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CIBER-BBN: A New Car Brand?

You might think CIBER-BBN sounds like a car brand. And in fact, just like in the automotive world, engineers and scientists from multiple fields at CIBER-BBN are designing new diagnostic techniques and therapies tailored to the needs of the patients.

But what do those initials mean?

Designing and manufacturing a car requires the integration of many disciplines, all working in unison and in collaboration. In some areas of biomedicine, things work in a very similar way. CIBER stands for the Biomedical Research Networking Center (in Spanish, Centro de Investigación Biomédica en Red), created by the Instituto de Salud Carlos III (ISCIII). It is a scientific-technical support body for the Spanish healthcare system, and for society at large. So when we talk about “CIBER,” we’re referring to a public scientific consortium made up of a vast national network of more than 500 research and clinical groups, distributed across over 100 different institutions. This enormous structure is subdivided into 13 different research areas, each dedicated to a specific field of biomedical research.

And BBN is one of those areas.

Multiple Disciplines in One Area

CIBER-BBN stands for Bioengineering, Biomaterials and Nanomedicine. That makes it one of the most eclectic and multidisciplinary areas within CIBER. Let’s explore what each part means, explained by three prestigious researchers working in CIBER-BBN.

Bioengineering and Medical Imaging

Much like designing a car body, bioengineering involves creating comfortable and functional designs, except in this case, it’s for cells to feel at ease while performing their functions, growing faster, or aiding in tissue regeneration. Also, it’s hard to find a car these days without sensors telling us what’s going on. Likewise, bioengineering helps us analyze the images and signals our body emits, so we can detect, decode, and map what the eye cannot see.

“Through bioengineering, we’e designing sensors that capture signals produced by the body, whether electrical, optical, or chemical.”

—Dr. Olga Conde

“Through bioengineering, we’re designing sensors that capture signals produced by the body, whether electrical, optical, or chemical,” explains Dr. Olga Conde, Associate Professor at the University of Cantabria and a CIBER-BBN member since 2016. “These sensors must be small enough to be placed inside the body in a portable way, enabling continuous monitoring of chronic diseases and aging. Interpreting the large volume of signals and analyzing all this information is complex, so we develop computing systems, mostly based on Artificial Intelligence, that help clinical staff in decision-making. We also work on improving diagnostic techniques through automated analysis of medical images. This include new imaging techniques that allow better planning and real-time monitoring of interventions. For instance, we can now outline tumors in real time before removing them. This leads to improved recovery rates and more efficient use of resources.”

Biomaterials and Advanced Therapies

Like in the case of a car, the human body at some point may need parts repaired or replaced to function optimally. That’s where biomaterials and advanced therapies come into play, acting as spare parts for the body, designed to extend its life and improve component efficiency, promoting safer and longer-lasting performance.

“Biomaterials and advanced therapies are revolutionizing regenerative medicine“

—Dr. Selma Benito

“Biomaterials and advanced therapies are revolutionizing regenerative medicine,“ says Dr. Selma Benito, postdoctoral researcher at CIBER-BBN. She is working in tissue repair, regeneration, and wound healing within Dr. Pascual’s group at the University of Alcalá. She is also the Scientific Coordinator of NANBIOSIS Unit 17. “Biomaterials offer new ways to repair weakened tissues, such as abdominal wall defects. These are commonly known as hernias.” Dr. Benito explains that biomaterials act like “scaffolds or reinforcements” that support healing of weakened or torn tissues. Some of them are even equipped with antibacterial properties or are designed to be reabsorbed by the body, reducing postoperative risks. “Advanced therapies also promote regeneration of damaged tissues, speeding up the healing of hard-to-treat wounds like chronic ulcers or diabetic and pressure sores, while reducing inflammation and risk of infection.” These strategies not only improve the quality of life of the patients, but also help optimize healthcare system resources.

Nanomedicine

No matter how comfortable, stylish, safe, or customizable a car is, its main job is to get us where we want to go. That’s where the third branch of CIBER-BBN comes in: nanomedicine. This field focuses on designing nanoscale “vehicles” that deliver drugs to their precise destinations, wrap them to prevent early activation, and release them at just the right time. This way, we can control where our vehicle goes and when it acts.

“Though there’s still much to discover, nanomedicine is paving the way for a new era in fighting diseases like cancer”

—Dr. Eugenia Mato

“Though there’s still much to discover, nanomedicine is paving the way for a new era in fighting diseases like cancer,” says Dr. Eugenia Mato, a CIBER researcher affiliated with the Research Institute of Sant Pau Hospital in Barcelona and Associate Professor at the University of Barcelona. “One key to its success is nanoparticles: tiny biomaterials that can deliver drugs or genes directly into damaged cells in our tissues.” She gives a compelling example: “In cases of aggressive thyroid cancer, these advances, combined with better tumor understanding, are opening the door to more effective and personalized treatments. These approaches are likely to improve both patient quality of life and survival rates in the coming years.”

