F. Javier Arias

• Graduate in Chemistry; Doctor in Medicine PhD (Biochemistry)
• Professor (Full) at University of Valladolid

New strategies to develop drug-loaded nanocarriers with improved therapeutic efficacy are needed for cancer treatment. Herein we report a novel drug-delivery nanosystem comprising encapsulation of the chemotherapeutic drug docetaxel (DTX) and recombinant fusion of a small peptide inhibitor of Akt kinase within an elastin-like recombinamer (ELR) veh...

The 3D printing of titanium (Ti) offers countless possibilities for the development of personalized implants with suitable mechanical properties for different medical applications. However, the poor bioactivity of Ti is still a challenge that needs to be addressed to promote scaffold osseointegration. The aim of the present study was to functionali...

Despite the promising potential of hydrogel-based therapeutic approaches for spinal cord injury (SCI), the need for new biomaterials to design effective strategies for SCI treatment and the outstanding properties of silk-elastin-like polymers (SELP), the potential use of SELPs in SCI is currently unknown. In this context, we assessed the effects el...

In this chapter we describe two unconventional strategies for the formulation of new nanovaccines. Both strategies are based on obtaining chimeric genes that code for proteins in which the major antigens of the pathogens are fused to an elastin-like recombinamer (ELR) as carrier. ELRs are a family of synthetic protein biopolymers obtained using DNA...

The concept of cancer as a systemic disease, and the therapeutic implications of this, has gained special relevance. This concept encompasses the interactions between tumor and stromal cells and their microenvironment in the complex setting of primary tumors and metastases. These factors determine cellular co-evolution in time and space, contribute...

Elastin polypeptides based on -VPGVG- repeated motifs are widely used in the production of biomaterials because they are stimuli-responsive systems. On the other hand, glycine-rich sequences, mainly present in tropoelastin terminal domains, are responsible for the elastin self-assembly. In a previous study, we have recombinantly expressed a chimeri...

Cancer has reached pandemic dimensions in the whole world. Although current medicine offers multiple treatment options against cancer, novel therapeutic strategies are needed due to the low specificity of chemotherapeutic drugs, undesired side effects and the presence of different incurable types of cancer. Among these new strategies, nanomedicine...

This study presents a new groundbreaking methodology for integrating innovative concepts to develop novel drug-delivery strategies. This methodology combines genetically engineered elastin-like recombinamers (ELRs) with supercritical fluid (SCF) techniques to encapsulate a poorly water-soluble drug in a one-step process. The chemotherapeutic agent...

Biomaterials science is one of the most rapidly evolving fields in biomedicine. However, although novel biomaterials have achieved well-defined goals, such as the production of devices with improved biocompatibility and mechanical properties, their development could be more ambitious. Indeed, the integration of active targeting strategies has been...

One of the main goals in both tissue engineering and regenerative medicine is to design innovative synthetic scaffolds that can simulate and control the communication pathways between cells and the extracellular matrix (ECM). In this context, we describe herein the characterization of protein polymer, a recombinant elastin-like recombinamer (ELR) d...

Coronary artery disease (CAD) is the most common cardiovascular disorder. Vascular surgery strategies for coronary revascularization (either percutaneous or open) show a high rate of failure because of restenosis of the vessel, due to phenotypic switch of vascular smooth muscle cells (VSMCs) leading to proliferation and migration. We have previousl...

Complex recombinant biomaterials that merge the self‐assembling properties of different (poly)peptides provide a powerful tool for the achievement of specific structures, such as hydrogel networks, by tuning the thermodynamics and kinetics of the system through a tailored molecular design. In this work, elastin‐like (EL) and silk‐like (SL) polypept...

This work analyzes the immunogenicity of six genetically engineered constructs based on Elastin-Like Recombinamers (ELRs) fused to the Gn glycoprotein from Rift Valley fever virus (RVFV). Upon transfection, all constructs showed no effect on cell viability. While fusion constructs including ELR blocks containing hydrophobic amino acids (alanine or...

The complexity and continuous evolution of cancer make the design of novel strategies of treatment a constant challenge in biomedicine. Moreover, most of cancer treatments are still not tumor-specific and provoke high systemic toxicity. Herein we have developed a novel selective nanodevice to eliminate tumor cells while leaving healthy ones intact....

Protein-based polymers are some of the most promising candidates for a new generation of innovative biomaterials as recent advances in genetic-engineering and biotechnological techniques mean that protein-based biomaterials can be designed and constructed with a higher degree of complexity and accuracy. Moreover, their sequences, which are derived...

