which five sailors were detected to be infected by coronavirus, so they were quarantined during fourteen days and, after new tests with negative results, they were allowed to return to the United States on the ship. However halfway through the journey, the same five sailors suffered an outbreak of the disease. Therefore, our study would be useful for detecting patients with the virus tested for the first time or for not discharging patients who had been already diagnosed if they really are not yet negative”.  It is estimated that 10% of the population has infected 80%, these 10% are the so-called “superspreaders”, they are infected with a high viral load, but they feel well and do not know about it. For example, there have been several cases in choirs, such as the Choir of Zarzuela in Madrid, where 53 members were contagious out of the 80 members form the choir, this is because when singing or speaking very loudly, more drops are produced that carry the virus”. But why do some people become infected before others? Pilar explains that this is related to some, already known, receptors for entry of viruses, the AC2 receptors, and there are people who has more of these receptors than others.

Further information on the research here:

If we have learned anything from this pandemic it is the importance of health and research, a robust research system has the knowledge, tools, and human talent to respond to any situation. If we want to be prepared for the next pandemic, it is important and essential to continue betting on research.

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Optimization of Recycled-Membrane Biofilm Reactor as a sustainable biological treatment for microcystins removal with nanbiosis expertise.

Jesús Morón-López (IMDEA), Serena Molina (Chemical Engineering Department, University of Alcalá) have recently published the results of their research about Recycled-Membrane Biofilm Reactor as a sustainable biological treatment for microcystins (MC) removal. The study addresses the lack of sustainable technologies for water treatment, while opening an alternative in sustainable solid waste management under a circular economy approach.

The biofilm visualization has been performed by ICTS “NANBIOSIS”, more specifically by the Unit 17 Confocal Microscopy Service of Ciber in Bioengineering, Biomaterials & Nanomedicine (CIBER-BNN) at the Alcala University (CAI Medicine Biology) led by Juan Manuel Bellón y Gemma Pascual. In this case, the biofilm attached to the recycled membrane was observed under the confocal laser scanning microscope (CLSM Leica SP5, Leica Microsystems) of NANBIOSIS Unit 17.

Article of refrence:

Jesús Morón-López, Serena Molina, Optimization of Recycled-Membrane Biofilm Reactor (R-MBfR) as a sustainable biological treatment for microcystins removal Biochemical Engineering Journal 153 (2020) 107422

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The European Commission releases a video showing the European project against coronavirus led by prof Laura Lechuga

The European Commission Representation in Barcelona has published the five-minute video “The EU fights the Covid-19 from Catalonia” in which four researchers explain the projects they are working on.

The researchers appearing in the video are  Laura Lechuga Scientific Director of NANBIOSIS unit 4 from CIBER-BBN and ICN2-CSIC and Group Leader of CIBER-BBN at the ICN2 Nanobiosensors and Bioanalytical Applications Group), who works on a sensor to detect the coronavirus in a faster, easier and cheaper way than with current PCRs, Núria Montserrat (IBEC), who works on micro-kidneys made from stem cells to test a drug able to block the virus, Alfonso Valencia (BSC), who explains the huge computation power that the BSC can bring into play to find already existent drugs that may be suitable to treat Covid-19,  and Gabriel Anzaladi (Eurecat), who studies the presence of the virus in wastewater to estimate the people infected in a given zone or the probability of a new outbreak.

The European Commission is present in all Member States through a network of offices, called “representations”, which aim to report on the Commission’s activity and to bring the policies of the European Union closer to citizens. They are also in charge of capturing the social reality and the climate of opinion at street level and transferring this information to the European institutions in Brussels so that their policies better respond to the needs of citizens. In Catalonia and the Balearic Islands, this work is carried out by the “Representation of the European Commission in Barcelona”.

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Hydrogels structured with dual stimuli responsive for biomedical applications

Researchers of NANBIOSIS Unit 17 Confocal Microscopy Service have participated in the research carried out structuring hydrophobic domains in Poly(N-isopropylacrylamide-co-Methacrylic acid) hydrogels for biomedical aplplications.

Hydrogels are cross-linked polymeric networks, which have the ability to hold a large amount of water in their structure. Hydrogels can be designed to respond to a specific stimulus such as temperature, pH, ionic strength, light, etc., making making them suitable for biomedical applications, as drug delivery.

The most popular responsive polymeric hydrogel is made of poly(N-isopropylacrylamide) (PNIPAM). The copolymerization of NIPAM with an acrylic/methacrylic acid monomer permits the development of a hydrogel with a dual stimuli response: temperature and medium pH. Additionally, the acid groups can electrostatically interact with positively charged drugs, the interaction being sensitive to pH. Therefore, these hydrogel systems have great potential for drug delivery applications.

At it seemed that the structuring of dual stimuli responsive hydrogels had not been reported, the authors deat with the structuring of poly(N-isopropylacrylamide-co-methacrylic acid) hydrogels to create hydrophobic domains by means of copolymerization of NIPAM with methacrylic acid and a small percentage of a nitrocatechol monomer in an aqueous medium that contained SDS. This structured hydrogel allows is capable of loading hydrophobic molecules as well as charged drugs. The hydrogel permitted cell adhesion and growth as well as its detachment when the temperature fell below the LCST.

As reported in the article, fluorescence images of cells were obtained with a laser scanning confocal microscope (LSCM) (Leica TCS-SP5) through the Confocal Microscopy Service of ICTS ‘NANBIOSIS’ U17 of the Biomedical Research Networking Centre on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN at the University of Alcalá, Madrid, Spain).
equipped with a Diode 405 nm and a continuous Ar ion laser (488, 514,
561 and 633 nm).

Article of refrence:

Structuring hydrophobic domains in Poly(N-isopropylacrylamide-co-
Methacrylic acid) hydrogels. Mar López-González, M. Melia Rodrigo, Mercedes Valiente, Isabel Trabado, Francisco Mendicutib, Gema Marcelo. European Polymer Journal. April 2020 https://doi.org/10.1016/j.eurpolymj.2020.109695

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