Beyond the Lab: The Medicine of the Future

Aside from having a well-designed car, who wouldn’t want a GPS to guide them efficiently to a cure? Just as a car needs a driver to reach its destination, CIBER-BBN aims to bring its research to real solutions for patients. The road is long and requires many steps and extensive knowledge. That’s why CIBER-BBN, alongside other institutions, created NANBIOSIS: a platform that offers services for doctors, researchers, and companies to tackle challenges they can’t address alone.

Biological chassis, nano-vehicles for drug delivery, safety, and personalization. For CIBER-BBN, the car… is you.

Credits
Eugenia Mato
Olga M. Conde
Selma Benito
Gabriel Alfranca

This article is part of a practical activity from the CIBER Communication Course, whose next edition will be held in May 2025 in Madrid.

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Happy Day of Chemistry! The role of Chemistry in a sustainable research in health

Today, November 15 is a day of celebration for us, the Day of the Chemistry in Spain!

Chemistry is the science that studies matter, how it is composed, its properties and how its structures are transformed and, as matter is everything, including living beings and ourselves, we can say that chemistry is omnipresent and transversal in all areas surrounding us. Chemistry is everywhere, we ourselves are chemistry and our health and our life is chemistry.

“Everything around us is chemistry in the environment, foods, what we use and what we touch every day. Our own body is a sophisticated complex factory with an infinite number of chemical processes taking place on a perfect and synchronized manner”- points Pilar Marco, Scientific Director of NANBIOSIS U2 Custom Antibody Service (CAbS) from CIBER-BBN at IQAC-CSIC.

The crucial role of chemistry in everyday life is also evidence in the development of current technology and the economy. According the VCI Prognos Study, the Global growth forecast for Industrial Sectors, places the chemical industry in the fist position. As far as national picture, the INE Statistics on R+D Activities 2020 -last publish report-, chemical and pharmaceutical industry employs the 22,2 % of research staff recruited and the investment and expenditure on the chemical and pharmaceutical industry represents the 23,6% R+D and Innovation -above the motor vehicles industry.

Thanks to chemical and pharmaceutical research,

medicines, vaccines and health products have made great strides in fighting diseases and improving quality of life. Thanks to chemical and pharmaceutical medicine research, in few years, it will be possible, for example, to count on smart implants delivering personalised drugs only where cancer or infections are detected or biosensors circulating in our body to find diseases only one week after infection.

At the Institute of Advanced Chemistry of Catalonia, four NANBIOSIS units of CIBER-BBN use chemistry to deliver new therapeutic and diagnostic approaches that improve the quality of life of the society.

One of the research lines of the Nb4D group-U2 CabS at IQAC-CSIC (led by Pilar Marco and Nuria Pascual) focuses on the chemical signals that bacteria emit to communicate with each other and thus develop virulence mechanisms. Their knowledge will allow the development of new therapeutic and diagnostic strategies to mitigate the serious problem of antimicrobial resistance.

NANBIOSIS U3 Synthesis of Peptides Unit– MS4N group, led by Miriam Royo, explores the use of diverse types of chemical multivalent platforms (oligomers, dendrimers, polymers, micelles and lipid nanovesicles) for the development of drug delivery systems for cancer treatment, protein delivery systems for the treatment of lysosomal diseases and macromolecular compounds that have intrinsically therapeutic properties with application to central nervous system diseases.

Chemistry plays an essential role in helping society achieve Sustainable Development Goals (SDGs)

In 2015 the United Nations created a universal call to action to end poverty, protect the planet, and ensure that all people enjoy peace and prosperity by 2030. This framework, comprising 17 aspirational goals known as the Sustainable Development Goals (SDGs)

Chemistry is key to achieve the SDG 3: Good Health & Well-Being with the development of new technologies that will provide a deeper understaunding of human health, making posible better, cheeper and faster medical diagnosis and treatmens.

In this sense, Carlos Rodriguez Abreu, Scientific Director of NANBIOSIS Unit for the characterization of nanostructured liquids (U12) explains: “The goals of sustainable development are producing a shift towards surfactants not based on petroleum derivatives, but derived from other raw materials that are more biocompatible and that allow a circular economy that is less aggressive with the environment. Quality control is necessary with regard to the properties of the products that contain surfactants, such as the droplet size in emulsions, the particle size in suspensions, their colloidal stability over time, among others. Additionally, products must be precisely formulated to optimize the use of raw materials and obtain the desired properties. In this context, the NANBIOSIS U12, acredited with ISO 9001:2015 by AENOR, offers a wide range of advanced analysis techniques for the determination of different colloidal properties such as droplet size and particle size, colloidal stability, viscosity, surface tension, pore size distribution, and determination of phase behavior and structure for the tailor-made formulation of surfactant and colloid systems for pharmaceutical and biomedical applications.

