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New spin off of VHIR “BSURE Medical” led by Simó Schwartz (NANBIOSIS U20)

Dr. Simó Schwartz, Scientific Director of NANBIOSIS U20 and head of the “Drug Delivery and Targeting group” of CIBER-BBN and VHIR, toghether with Dr. Jaume Alijotas (VHIR), have promoted the creation of the Spin-off ·BSURE Medical· for the devlopment of products and services for the diagnosis, prevention and consultation of aspects related to treatments with all types of bioimplants.

One of the objectives of the Drug Delivery and Targeting group is to carry out preclinical studies to determine the effects and toxicities of drug delivery systems, cell therapies and biomaterials. Studies chace been carried out through the Nanbiosis unit U20, of which the CIBBIM-Nanomedicine platform for functional validation and preclinical studies (FVPR) is a part. The group’s interest in studying the immune-related adverse effects caused by different biomaterials, allowed the identification and validation in two clinical studies of the predictive use of specific genetic biomarkers associated with severe late responses caused by injectable biomaterials, the basis of the new company BSure Medical.

Dr. Jaume Alijotas and Simó Shwartz have led the development of a procedure that makes it possible to determine, reliably and easily the risk of suffering serious late-onset immune, local, regional or systemic adverse effects (edema, angioedema, induration of skin, multiple inflammatory nodules, panniculitis, even granulomatous or autoimmune diseases…) after implantation of an injectable biomaterial, such as dermal or subcutaneous fillers. This risk is strongly associated with the presence of certain antigen profiles in a biological sample of the individual, which allows them to be easily identified from the analysis of blood or saliva samples.

The technology is patented and has been validated in two independent clinical trials coordinated by the Systemic Autoimmune Diseases Unit of the Vall d’Hebron University Hospital in Barcelona and by the Dermatology Department of the Erasmus Medical Center, Rotterdam and the Department of Plastic Surgery, VU University Medical Center, Amsterdam. The VHIR has granted BSURE a license to use and exploit it exclusively and worldwide. The patent has already been granted in Europe, Brazil and Japan

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Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation

Researchers of NANBIOSIS U12. Nanostructured liquid characterization unit from CIBER-BBN and IQAC-CSIC have recently published an article entitled Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation in the scientific journal Food Hydrocolloids

The research which results are published involves the encapsulation of drops of water-in-water emulsions, which could be used as vehicles for the administration of active principles.

Characterization of emulsions and capsules was performed in the Unit 12 of NANBIOSIS Nanostructured Liquid Characterization Unit.

Water-in-Water (W/W) emulsions were prepared in aqueous mixtures of an anionic polyelectrolyte (sodium alginate, NaAlg), with a globular protein (bovine serum albumin, BSA). This combination showed phase separation at two different intervals of pH, and their phase behavior was studied. BSA-in-alginate emulsions were obtained and dropped into Ca2+, Fe3+ or chitosan solutions, forming capsules with diameters around 2–4 mm, by ionic complexation of sodium alginate, located in the continuous phase of the emulsions. The results showed a strong dependence on the cation or polycation. Capsules prepared with Ca2+ were not robust and collapsed during freeze-drying, while Fe3+ induced the gelation of the interior of capsules, even at short (5 min) contact time. Better results were obtained when encapsulating with chitosan and applying longer immersion times. In these capsules, the liquid interior contained well-preserved BSA-in-alginate emulsions droplets, identical to the initial emulsions before encapsulating. Freeze-dried spherical capsules prepared with alginate/Fe3+ or alginate/ chitosan shells had smooth surfaces, and a highly porous interior, templated by the presence of W/W emulsion droplets.

Article:

M. Michaux, N. Salinas, J. Miras, S. Vílchez, C. González-Azón, J. Esquena,
Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation, Food Hydrocolloids, Volume 113, 2021, 106406,

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Smart-4-Fabry final workshop

Next Wedneday, February 3, 2021 will take place the on-line event Smart-4-Fabry Final Workshop.  

Smart-4-Fabry is a european project, coordinated by CIBER-BBN wich has been developed during four years. This project is a sign of cooperation at European level to boost nanomedicine development and translation to clinical stages.

This project is also a clear example of the relevance of access to advanced research infrastructures as NANBIOSIS -ICTS. Four NANBIOSIS units have collaborated and contributed to Smart-4-Fabry development:

“The Fabry disease (FD) is a lysosomal storage disorder (LSD) that currently lacks an effective treatment” as Prof. Nora Ventosa, IP of the project, explained for NANBIOSIS blog – The aim of Smart-4-Fabry is to obtain a new nanoformulation of GLA, that will improve the efficacy and toleration compared to the actual treatment with non-formulated GLA.

