Novel Hydrogel-forming elastin-like recombinamers for biomedical applications

There is an increasing interest in developing advanced biomaterials with improved biocompatibility and functionality that might find uses in the field of biomedicine, for example in tissue engineering and regenerative medicine (TERM). Nowadays, recombinant polypeptides or polymers are one of the most prominent types of biomaterials, due to their nature. They are obtained through recombinant DNA technology, which allows the controlled biosynthesis of tailored polypeptides that may be designed to include combinations of polymeric amino acid sequences and/or bioactive domains. Within this type of biomaterials we can find elastin-like polypeptides (ELPs), which have also been recently termed elastin-like recombinamers (ELRs), according to their recombinant origin. These ELRs are composed of repetitions of the VPGXG (Val-Pro-Gly-X-Gly) pentapeptide, in which X (guest residue) can be any amino acid expect L-Proline. This composition confers the ELRs a smart behaviour of thermoresponsiveness defined by the so-called Inverse Temperature Transition (ITT) occurring above the Transition Temperature (Tt), which implies a phase transition of the dissolved ELR when this Tt is reached. Therefore, this thermal response is of great interest, since it has been shown to promote the formation of different structures, such as hydrogels that mimic the extracellular matrix, at the physiological temperature, whereas an ELR solution can be easily handled (e.g. injected in vivo) below the Tt. Furthermore, the Tt can be modulated depending on the polarity of the side chain of the amino acid chosen as guest residue. Moreover, if this residue contains functional goups, it can also be used for further chemical modifications in order to achieve, for instance, chemically (covalently) cross-linked hydrogels.Departamento de Bioquímica y Biología Molecular y FisiologíaDoctorado en Investigación Biomédic

Trends in the design and use of elastin-like recombinamers as biomaterials

Producción CientíficaElastin-like recombinamers (ELRs), which derive from one of the repetitive domains found in natural elastin, have been intensively studied in the last few years from several points of view. In this mini review, we discuss all the recent works related to the investigation of ELRs, starting with those that define these polypeptides as model intrinsically disordered proteins or regions (IDPs or IDRs) and its relevance for some biomedical applications. Furthermore, we summarize the current knowledge on the development of drug, vaccine and gene delivery systems based on ELRs, while also emphasizing the use of ELR-based hydrogels in tissue engineering and regenerative medicine (TERM). Finally, we show different studies that explore applications in other fields, and several examples that describe biomaterial blends in which ELRs have a key role. This review aims to give an overview of the recent advances regarding ELRs and to encourage further investigation of their properties and applications.Comisión Europea (project NMP-2014-646075)Ministerio de Economía, Industria y Competitividad (projects PCIN-2015-010 / MAT2016-78903-R / BES-2014-069763)Junta de Castilla y León (project VA317P18

Synthesis and characterization of a silk-elastin-like recombinamer fused to enhanced green fluorescent protein (SELR-EGFP) for the achievement of self-assembled fluorescent nanoparticles and physically cross-linked hydrogels

Se ha realizado el diseño, síntesis y caracterización de un recombinámero de tipo elastina fusionado a la proteína verde fluorescente, con la capacidad de formar distintas estructuras por auto-ensamblado en respuesta a la temperatura, desde nanopartículas a hidrogeles, con una aplicación potencial en el desarrollo de dispositivos biomédicos. Además, se han utilizado técnicas nanotecnológicas para el desarrollo de partículas fluorescentes con capacidad de adhesión e internalización celular.Departamento de Física de la Materia Condensada, Cristalografía y MineralogíaMáster en Nanociencia y Nanotecnología Molecula

Educational Warehouse: Modular, Private and Secure Cloudable Architecture System for Educational Data Storage, Analysis and Access