The Nucleic Acid Chemistry group at IQAC-CSIC – NANBIOSIS U29 Oligonucleotide Synthesis Platform (OSP) is developing new compounds based in DNA and RNA to detect and treat diseases participating in several projects with several research and industrial partners such as La Marato de TV3 (Covid), Oligofastx, Caminan2, Osteoatx. These new drugs use the natural mechanisms for gene regulation to treat undruggable diseases such Muscular dystrophy and others. Importantly special attention is made to design novel synthetic protocols to produce less organic waste what contributes to the sustainable development. 

We wish to all the family of chemistry professionals new projects and inspiration to achive humans Good Health & Well-Being and keep the world moving!

And Happy Chemistry Day, too, for all the chemistry enthusiasts!

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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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Why the poor biodistribution so far reached by tumor-targeted medicines?

Cell-selective targeting is expected to enhance effectiveness and minimize side effects of cytotoxic agents. Functionalization of drugs or drug nanoconjugates with specific cell ligands allows receptor-mediated selective cell delivery. However, it is unclear whether the incorporation of an efficient ligand into a drug vehicle is sufficient to ensure proper biodistribution upon systemic administration, and also at which extent biophysical properties of the vehicle may contribute to the accumulation in target tissues during active targeting. To approach this issue, structural robustness of self-assembling, protein-only nanoparticles targeted to the tumoral marker CXCR4 is compromised by reducing the number of histidine residues (from six to five) in a histidine-based architectonic tag. Thus, the structure of the resulting nanoparticles, but not of building blocks, is weakened. Upon intravenous injection in animal models of human CXCR4+ colorectal cancer, the administered material loses the ability to accumulate in tumor tissue, where it is only transiently found. It instead deposits in kidney and liver. Therefore, precise cell-targeted delivery requires not only the incorporation of a proper ligand that promotes receptor-mediated internalization, but also, unexpectedly, its maintenance of a stable multimeric nanostructure that ensures high ligand exposure and long residence time in tumor tissue.

Protein production has been partially performed by the  ICTS NANBIOSIS U1, Protein Production Platform and the nanoparticle size analysis by the U6  of NANBIOSIS Biomaterial Processing and Nanostructuring Unit. Biodistribution studies were performed by the U18 of the ICTS NANBIOSIS, Nanotoxicology Unit.

The concept presented by the authors of the present research might represent a convincing explanation of the poor biodistribution so far reached by tumor-targeted medicines, including antibody-drug conjugates. In addition to this, they offer a potential developmental roadmap for the improvement of these drugs, of high intrinsic therapeutic potential, to reach satisfactory efficiencies in the clinical context.

Hèctor López-Laguna, Rita Sala, Julieta M. Sánchez, Patricia Álamo, Ugutz Unzueta, Alejandro Sánchez-Chardi, Naroa Serna, Laura Sánchez-García, Eric Voltà-Durán, Ramón Mangues, Antonio Villaverde and Esther Vázquez. Nanostructure Empowers Active Tumor Targeting in Ligand-Based Molecular Delivery. Part. Part. Syst. Charact. 2019.

DOI: 10.1002/ppsc.201900304

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Release of targeted protein nanoparticles from functional bacterial amyloids: A death star-like approach

Sustained release of drug delivery systems (DDS) has the capacity to increase cancer treatment efficiency in terms of drug dosage reduction and subsequent decrease of deleterious side effects. In this regard, many biomaterials are being investigated but none offers morphometric and functional plasticity and versatility comparable to protein-based nanoparticles (pNPs). Researchers of NANBIOSIS units 1 and 18 are co-authors of an article  publish by Journal of Controlled Release in which it is described a new DDS by which pNPs are fabricated as bacterial inclusion bodies (IB), that can be easily isolated, subcutaneously injected and used as reservoirs for the sustained release of targeted pNPs. Our approach combines the high performance of pNP, regarding specific cell targeting and biodistribution with the IB supramolecular organization, stability and cost effectiveness. This renders a platform able to provide a sustained source of CXCR4-targeted pNPs that selectively accumulate in tumor cells in a CXCR4+ colorectal cancer xenograft model. In addition, the proposed system could be potentially adapted to any other protein construct offering a plethora of possible new therapeutic applications in nanomedicine.

In the study the researchers have generated novel smart biomaterials gathering most of the desirable features for implantable DDS, with cost effectiveness and simplicity in the biofabrication process. In this regard, single step fabricated IBs when injected subcutaneously rendered a long lasting release of targeted pNPs, able to enter to the blood stream and specifically target the tumor for as long as 10 days and they have described for the first time an approach for the fabrication of protein DDS based on protein deposition as IBs and their sustained release in form of fully functional targeted pNPs. This technology provides and stable source of targeted protein nanoparticles during long periods within the body with the action at distal points from the implantation site and pave the way for the appearance of new more efficient and less invasive treatments for a broad number of pathologies.

Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the U1. Protein Production Platform (PPP), whereas the in vivo biodistribution assays were performed in the NANBIOSIS U18. Nanotoxicology Unit,

For further information see https://sciencedirect.com/science/article/pii/S0168365918301780?via%3Dihub

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