This work investigates the physicochemical properties and in vitro accuracy of a genetically engineered drug delivery system based on elastin-like block recombinamers. The DNA recombinant technics allowed us to create this smart complex polymer containing bioactive sequences for internalization, lysosome activation under acidic pH and blockage of c...

Herein we present a novel one-pot method for the chemical modification of elastin-like recombinamers (ELRs) in a mild and efficient manner involving enzymatic catalysis with Candida antarctica lipase B. The introduction of different functionalities into such ELRs could open up new possibilities for the development of advanced biomaterials for regen...

Introduction Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine kinase 1 (SK1) is a proto-oncogene that is highly expressed in breast cancer, especially in oestrogen receptor (ER) negative tumours. SK1 inhibitor FTY720 has promising anticancer properties as monothrerapy. In...

Protein-based polymers are some of the most promising candidates for a new generation of innovative biomaterials as recent advances in genetic-engineering and biotechnological techniques mean that protein-based biomaterials can be designed and constructed with a higher degree of complexity and accuracy. Moreover, their sequences, which are derived...

This work focuses on improving the effectiveness of current therapies against glaucoma by incorporating self-assembled polymers into the ophthalmic formulation. To that end, we first studied the influence of the dispersing medium on the mechanical performance of self-assembling elastin-like (EL) and silk-elastin like (SEL) hydrogels by conducting r...

Biocompatibility studies, especially innate immunity induction, in vitro and in vivo cytotoxicity, and fibrosis, are often lacking for many novel biomaterials including recombinant protein-based ones, such as elastin-like recombinamers (ELRs), and has not been extensively explored in the scientific literature, in contrast to traditional biomaterial...

Over the last decades, novel therapeutic tools for osteochondral regeneration have arisen from the combination of mesenchymal stromal cells (MSCs) and highly specialized smart biomaterials, such as hydrogel-forming elastin-like recombinamers (ELRs), which could serve as cell-carriers. Herein, we evaluate the delivery of xenogeneic human MSCs (hMSCs...

In the last decade, recombinant structural proteins have become very promising in addressing different issues like 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, like hydrogels. Furthermo...

Endoglin (CD105) is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenograft...

Targeted drug delivery is a new multidisciplinary field that aims to develop innovative nanomaterials, tools and devices to deploy a therapeutic agent to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. Advanced drug-delivery systems attempt to control the site of action and release...

Background: Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especial...

The search for new and biocompatible materials with high potential for improvement is a challenge in gene delivery applications. A cell type specific vector made of elastin-like recombinamer (ELR) and aptamers has been specifically designed for the intracellular delivery of therapeutic material for breast cancer therapy. A lysine enriched ELR was c...

Drug delivery systems that are able to control site and rate release of bioactive molecules are of particular interest for tissue therapy. Systems comprising biocompatible materials that can respond to environmental stimuli include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, which are especia...

The use of recombinant elastin-like materials, or elastin-like recombinamers (ELRs), in drug-delivery applications is reviewed in this work. Although ELRs were initially used in similar ways to other, more conventional kinds of polymeric carriers, their unique properties soon gave rise to systems of unparalleled functionality and efficiency, with t...

Transversality between mathematical modeling, pharmacology, and materials science is essential in order to achieve controlled-release systems with advanced properties. In this regard, the area of biomaterials provides a platform for the development of depots that are able to achieve controlled release of a drug, whereas pharmacology strives to find...

Many biological processes are regulated by reversible binding events, with these interactions between macromolecules representing the core of dynamic chemistry. As such, any attempt to gain a better understanding of such interactions, which would pave the way to the extrapolation of natural designs to create new advanced systems, is clearly of inte...

INTRODUCTION Elastin-like recombinamers are natural elastin derived polypeptides with growing applications in the biomedicine fields1-3. The use of genetic engineering techniques allow the total control over their chemical and physical features such as surface charge, polydispersity, self-assembly and biocompatibility. The design of positively char...

This review discusses the use of elastin-like polymers and their recombinant version, elastin-like recombinamers, in drug-delivery systems. These macromolecules exhibit a number of interesting properties that are rarely found together in any other family of materials, especially extremely high biocompatibility, high bioactivity and functionality, c...

A bioactive and multifunctional elastin-like polymer (ELP) was produced by genetic engineering techniques to develop new artificial matrices with the ability to mimic the extracellular matrix (ECM). The basic composition of this ELP is a thermo- and pH-sensitive elastin pentapeptide which has been enriched with RGD-containing domains, the RGD loop...

