Networking Research Center on Bioengineering

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Networking Research Center on Bioengineering

United States

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Bosch R.,Biomedical Research Institute Sant Pau | Bosch R.,Networking Research Center on Bioengineering | Dieguez-Gonzalez R.,Biomedical Research Institute Sant Pau | Cespedes M.V.,Biomedical Research Institute Sant Pau | And 11 more authors.
Blood | Year: 2011

Focal adhesion (FA) proteins have been associated with transformation, migration, metastasis, and poor outcome in many neoplasias. We previously showed that these proteins were inhibited by E7123, a new celecoxib derivative with antitumor activity, in acute myeloid leukemia. However, little is known about FAs in diffuse large B cell lymphoma (DLBCL). This paper aimed to determine whether E7123 was effective against DLBCL and whether FAs were involved in its action. We evaluated the cytotoxicity and mechanism of action of E7123 and celecoxib in DLBCL cell lines. We also assessed the E7123 in vivo activity in a DLBCL xenograft model and studied FA signaling in primary DLBCLpatient samples.We found that E7123 showed higher antitumor effect than celecoxib against DLBCL cells. Its mechanism of action involved deregulation of FA, AKT, and Mcl-1 proteins, a pathway that is activated in some patient samples, apoptosis-inducing factor release and induction of caspase-independent cell death. Moreover, E7123 showed suppression of in vivo tumor growth. These findings indicate that E7123 is effective against DLBCL in vitro and in vivo, with a mechanism of action that differs from that of most current therapies for this malignancy. Our results support further preclinical evaluation of E7123. © 2011 by The American Society of Hematology.


Alcaide M.,Complutense University of Madrid | Portoles P.,Institute Salud Carlos III | Lopez-Noriega A.,Complutense University of Madrid | Lopez-Noriega A.,Networking Research Center on Bioengineering | And 5 more authors.
Acta Biomaterialia | Year: 2010

Ordered mesoporous 85SiO2-10CaO-5P2O5 bioactive glass (MBG85) is an excellent candidate as a graft for bone tissue regeneration, owing to its excellent textured properties, structural characteristics and crystalline apatite rate formation. To assess MBG85 biocompatibility, different parameters have been evaluated (cell morphology, size/complexity, proliferation, viability, cell cycle, reactive oxygen species content, lactate dehydrogenase release) using human Saos-2 osteoblasts after treatment with either MBG85 extracts or 1% MBG85 directly added to cells. The osteoblast response to MBG85 was compared with L929 fibroblast behaviour after the same treatment. The high cell viability observed and the absence of signs of cell damage in both cell types demonstrates MBG85 biocompatibility. Only a cytostatic effect was observed through the reduction of cell proliferation, related with the initial Ca elution, whereas Si leaching did not result into any negative effect. In vitro lymphocytic proliferation analysis was also carried out with SR.D10 clone after treatment with either MBG85 extracts or culture supernatants of L929 fibroblasts previously treated with 1% MBG85 (cell-conditioned extracts). The absence of modification of in vitro T-cell response underlines the biocompatibility of MBG85 and its potential application in the field of bone and dental grafting. © 2009 Acta Materialia Inc.


Gil-Albarova J.,University of Zaragoza | Vila M.,Complutense University of Madrid | Vila M.,Networking Research Center on Bioengineering | Badiola-Vargas J.,University of Zaragoza | And 5 more authors.
Acta Biomaterialia | Year: 2012

The main requirement of bone regenerative scaffolds is to enhance the chemical reactions leading to the formation of new bone while providing a proper surface for tissue in-growth as well as a suitable degradation rate. Calcium phosphate ceramics are conformed by different shaping methods. One requirement is to design implants and scaffolds with suitable shapes and sizes, but also with interconnected porosity to ensure bone oxygenation and angiogenesis. In this work we present the in vivo performance of hierarchically arranged glutaraldehyde crosslinked, gelatin-coated nanocrystalline hydroxyapatite (HABP) scaffolds (1-400 μm), with high potential as bone regenerators and excellent osteointegration performance, as well as an appropriate bioresorption rate. 6 × 10 mm bone defects were made in the lateral aspect of both distal femoral epiphysis of 15 mature (9 months old) male New Zealand rabbits. The bone defect in the left femur was then filled by using HABP foam cylinders, allowing the surgeon to carve the appropriate shape for a particular bone defect with high stability intra-operatively. The foam becomes swollen with body fluid and fills the cavity, ensuring good fixation without the need for a cement. Histological and radiographical studies after 4 months implantation showed healing of all treated bone defects, with bone integration of the HABP foam cylinders and bone conduction over the surface. This in vivo behaviour offers promising results as a scaffold for clinical applications, mainly in orthopaedics and dentistry. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Arnal-Pastor M.,Polytechnic University of Valencia | Valles-Lluch A.,Polytechnic University of Valencia | Valles-Lluch A.,Regenerative Medicine Unit | Keicher M.,Polytechnic University of Valencia | And 3 more authors.
Journal of Colloid and Interface Science | Year: 2011