In the final workshop experts will talk about how, why and for what the solution proposed by Smart4Fabry was conceived.

Registrations and program at https://smart4fabry.cientifis.com/

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New Center for Research in Advanced Pharmaceutical Development

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

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

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

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

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Electrocardiogram-Derived Tidal Volume During Treadmill Stress Test

Researchers of BSICoS Group and NANBIOSIS ICTS U27 High Performance Computing from CIBER-BBN and I3A-UZ have published a new article in the scientific journal IEEE Transactions Biomedical Engineering. proposing a new method to estimate tidal volume during stress test based only on the electrocardiogram signal.

Electrocardiogram (ECG) has been regarded as a source of respiratory information with the main focus in the estimation of the respiratory rate. Although little research concerning the estimation of tidal volume (TV) has been conducted, there are several ECG-derived features that have been related with TV in the literature, such as ECG-derived respiration, heart rate variability or respiratory rate.

In this work, resarchers exploited these features for estimating TV using a linear model. 25 young (33.4 ± 5.2 years) healthy male volunteers were recruited for performing a maximal (MaxT) and a submaximal (SubT) treadmill stress test, which were conducted in different days. Both tests were automatically segmented in stages attending to the heart rate. Afterwards, a subject-specific TV model was calibrated for each stage, employing features from MaxT, and the model was later used for estimating the TV in SubT.

During exercise, the different proposed approaches led to relative fitting errors lower than 14% in most of the cases and than 6% in some of them. Low achieved fitting errors suggest that TV can be estimated from ECG during a treadmill stress test. The results suggest that it is possible to estimate TV during exercise using only ECG-derived features.

Article of reference:

Milagro, J; Hernando, D; Lázaro, J; Casajús, J A; Garatachea, N; Gil, E; Bailón, R. Electrocardiogram-Derived Tidal Volume During Treadmill Stress Test
IEEE Transactions Biomedical Engineering, 67 (1), 2020. DOI: 10.1109/TBME.2019.2911351

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Hybridization of men and machines, with Rosa Villa

Prof. Rosa Villa, Scientific Director of NANBIOSIS U8 Micro– Nano Technology Unit, and group leader of the research group of biomedical applications of ICNM–CSIC and CIBER-BBN, has participated in the program of National Radio of Spain “The Open Future: Biobots” led by Tato Puerto.

Following the recent presentation by a team of American scientists of the design of “reprogrammable organisms”, halfway between a robot and a living being, that is, an extraordinary living machine made from frog cells, the program of National Radio of Spain called “Open Future” has dedicated a session to explain what are “Biobots” and to generate debate and reflexion with experts like Prof, Rosa Villa.

Asked about the current outlook and futute of the “Hybridization of men and machines“, Rosa Villa has explained that in the area of ​​micro and nanotechnology, (where her group works), the hybridization takes place to make neural interfaces, to interrelate with the human brain registering many more signals from the brain and being able to offer patients greater mobility for artificial prosthetics or even other human enhancement activities. The main problem for this at a technological level is that a series of biological and material processes have to be carried out while these processes need to be easilly integrated by the human body. The functioning of the brain is still very unknown, the brain is a very closed box, very well protected and inaccessible but the amount of signals that are registered is spectacular. The latest technologies and materials, such as graphene, make it possible to build sensors with smaller electrodes that allow many signal points to be recorded in the brain at the same time, with a signal quality that was not possible to reach until now which allows scientists to know a series of high and low frequency signals that give very useful information from the brain, not only to know how it works, but also to predict diseases such as epilepsy or Alzheimer’s.

The program can be listen here, in Spanish

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Nucleic Acids Chemistry, new book release by Ramon Eritja

Ramón Eritja, Scientific Director of NANBIOSIS Unit 29 Oligonucleotide Synthesis Platform (OSP) has just published a new book “Nucleic Acids Chemistry, modifications and conjugates for Biomedicine and Nanotechnology“, Anna Avinó, Scientific Coordinator of NANBIOSIS Unit 29 is also a writer of the book.

The book “Nucleic Acids Chemistry” takes the most important aspects of the methodology of oligonucleotides synthesis, that is currently expanding by the endorsement of a dozen of new medicines, such as the first medicine based on interfering RNA for the control of LDL and cholesterol in blood that will facilitate the decrease of cardiovascular illnesses.