In this work, well defined elastin-like recombinamers (ELRs) were studied as a choice to the existing non-viral vectors due to their biocompatibility and ease of scale-up. Functional motifs, namely penetratin and LAEL fusogenic peptides were incorporated into a basic ELR sequence, and imidazole groups were subsequently covalently bound obtaining EL...

Although significant progress has been made in the area of injectable hydrogels for biomedical applications and model cell niches, further improvements are still needed, especially in terms of mechanical performance, stability and biomimicry of the native fibrillar architecture found in the extracellular matrix (ECM). This work focuses on the desig...

Elastin like recombinamers (ELRs) are smart, genetically engineered biomaterials inspired in natural elastin and based in the recurring amino-acid sequences found in tropoelastin. ELRs as recombinant artificial polypeptides can be tuned to change their properties by adjusting the aminoacid composition of the sequence. Increasing the net charge of t...

Multilayered microcapsules of chitosan and biomimetic elastin-like recombinamers (ELRs) were prepared envisaging the intracellular delivery of active agents. Two ELRs containing either a bioactive RGD sequence or a scrambled nonfunctional RDG were used to construct two types of functionalized polymeric microcapsules, both with spherical shape about...

The emergence of the new scientific field known as nanomedicine is being catalyzed by multiple improvements in nanoscience techniques and significant progress in materials science, especially as regards the testing of novel and sophisticated biomaterials. This conjuncture has furthered the development of promising instruments in terms of detection,...

In drug delivery there has been great interest in the development of nano- and microcarriers of active agents to control their release kinetics and their efficacy by delivering them to where they are most needed. A possible method of delivery is that of carrier internalization by cells. By delivering an active agent directly to the cells, high drug...

Layer-by-layer (LbL) is a mild and versatile surface modification technique that allows producing robust coatings even in substrates with complex geometries. Taking advantage of the 3D possibilities opened by LbL, we present customized compartmentalized capsules inspired by the complex structure of cells, with temperature and magnetic-based respons...

The creation of a gene delivery carrier suitable to release the therapeutic gene in the site of action is a challenge in the nanomedicine area. Elastin like recombinamers (ELRs) as recombinant artificial polypeptides whose sequence or a main part of it, mimics the repeated motifs found in natural elastin has been shown as a biocompatible material a...

Inspired by the cells' structure, we present compartmentalized capsules with temperature and magnetic-based responsiveness, and hierarchical organization ranging from the nano- to the visible scales. Liquefied alginate macroscopic beads coated with a layer-by-layer (LbL) chitosan/alginate shell served as containers both for model fluorophores and m...

Nanostructured films consisting of polysaccharides and elastin-like recombinamers (ELRs) are fabricated in a layer-by-layer manner. A quartz-crystal microbalance with dissipation monitoring (QCM-D) is used to follow the build-up of hybrid films containing one polysaccharide (chitosan or alginate) and one of several ELRs that differ in terms of amin...

A wide range of smart surfaces with novel properties relevant for biomedical applications have been developed recently. Herein we focus on thermoresponsive surfaces that switch between cell-adherent and non-adherent states, and their applications for cell harvesting. These smart surfaces are obtained by covalently coupling a tailored Elastin-Like R...

Unlabelled: Multilayer capsules conceived at the nano- and microscales are receiving increasing interest due to their potential role as carriers of biomolecules for drug delivery and tissue engineering. Herein we report the construction of microcapsules by the sequential adsorption of chitosan and a biomimetic elastin-like recombinamer into nanost...

Silk-elastin-like polymers (SELPs) are protein-based polymers composed of repetitive amino acid sequence motifs found in silk fibroin (GAGAGS) and mammalian elastin (VPGVG). These polymers are of much interest, both from a fundamental and applied point of view, finding potential application in biomedicine, nanotechnology and as materials. The succe...

Nucleotide and amino acid sequences of SELP constructions.

Tetrazolium salt (MTS) test performed on C2C12 cells as a function of the concentration of SELP-1020-A and SELP-59-A. Short term cell viability tests in response to SELP copolymer were performed by the MTS assay using the supplier’s recommended procedure (Promega). One millilitre of C2C12 cells at a concentration of 5 x 104 cells/mL were seeded in...

This study investigates both the physicochemical properties and immunogenicity of a genetically engineered elastin-like block co-recombinamer (ELbcR) containing a major membrane protein sequence from Mycobacterium tuberculosis. The recombinant production of this ELbcR allows the production of large quantities of safe, antigenic particle-based const...

In this chapter, we describe two methods for bio-producing recombinant repetitive polypeptide polymers for use in biomedical devices. These polymers, known as elastin-like recombinamers (ELRs), are derived from the repetition of selected amino acid domains of extracellular matrix proteins with the aim of recreating their mechanical and physiologica...