[Abstract] Data in the educational context are becoming increasingly important in decision-making and teaching-learning processes. Similar to the industrial context, educational institutions are adopting data-processing technologies at all levels. To achieve representative results, the processes of extraction, transformation and uploading of educational data should be ubiquitous because, without useful data, either internal or external, it is difficult to perform a proper analysis and to obtain unbiased educational results. It should be noted that the source and type of data are heterogeneous and that the analytical processes can be so diverse that it opens up a practical problem of management and access to the data generated. At the same time, ensuring the privacy, identity, confidentiality and security of students and their data is a “sine qua non” condition for complying with the legal issues involved while achieving the required ethical premises. This work proposes a modular and scalable data system architecture that solves the complexity of data management and access. On the one hand, it allows educational institutions to collect any data generated in both the teaching-learning and management processes. On the other hand, it will enable external access to this data under appropriate privacy and security conditions.Generalitat de Catalunya; 2017 SGR 93

FRET-Paired Hydrogel Forming Silk-Elastin-Like Recombinamers by Recombinant Conjugation of Fluorescent Proteins

Producción CientíficaIn the last decades, recombinant structural proteins have become very promising in addressing different issues such as the lack of traceability of biomedical devices or the design of more sensitive biosensors. Among them, we find elastin-like recombinamers (ELRs), which can be designed to self-assemble into diverse structures, such as hydrogels. Furthermore, they might be combined with other protein polymers, such as silk, to give silk-elastin-like recombinamers (SELRs), holding the properties of both proteins. In this work, due to their recombinant nature, we have fused two different fluorescent proteins (FPs), i.e., the green Aequorea coerulescens enhanced green fluorescent protein and the near-infrared eqFP650, to a SELR able to form irreversible hydrogels through physical cross-linking. These recombinamers showed an emission of fluorescence similar to the single FPs, and they were capable of forming hydrogels with different stiffness (G′ = 60–4000 Pa) by varying the concentration of the SELR-FPs. Moreover, the absorption spectrum of SELR-eqFP650 showed a peak greatly overlapping the emission spectrum of the SELR-Aequorea coerulescens enhanced green fluorescent protein. Hence, this enables Förster resonance energy transfer (FRET) upon the interaction between two SELR molecules, each one containing a different FP, due to the stacking of silk domains at any temperature and to the aggregation of elastin-like blocks above the transition temperature. This effect was studied by different methods, and a FRET efficiency of 0.06–0.2 was observed, depending on the technique used for its calculation. Therefore, innovative biological applications arise from the combination of SELRs with FPs, such as enhancing the traceability of hydrogels based on SELRs intended for tissue engineering, the development of biosensors, and the prediction of FRET efficiencies of novel FRET pairs.Este trabajo forma parte de Proyectos de Investigación financiados por la Comisión Europea (NMP-2014-646075, HEALTH-F4-2011-278557, PITN-GA-2012-317306 and MSCA-ITN-2014-642687), del MINECO (MAT2016-7R8903-R, MAT2016-79435-R, MAT2013-42473-R, MAT2013-41723- and MAT2012-38043), la Junta de Castilla y León (VA244U13 and VA313U14) y el Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León

Occurrence and ecological risks of pharmaceuticals in a Mediterranean river in Eastern Spain