The writing of the book has been directed by Dr. Ramon Eritja, of Centro de Investigación en Red de Nanomedicina (CIBER-BBN) and is Research Professor at Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), being its director between 2012-2017. The co-authors are Carme Fàbrega, Anna Aviñó, Santiago Grijalvo, Andreia F. Jorge, from IQAC-CSIC, Carlos González from Instituto de Química Física Rocasolano (IQFR-CSIC) and Raimundo Gargallo from University de Barcelona  The book began to be written in mid-2019, although most of the book was written during the lockdown.

In the last five years, an expansion of technologies based on DNA and RNA in diagnosis and therapeutic use has been produced, and it has been very important in the research of quick solutions to avoid the COVID pandemic and, predictably, the research group’s environment has led the development of several solutions, like biosensors for the direct detection of SARS-CoV-2.

A former PhD student of Ramon Eritja group, Dr. Ramón Güimil García, Head of Synthetic Oligonucleotides bei BioNTech, has participated in the development of the BioNTech-Pfizer mRNA vaccine. Another doctor, Brendan Manning, formed member of the group, has participated in the development of a diagnosis kit named Sherlock, which uses the CRISPR-Caspasa system for the detection of the virus that causes COVID.

Dr Erija completed his doctoral thesis at the University of Barcelona directed by Dr. Ernest Giralt on the subject of peptide synthesis. In 1984 he carried out his first postdoc with Dr. Itakura at the Beckman Research Institute of City of Hope in Los Angeles where the production of the first synthetic genes was carried out, highlighting the production of synthetic insulin that, with the name of humulin, solved the problems generated from the use of swine insulin. In 1986 she completed the second postdoc with Dr. Caruthers at the University of Colorado at Boulder. In this laboratory, phosphoramidites were developed, which are the reagents used today for the production of synthetic DNA and RNA. Upon his return to Barcelona, ​​he joined the CSIC Research and Development Center where he organized the first research group in our country focused on oligonucleotide synthesis. In 1984 he moved to the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany) to direct for 5 years one of the most prestigious groups in DNA and RNA Chemistry in Europe. Upon his return to Barcelona, ​​he was part of the Barcelona Institute for Biomedical Research (IRB Barcelona) and was recognized as a group of excellence by the CIBER-BBN. In 2012 he moved to the IQAC-CSIC to occupy the direction of the institute until 2017.

Refernce:

Nucleic Acids Chemistry – Modifications and Conjugates for Biomedicine and Nanotechnology Edited by: Ramon Eritja. De Gruyter | 2021 DOI: https://doi.org/10.1515/9783110639537

The book can be purchased here: link

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New patented peptide to allows the faster internalization of drugs within cells and the design of more effective therapeutic nanoconjugates

Researchers of NANBIOSIS Unit 20 In vivo Experimental Platform of CIBER-BBN and Vall d’Hebron Research Institute (VHIR) have patented a peptide that, in comparison to the current standard treatment, is much faster, internalizes much more, and does not cause any toxicity.

The membrane of a cell is an effective barrier that hinders the targeted delivery of molecules, such as therapeutic compounds. During the last years, several strategies have been developed to get the molecules into the cell interior but, in general, the methods developed still show a low efficacy and / or toxicity. “The use of therapeutic nanoconjugates such as nanomedicines facilitates the transport and delivery of drugs in target cells, but often with less efficiency than we would like,” says Dr Simó Schwart Jr, head of the Scientific Director of NANBIOSIS Unit 20 and the CIBBIM-Nanomedicine group: Direction i Alliberament Farmacològic del Vall d’Hebron Research Institute (VHIR)/CIBER-BBN.

Given the need to get more drugs or proteins into cells, one of the alternatives to be able to increase the amount that enters their interior more quickly is what is known as Cell penetrating peptides or cellular internalizing peptides, small sequences of amino acids that have the ability to interact with the plasma membranes of cells and, as a result of this interaction, make it easier to internalize the cargo they carry. An example of application would be when an internalizing peptide binds to a therapeutic nanoconjugate, achieving a greater capacity for the nanoconjugate to enter the cell interior and, therefore, to release the drugs it carries into the cells.

Until now, one of the most important internalizing peptides used has been known as TAT. Now, a team of researchers led by Dr. Schwartz Jr, has discovered a sequence common to a family of peptides that significantly outperforms the TAT results and facilitates the cellular internalization of nanoconjugates in a very significant way. These peptides are derived from a membrane protein called CD300 which has a very high capacity to interact with sphingomyelin, a lipid found in all plasma membranes and also in intracellular organelles. “The peptides in our patent”, explains Dr. Simó Schwartz Jr, “are derived from an extracellular part of CD300, which has a high capacity to bind sphingomyelin. Compared to the current standard treatment, TAT, CD300f7 is much faster, internalizes much more, and does not cause any toxicity. The use of these peptides in nanomedicine therefore facilitates and increases the internalization process of all the cargo they carry. This means that we are able to introduce drugs into cells in less time and in greater quantities ”. The results of this discovery not only allow for faster internalization within the cell, but also open the door to designing much more effective therapeutic nanoconjugates.