Layer-by-layer (LbL) has been presented as a tool capable of constructing tunable and sustained release reservoirs for therapeutic and proliferation/differentiation agents. We report the conception of biocompatible stimuli-responsive microcapsules fabricated using LbL containing BSA as model protein. The capsules were constructed by the sequential...

This work explores cell behavior as a function of the topographic (fibers vs. films) and bioactive (RGD inclusion) design of multifunctional surfaces obtained from elastin-like recombinamers (ELRs). The surfaces have been analyzed for their differential roughness, wettability, and surface free-energy, as their precise contribution and importance of...

Actualmente, una de las técnicas más ampliamente utilizadas en la purificación de proteínas recombinantes es la cromatografía de afinidad. Sin embargo, esta técnica es costosa, requiere de equipo especializado y es difícil de escalar. Por tanto, es deseable el desarrollo de métodos más económicos y técnicamente más sencillos. Uno de estos métodos e...

The past few decades have witnessed the development of novel naturally inspired biomimetic materials, such as polysaccharides and proteins. Likewise, the seemingly exponential evolution of genetic-engineering techniques and modern biotechnology has led to the emergence of advanced protein-based materials with multifunctional properties. This approa...

In this work, biomimetic smart thin coatings using chitosan and a recombinant elastin-like recombinamer (ELR) containing the cell attachment sequence arginine-glycine-(aspartic acid) (RGD) are fabricated through a layer-by-layer approach. The synthetic polymer is characterized for its molecular mass and composition using mass spectroscopy and pepti...

Objectives: Polyelectrolyte vesicles using layer-by-layer (LbL) were recently introduced for the encapsulation of therapeutic molecules. This work presents multilayered microcapsules of chitosan and a temperature-responsive elastin-like recombinamer (ELR) as a novel drug delivery system. The release of a pre-loaded model protein was studied at dist...

Introduction. The design of smart and nanostructured surfaces has allowed to achieve significant advances in tissue engineering. Emphasis has been given to layer-by-layer (LbL) adsorption of polymers for being a simple and versatile technique. In this study, we report the use of chitosan and an elastin-like recombinamer (ELR) containing RGD to prod...

Biomimetic hybrid materials based on a polymeric and an inorganic component such as calcium phosphate are potentially useful for bone repair. The current study reports on a new approach toward biomimetic hybrid materials using a set of recombinamers (recombinant protein materials obtained from a synthetic gene) as crystallization additive for calci...

Elastin-like recombinamers have grown in popularity in the field of protein-inspired biomimetic materials and have found widespread use in biomedical applications. Modern genetic-engineering techniques have allowed the design of multifunctional materials with an extraordinary control over their architecture and physicochemical properties, such as s...

The rapid development of polymer science has led to literally thousands of different monomers and an almost endless number of possibilities arising from their combination. The most promising strategy to date has been to consider natural products as macromolecules that provide the best option for obtaining functional materials. Proteins, with their...

In living organisms, there are phenomena that require the presence of specific biomolecules with distinct function and in variable concentrations at a given time, such as the healing and regeneration of tissue and organ lesions. In this work, we propose the use of a compartmented drug delivery device for the multiple release of bioactive agents. It...

Abstract The design and synthesis of nanostructured functional hybrid biomaterials are essential for the next generation of advanced diagnostics and the treatment of disease. A simple route to fabricate semiconductor nanofibers by self-assembled, elastin-like polymer (ELP)-templated semiconductor nanoparticles is reported. Core–shell nanostructures...

Here, we describe a procedure to manufacture smart hybrid probes that exhibit tunable optical properties as a function of multiple environmental variations. Initially, we achieved a one‐pot synthesis of gold‐PREP (photo‐responsive elastin‐like polymer) conjugate Gold‐AzoGlu15 via reduction of auric acid in the presence of PREP AzoGlu15 . Outstandin...

We report a simple, fast, water-based method to obtain micropatterned biocompatible gels from a recently described family of elastin-like amphiphilic multiblock copolymers that combines reversible thermogelling properties under mild, physiological conditions with a means of replica molding.

Chitosan and an elastin-like polymer, containing a specific osteoconductive sequence in the primary structure, have been combined to obtain bioactive injectable systems with enhanced mechanical properties and hydrogels. Obtained results indicate that the combination of such polymers may be very promising in the development of biomaterials for minim...

Smart thin coatings using a recombinant elastin-like polymer (ELP) containing the cell attachment sequence arginine–glycine–(aspartic acid) (RGD) are fabricated for the first time through simple deposition of the ELP dissolved in aqueous-based solutions. The biopolymer is produced and characterized using electrophoresis and mass spectroscopy. The t...