A set of elastomeric scaffolds with a well defined porous structure was prepared with a template leaching procedure and coated with hyaluronic acid solutions. Depending on the coating process parameters the hyaluronic acid deposited on the pores had configurations ranging from thin disconnected aggregates to a thick continuous layer on the pore surface. The development of the coating layer was studied by scanning electron microscopy and the materials were subjected to dynamical and equilibrium swelling experiments in a water vapor ambient of fixed activity. The porosity change due to coating and to swelling of the coating layer were determined. The hyaluronic acid coating the pores has a different swelling capacity depending on the type of layer formed, as a consequence of the scaffold constraint and of the layer typology. These factors were investigated analytically by modifying the standard theory of gel swelling. An experimental quantity is introduced which reflects the constrainment build-up on gel swelling. © 2011 Elsevier Inc.


Valles-Lluch A.,Polytechnic University of Valencia | Poveda-Reyes S.,Polytechnic University of Valencia | Amoros P.,University of Valencia | Beltran D.,University of Valencia | And 2 more authors.
Biomacromolecules | Year: 2013

Excessive water sorption and low mechanical properties are a severe drawback in some biomedical applications of hyaluronic acid (HA). A way to improve these properties is here explored through the novel concept of nanohybrid hydrogels consisting of a HA matrix including different amounts of silica-derived species. This inorganic filler phase controls the mechanical and swelling properties of HA cross-linked matrices. Below a 2 wt % of silica in the systems, nanoparticle aggregates of tens of nanometers and silica oligomers are distributed more or less homogeneously throughout the organic matrix, without percolating. This morphology of the silica phase is accompanied by an increased swelling degree of the composite when compared with pure HA. For higher silica mass ratios in the composites the inorganic counterpart coalesces, leading to a continuous inorganic silica network interpenetrated with the organic HA network, which coexists with a dispersed phase of silica-nanoparticle aggregates. Silica oligomers originating in the exposition of the nanoparticles to reactives during the composite preparation procedure contribute to the continuity of the silica network. For these compositions, swelling is reduced three times when compared with pure HA, and a significant improvement of the mechanical properties occurs. Water-containing samples of these materials exhibited a glass transition, which pure dry HA does not. None of the compositions studied showed any cytotoxicity. Thus, the materials could be of use in tissue engineering applications where these properties of HA need to be modulated. © 2013 American Chemical Society.


Valles-Lluch A.,Polytechnic University of Valencia | Valles-Lluch A.,Regenerative Medicine Unit | Gallego Ferrer G.,Polytechnic University of Valencia | Gallego Ferrer G.,Regenerative Medicine Unit | And 4 more authors.
European Polymer Journal | Year: 2010

Poly(ethyl methacrylate-co-hydroxyethyl acrylate) 70/30 %wt/silica, P(EMA-co-HEA)/SiO2, nanocomposites, with silica contents ranging from 0 to 30 %wt, were synthesized and studied as promising candidate materials for the synthetic matrix of scaffolds for bone substitutes or dentin regeneration. The physico-chemical properties of the hybrids were studied by calorimetry and by contact angle measurements on the surfaces. The dynamic-mechanical and compression properties were analysed. Intermediate silica contents in the range from 10 to 20 %wt of silica rendered co-continuous interpenetrated structures, in which silica produced a reinforcing effect in the polymeric matrix and at the same time conferred bioactivity to the surfaces by improving surface wettability, making these hybrids appropriate for the proposed application. On the contrary, silica percentages below 10 %wt formed disconnected inorganic aggregates at the nanoscale dispersed in the copolymer matrix, which did not modify significantly the copolymer properties. Silica contents above 20 %wt formed denser inorganic networks with few terminal silanol groups available at the surfaces, much more rigid and hardly manageable samples. © 2010 Elsevier Ltd. All rights reserved.