Souce of information: VHIR news

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Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity

Researchers of Nanbiosis U8 Micro– Nano Technology Unit, from CIBER-BBN and IMB-CNM-CSCIC have published an article in Nature Communications on Graphene arrays for long-term and wireless mapping of epicortical brain activity. A collaborative work in the framework of the Brain Com and Graphene EU projects. The article mentions the participation of NANBIOSIS-ICTS.

Graphene active sensors have demonstrated promising capabilities for the detection of electrophysiological signals in the brain. Their functional properties, together with their flexibility as well as their expected stability and biocompatibility have raised them as a promising building block for large-scale sensing neural interfaces. However, in order to provide reliable tools for neuroscience and biomedical engineering applications, the maturity of this technology must be thoroughly studied. Here, we evaluate the performance of 64-channel graphene sensor arrays in terms of homogeneity, sensitivity and stability using a wireless, quasi-commercial headstage and demonstrate the biocompatibility of epicortical graphene chronic implants. Furthermore, to illustrate the potential of the technology to detect cortical signals from infra-slow to high-gamma frequency bands, we perform proof-of-concept long-term wireless recording in a freely behaving rodent. Our work demonstrates the maturity of the graphene-based technology, which represents a promising candidate for chronic, wide frequency band neural sensing interfaces.

Article:

Garcia-Cortadella, R., Schwesig, G., Jeschke, C. et al. Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity. Nat Commun 12, 211 (2021). https://www.nature.com/articles/s41467-020-20546-w

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A rare genetic bone pathology is identified from massive sequencing methods

The Andalusian Center for Nanomedicine and Biotechnology (BIONAND) and the Center for Biomedical Research Network in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), both partners of NANBIOSIS, in collaboration with the International Registry of Skeletal Dysplasias of the University of California (Los Angeles) and Masaryk University, of the Czech Republic have described a new genetic disease of the skeleton using a precision medicine strategy.

This disease consists of extreme bone fragility with lack of mineralization and skeletal deformation associated with joint dislocation and heart disease, as well as a lung deficiency that causes perinatal lethality -at the time of birth-. Using massive sequencing methods – of all genes – researchers have identified the mutations that caused a type of rare bone pathology, specifically, those of the ‘LAMA5’ gene, responsible for encoding a cellular matrix protein that surrounds blood vessels in skeletal tissues.

“Our scientific team has spent years investigating rare genetic syndromes that affect the skeleton in order to provide a medical solution to patients with difficult diagnosis and treatment,” explains the researcher from the Department of Cell Biology, Iván Durán, lead author of this study, whose results have been published in the scientific journal ‘EBIOMEDICiNE’.

According to the expert, precision medicine is the key to discovering what genetic and molecular factors cause this type of pathology and, therefore, understanding the mechanism that causes them and being able to develop personalized therapies.

Thus, researchers have also described the disease mechanism by generating cellular models by gene editing, mimicking the mutations in ‘LAMA5’, with the aim of confirming whether these are the origin and knowing the molecular process that triggers the problem. These cellular models have been generated by genetic editing with CRISPR, introducing mutations that cause a null or hypomorphic gene.

“Thanks to these models, we discovered a new signaling pathway that governs the formation of the skeleton – so that the bone grows and remains healthy – which means that our work has not only led to the discovery of a new disease, but to a mechanism unprecedented that can be exploited for common bone disorders ” –explains Durán, “the presence of ‘LAMA5’ between cells that direct skeletal formation indicates, therefore, that the appearance of signals from special blood vessels can be a very effective weapon for bone repair and regeneration. Blood vessels not only provide irrigation to the bone, but also carry signals and house niches of stem cells that can be mobilized to induce a regenerative process. ‘LAMA5’ seems to be a key component for harboring pericyte-type stem cells”.

Article of reference:

Barad M, Csukasi F, Kunova-Bosakova M, Martin J, Zhang W, Taylor SP, Dix P, Lachman R, Zieba J, Bamshad M, Nickerson D, Chong JX, Cohn DH, Krejci P, Krakow D, Duran I. Mutations in LAMA5 disrupts a skeletal noncanonical focal adhesion pathway and produces a distinct bent bone dysplasia. 2020 EBioMedicine. Nov 23;62:103075. doi: 10.1016/j.ebiom.2020.103075

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