Costa et al. successfully apply a simple protein adsorption technique combining chitosan substrates and recombinant elastin-like polymers (ELPs) on page 3210. This process allows for coating of polysaccharide substrates with such biomimetic macromolecules, resulting in interesting properties such as smart behavior and improved cell adhesion. The fi...

Biotechnology offers powerful solutions to the challenges that arise during the design and development of new complex biomimetic materials to achieve specific biological responses. Recombinant DNA technologies, in particular, provide unique solutions in the biomaterials field, especially regarding the control of macromolecular architectures involvi...

Multifunctional bioactive chemically cross-linked elastin-like polymers (ELPs) have been prepared as three-dimensional scaffolds for tissue engineering. The salt-leaching/gas-foaming technique was found suitable to prepare highly porous biodegradable hydrogels based on this novel material type. The porosity can be controlled by the amount of sodium...

This work explores the dependence of the inverse temperature transition of elastin-like polymers (ELPs) on the amino-acid sequence, i.e., the amino-acid arrangement along the macromolecule and the resulting linear distribution of the physical properties (mainly polarity) derived from it. The hypothesis of this work is that, in addition to mean pola...

Genetic engineering was used to produce an elastin-like polymer (ELP) with precise amino acid composition, sequence and length, resulting in the absolute control of MW and stereochemistry. A synthetic monomer DNA sequence encoding for (VPAVG)20, was used to build a library of concatemer genes with precise control on sequence and size. The higher mo...

La matriz extracelular es uno de los principales elementos reguladores de la actividad celular. Los diferentes módulos de las macromoléculas que la componen son capaces de desencadenar señales que activan diferentes rutas intracelulares que organizan las funciones vitales de las células. La ingeniería de tejidos se dedica a desarrollar sistemas cap...

To investigate epithelial cell adhesion and proliferation on a newly developed elastin-like polymer (ELP) that mimics the functional characteristics of extracellular matrices. A genetically engineered ELP with cell attachment sequences was adsorbed onto glass coverslips as 1, 2, or 3 molecular films. Conjunctival epithelial cells from a human cell...

An elastin-like polymer (ELP) was designed by genetic engineering techniques to mimic the extracellular matrix (ECM). The precise control of the polymer sequence offered many advantages that allowed the definition of distinct and specific domains. The cell attachment domain present in the sequence enhances the cell adhesion. Hexamethylene diisocyan...

Two different ELPs have been designed and selected for the purpose of this work. The first one is ((VPGVG)2-(VPGEG)-(VPGVG)2)n where E stands for L-Glutamate. This polypeptide exhibits the same properties than the model polymer (VPGVG)n and in addition a pH-sensitive nature produced for the change in polarity in the protonation-deprotonation of the...

Elastin-like polymers (ELPs) are based on repeating sequences found in the natural elastin. They show remarkable combination of properties, such as a large range of mechanical properties, excellent biocompatibility, and smart behaviour and self-assembly towards temperature, pH and often different stimuli. Around a certain temperature, known as inve...

Using 1H and 13C 1D and 2D NMR spectra, relaxation and PFG NMR measurements, the structural changes of two genetically engineered, and thus unimolecular, elastin-like polypentapeptides [(GVGVP)2-(GEGVP)-(GVGVP)2]n, n = 9 and 15, in D2O and H2O solutions and at two concentrations (5 and 0.5% wt), were studied in the temperature interval 288–330 K, i...

Elastin-like recombinant protein polymers are a new family of polymers which are captivating the attention of a broad audience ranging from nanotechnologists to biomaterials and more basic scientists. This is due to the extraordinary confluence of different properties shown by this kind of material that are not found together in other polymer syste...

Today, the development of advanced biomaterials is still lacking an appropriate tailored engineering approach. Most of the biomaterials currently used have their origin in materials developed for other technological applications. This lack of adequate biomaterial design is probably due to the peculiar environment where those materials must operate....

a comparative view on host physiology The organisers would like to thank Novozymes Delta Ltd who generously supported the meeting. Meeting

The genetic engineering of protein-based polymers is a method that enables, in an easy way, the design of complex and highly functional macromolecules. As examples of this approach, different molecular designs are presented, with increasing degree of complexity, showing how the controlled increase in their complexity yields (multi)functional materi...

In spite of the enormous possibilities of macromolecules as key elements in developing advanced materials with increased functionality and complexity, the success in this development is often limited by the randomness associated with polymer synthesis and the exponential increase in technical difficulties caused by the attempt to reach asufficientl...