Pharmaceuticals are biologically active molecules that may exert toxic effects to a wide range of aquatic organisms. They are considered contaminants of emerging concern due to their common presence in wastewaters and in the receiving surface waters, and the lack of specific regulations to monitor their environmental occurrence and risks. In this work, the environmental exposure and risks of pharmaceuticals have been studied in the Mijares River, Eastern Mediterranean coast (Spain). A total of 57 surface water samples from 19 sampling points were collected in three monitoring campaigns between June 2018 and February 2019. A list of 40 compounds was investigated using a quantitative target UHPLC-MS/MS method. In order to complement the data obtained, a wide-scope screening of pharmaceuticals and metabolites was also performed by UHPLC-HRMS. The ecological risks posed by the pharmaceutical mixtures were evaluated using species sensitivity distributions built with chronic toxicity data for aquatic organisms. In this study, up to 69 pharmaceuticals and 9 metabolites were identified, out of which 35 compounds were assessed using the quantitative method. The highest concentrations in water corresponded to acetaminophen, gabapentin, venlafaxine, valsartan, ciprofloxacin and diclofenac. The compounds that were found to exert the highest toxic pressure on the aquatic ecosystems were principally analgesic/anti-inflammatory drugs and antibiotics. These were: phenazone > azithromycin > diclofenac, and to a lower extent norfloxacin > ciprofloxacin > clarithromycin. The monitored pharmaceutical mixtures are expected to exert severe ecological risks in areas downstream of WWTP discharges, with the percentage of aquatic species affected ranging between 65% and 82% in 3 out of the 19 evaluated sites. In addition, five antibiotics were found to exceed antibiotic resistance thresholds, thus potentially contributing to resistance gene enrichment in environmental bacteria. This work illustrates the wide use and impact of pharmaceuticals in the area under study, and the vulnerability of surface waters if only conventional wastewater treatments are applied. Several compounds included in this study should be incorporated in future water monitoring programs to help in the development of future regulations, due to their potential risk to the aquatic environment

Recombinant Technology in the Development of Materials and Systems for Soft-Tissue Repair

Producción CientíficaThe field of biomedicine is constantly investing significant research efforts in order to gain a more in-depth understanding of the mechanisms that govern the function of body compartments and to develop creative solutions for the repair and regeneration of damaged tissues. The main overall goal is to develop relatively simple systems that are able to mimic naturally occurring constructs and can therefore be used in regenerative medicine. Recombinant technology, which is widely used to obtain new tailored synthetic genes that express polymeric protein-based structures, now offers a broad range of advantages for that purpose by permitting the tuning of biological and mechanical properties depending on the intended application while simultaneously ensuring adequate biocompatibility and biodegradability of the scaffold formed by the polymers. This Progress Report is focused on recombinant protein-based materials that resemble naturally occurring proteins of interest for use in soft tissue repair. An overview of recombinant biomaterials derived from elastin, silk, collagen and resilin is given, along with a description of their characteristics and suggested applications. Current endeavors in this field are continuously providing more-improved materials in comparison with conventional ones. As such, a great effort is being made to put these materials through clinical trials in order to favor their future use.Ministerio de Industria, Economía y Competitividad (proyectos PRI-PIBAR-2011–1403, MAT2012–38043, MAT2013–42473-R y MAT2013–41723-R)Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA152A12, VA155A12 y VA313U14)CIBER-BBN, y la Junta de Castilla y León y el Instituto de Salud Carlos III mediante el "Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León

Bioactive scaffolds based on elastin-like materials for wound healing

Producción CientíficaWound healing is a complex process that, in healthy tissues, starts immediately after the injury. Even though it is a natural well-orchestrated process, large trauma wounds, or injuries caused by acids or other chemicals, usually produce a non-elastic deformed tissue that not only have biological reduced properties but a clear aesthetic effect. One of the main drawbacks of the scaffolds used for wound dressing is the lack of elasticity, driving to non-elastic and contracted tissues. In the last decades, elastin based materials have gained in importance as biomaterials for tissue engineering applications due to their good cyto- and bio-compatibility, their ease handling and design, production and modification. Synthetic elastin or elastin like-peptides (ELPs) are the two main families of biomaterials that try to mimic the outstanding properties of natural elastin, elasticity amongst others; although there are no in vivo studies that clearly support that these two families of elastin based materials improve the elasticity of the artificial scaffolds and of the regenerated skin. Within the next pages a review of the different forms (coacervates, fibres, hydrogels and biofunctionalized surfaces) in which these two families of biomaterials can be processed to be applied in the wound healing field have been done. Here, we explore the mechanical and biological properties of these scaffolds as well as the different in vivo approaches in which these scaffolds have been used.Ministerio de Economía, Industria y Competitividad (Projects MAT2015-68901-R, MAT2016-78903-R, PCIN-2015-010)Junta de Castilla y León (programa de apoyo a proyectos de investigación - Ref. VA015U16)European Commission (ELASTISLET N. 646075