Castillo-Fernandez O.,Institute for Bioengineering of Catalonia | Castillo-Fernandez O.,University of Barcelona | Castillo-Fernandez O.,Networking Research Center on Bioengineering | Salieb-Beugelaar G.B.,University of Twente | And 7 more authors.
Electrophoresis | Year: 2011

The electrokinetic transport behavior of λ-DNA (48kbp) in 20nm-high fused-silica nanoslits in the presence of short-chain PVP is investigated. Mobility and video data show a number of phenomena that are typical of DNA transport through gels or polymer solutions, thus indicative of rigid migration obstacles in the DNA pathway. Calculations show that a several nanometer thin layer of wall-adsorbed PVP ('nano-gel') can provide such a rigid obstacle matrix to the DNA. Such ultrathin wall-adsorbed polymer layers represent a new type of matrix for electrokinetic DNA separation. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Alvarez S.,Hospital General Universitario Gregorio Maranon | Alvarez S.,Institute Investigacion Sanitaria Gregorio Maranon | Munoz-Fernandez M.A.,Hospital General Universitario Gregorio Maranon | Munoz-Fernandez M.A.,Institute Investigacion Sanitaria Gregorio Maranon | Munoz-Fernandez M.A.,Networking Research Center on Bioengineering
PLoS ONE | Year: 2013

Members of the mammalian nucleotide binding domain, leucine-rich repeat (LRR)-containing receptor family of proteins are key modulators of innate immunity regulating inflammation. To date, microbial pathogen-associated molecules and toxins have been identified as key triggers of activation of inflammasomes. However, recently, environmental, and neurodegenerative stimuli have been identified that lead to IL-1β release by means of inflammasomes. IL-1β plays a crucial role during brain inflammation, and caspase-1 appears to be a key modulator of IL-1β bioactivity and the consequent transcriptional regulation of gene expression within the brain during inflammation. We show here that exposure of a human neuroblastoma cell line (SK-N-MC cells) to TNF-α promotes ROS-mediated caspase-1 activation and IL-1β secretion. The involvement of NF-κB in the regulation of IL-1β synthesis is investigated through specific inhibition of this transcription factor. The effect of TNF-α was abolished in the presence of ROS inhibitors as NAC, or DPI. Remarkably, SK-N-MC cells do not respond to ATP stimulation in spite of P2X7R expression. These results provide a mechanism by which danger signals and particulate matter mediate inflammation via the inflammasome in the absence of microbial infection. © 2013 Álvarez, Muñoz-Fernández.


Arnal-Pastor M.,Polytechnic University of Valencia | Martinez Ramos C.,Polytechnic University of Valencia | Perez Garnes M.,Polytechnic University of Valencia | Monleon Pradas M.,Polytechnic University of Valencia | And 2 more authors.
Materials Science and Engineering C | Year: 2013

A procedure to obtain electrospun mats of hyaluronic acid (HA) stable in aqueous media in one single step has been developed. It consists in combining an HA solution with a divinyl sulfone one as cross-linker in a three-way valve to immediately electroblow their mixture. Membranes obtained with this method, after sterilization and conditioning, are ready to use in cell culture without need of any additional post-treatment. HA nanofibers are deposited onto previously electrospun poly(l-lactic acid) (PLLA) mats in order to obtain stably joined bilayered membranes with an adherent face and the opposite face non-adherent, despite their different hydrophilicity and mechanical properties. These bilayered HA/PLLA membranes may be of use, for example, in applications seeking to transplant cells on a tissue surface and keep them protected from the environment: the PLLA nanofiber face is cell friendly and promotes cell attachment and spreading and can thus be used as a cell supply vehicle, while the HA face hinders cell adhesion and thus may prevent post-surgical adherences, a major issue in many surgeries. © 2013 Elsevier B.V.


Arnal-Pastor M.,Polytechnic University of Valencia | Perez-Garnes M.,Polytechnic University of Valencia | Monleon Pradas M.,Polytechnic University of Valencia | Monleon Pradas M.,Networking Research Center on Bioengineering | Valles Lluch A.,Polytechnic University of Valencia
Colloids and Surfaces B: Biointerfaces | Year: 2016

Scaffolds based on poly(ethyl acrylate) having interwoven channels were coated with a hyaluronan (HA) hydrogel to be used in tissue engineering applications. Controlled typologies of coatings evolving from isolated aggregates to continuous layers, which eventually clog the channels, were obtained by using hyaluronan solutions of different concentrations. The efficiency of the HA loading was determined using gravimetric and thermogravimetric methods, and the hydrogel loss during the subsequent crosslinking process was quantified, seeming to depend on the mass fraction of hyaluronan initially incorporated to the pores. The effect of the topologically different coatings on the scaffolds, in terms of mechanical properties and swelling at equilibrium under different conditions was evaluated and correlated with the hyaluronan mass fraction. The potential of these hydrogel coatings as vehicle for controlled drug release from the scaffolds was validated using a protein model. © 2016 Elsevier B.V.

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