1,721,007 research outputs found

    Biomaterials against Bone Infection

    No full text
    RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí) RESEARCHER ID B-5081-2017 (Daniel Lozano Borregón) ORCID 0000-0001-5902-9201 (Daniel Lozano Borregón) RESEARCHER ID K-4773-2015 (Blanca González Ortiz) ORCID 0000-0002-0493-6071 (Blanca González Ortiz) RESEARCHER ID M-9921-2014 (Isabel Izquierdo Barba) ORCID 0000-0002-4139-4646 (Isabel Izquierdo Barba)Chronic bone infection is considered as one of the most problematic biofilm-related infections. Its recurrent and resistant nature, high morbidity,prolonged hospitalization, and costly medical care expenses have driven the efforts of the scientific community to develop new therapies to improve the standards used today. There is great debate on the management of this kind of infection in order to establish consistent and agreed guidelines in national health systems. The scientific research is oriented toward the design of anti-infective biomaterials both for prevention and cure. The properties of these materials must be adapted to achieve better anti-infective performance and good compatibility, which allow a good integration of the implant with the surrounding tissue. The objective of this review is to study in-depth the antibacterial biomaterials and the strategies underlying them. In this sense, this manuscript focuses on antimicrobial coatings, including the new technological advances on surface modification; scaffolding design including multifunctional scaffolds with both antimicrobial and bone regeneration properties; and nanocarriers based on mesoporous silica nanoparticles with advanced properties (targeting and stimuli-response capabilities).European Research CouncilDepto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEpu

    Mesoporous silica nanoparticles decorated with polycationic dendrimers for infection treatment

    Get PDF
    RESEARCHER ID K-4773-2015 (Blanca González Ortiz) ORCID 0000-0002-0493-6071 (Blanca González Ortiz) RESEARCHER ID N-4628-2014 (Montse Colilla Nieto) ORCID 0000-0003-1961-4160 (Montse Colilla Nieto) RESEARCHER ID M-9921-2014 (Isabel Izquierdo Barba) ORCID 0000-0002-4139-4646 (Isabel Izquierdo Barba) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)This work aims to provide an effective and novel solution for the treatment of infection by using nanovehicles loaded with antibiotics capable of penetrating the bacterial wall, thus increasing the antimicrobial effectiveness. These nanosystems, named "nanoantibiotics", are composed of mesoporous silica nanoparticles (MSNs), which act as nanocarriers of an antimicrobial agent (levofloxacin, LEVO) localized inside the mesopores. To provide the nanosystem of bacterial membrane interaction capability, a polycationic dendrimer, concretely the poly(propyleneimine) dendrimer of third generation (G3), was covalently grafted to the external surface of the LEVOloaded MSNs. After physicochemical characterization of this nanoantibiotic, the release kinetics of LEVO and the antimicrobial efficacy of each released dosage were evaluated. Besides, internalization studies of the MSNs functionalized with the G3 dendrimer were carried out, showing a high penetrability throughout Gram-negative bacterial membranes. This work evidences that the synergistic combination of polycationic dendrimers as bacterial membrane permeabilization agents with LEVO-loaded MSNs triggers an efficient antimicrobial effect on Gram-negative bacterial biofilm. These positive results open up very promising expectations for their potential application in new infection therapies.Unión Europea. H2020Ministerio de Economía y Competitividad (MINECO)Instituto de Salud Carlos III (ISCIII)Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEpu

    Bacteria as Nanoparticles Carrier for Enhancing Penetration in a Tumoral Matrix Model

    No full text
    RESEARCHER ID M-9921-2014 (Isabel Izquierdo Barba) ORCID 0000-0002-4139-4646 (Isabel Izquierdo Barba) RESEARCHER ID K-8193-2014 (Alejandro Baeza) ORCID 0000-0002-2026-6266 (Alejandro Baeza) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)One of the major concerns in the application of nanocarriers in oncology is their scarce penetration capacity in tumoral tissues, which drastically compromises the effectivity. Living organisms as cells and bacteria present the capacity to navigate autonomously following chemical gradients being able to penetrate deeply into dense tissues. In the recent years, the possibility to employ these organisms for the transportation of therapeutic agents and nanocarriers attached on their membrane or engulfed in their inner space have received huge attention. Herein, based on this principle, a new approach to deliver drug loaded nanoparticles achieving high penetration in tumoral matrices is presented. In this case, Escherichia coli (E. coli) bacteria wall is decorated with azide groups, whereas alkyne-strained groups are incorporated on the surface of mesoporous silica nanoparticles loaded with a potent cytotoxic compound, doxorubicin. Both functional groups form stable triazole bonds by click-type reaction allowing the covalent grafting of nanoparticles on living bacteria. Thus, the motility and penetration capacity of bacteria, which carried nanoparticles are evaluated in a 3D tumoral matrix model composed by a dense collagen extracellular matrix with HT1080 human fibrosarcome cells embedded. The results confirmed that bacteria are able to transport the nanoparticles crossing a thick collagen layer being able to destroy almost 80% of the tumoral cells located underneath. These findings envision a powerful strategy in nanomedicine applied for cancer treatment by Q4 allowing a homogeneous distribution of therapeutic agents in the malignancy.Unión EuropeaDepto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEinpres

    Strontium-releasing mesoporous bioactive glasses with anti-adhesive zwitterionic surface as advanced biomaterials for bone tissue regeneration

    Get PDF
    RESEARCHER ID M-9921-2014 (Isabel Izquierdo Barba) ORCID 0000-0002-4139-4646 (Isabel Izquierdo Barba) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)Hypothesis The treatment of bone fractures still represents a challenging clinical issue when complications due to impaired bone remodelling (i.e. osteoporosis) or infections occur. These clinical needs still require a radical improvement of the existing therapeutic approach through the design of advanced biomaterials combining the ability to promote bone regeneration with anti-adhesive properties able to minimise unspecific biomolecules adsorption and bacterial adhesion. Strontium-containing mesoporous bioactive glasses (Sr-MBG), which are able to exert a pro-osteogenic effect by releasing Sr2+ ions, have been successfully functionalised to provide mixed-charge (-NH3 /-COO⊝) surface groups with anti-adhesive abilities. Experiments Sr-MBG have been post-synthesis modified by co-grafting hydrolysable short chain silanes containing amino (aminopropylsilanetriol) and carboxylate (carboxyethylsilanetriol) moieties to achieve a zwitterionic zero-charge surface. The final system was then characterised in terms of textural-structural properties, bioactivity, cytotoxicity, pro-osteogenic and anti-adhesive capabilities. Findings After zwitterionization the in vitro bioactivity was maintained, as well as the ability to release Sr2+ ions which are capable of inducing a mineralization process. Irrespective of their size, Sr-MBG particles did not exhibit any cytotoxicity in pre-osteoblastic MC3T3-E1 up to the concentration of 75 µg/mL. Finally, the zwitterionic Sr-MBGs showed a significant reduction of serum protein adhesion with respect to the pristine ones. These results open promising future expectations in the design of nanosystems which combine pro-osteogenic and anti-adhesive properties.Unión Europea. H2020Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEpu

    Concanavalin A-targeted mesoporous silica nanoparticles for infection treatment.

    Get PDF
    RESEARCHER ID N-3992-2014 (Marina Martínez Carmona) ORCID 0000-0002-2026-6266 (Marina Martínez Carmona) RESEARCHER ID M-9921-2014 (Isabel Izquierdo Barba) ORCID 0000-0002-4139-4646 (Isabel Izquierdo Barba) RESEARCHER ID N-4628-2014 (Montse Colilla Nieto) ORCID 0000-0003-1961-4160 (Montse Colilla Nieto) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)The ability of bacteria to form biofilms hinders any conventional treatment for chronic infections and has serious socio-economic implications. For this purpose, a nanocarrier capable of overcoming the barrier of the mucopolysaccharide matrix of the biofilm and releasing its loadedantibiotic within this matrix would be desirable. Herein, we developed a new nanosystem based on levofloxacin (LEVO)-loaded mesoporous silica nanoparticles (MSNs) decorated with the lectin concanavalin A (ConA). The presence of ConA promotes the internalization of this nanosystem into the biofilm matrix, which increases the antimicrobial efficacy of the antibiotic hosted within the mesopores. This nanodevice is envisioned as a promising alternative to conventional treatments for infection by improving the antimicrobial efficacy and reducing side effects.Unión Europea. Horizonte 2020Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEinpres

    Amine-Functionalized Mesoporous Silica Nanoparticles: A New Nanoantibiotic for Bone Infection Treatment

    Get PDF
    RESEARCHER ID M-9921-2014 (Isabel Izquierdo Barba) ORCID 0000-0002-4139-4646 (Isabel Izquierdo Barba) RESEARCHER ID N-4628-2014 (Montse Colilla Nieto) ORCID 0000-0003-1961-4160 (Montse Colilla Nieto) RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)This manuscript reports an effective new alternative for the management of bone infection by the 5 development of an antibiotic nanocarrier able to penetrate bacterial biofilm, thus enhancing antimicrobial effectiveness. This nanosystem, also denoted as “nanoantibiotic”, consists in mesoporous silica nanoparticles (MSNs) loaded with an antimicrobial agent (levofloxacin, LEVO) 10 and externally functionalized with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (DAMO) as targeting agent. This amine functionalization provides MSNs of positive charges, which improves the affinity towards the negatively charged bacteria wall and biofilm. Physical and 15 chemical properties of the nanoantibiotic were studied using different characterization techniques, including Xray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption porosimetry, elemental chemical analysis, dynamic light scattering (DLS), zeta (� )-potential 20 and solid-state nuclear magnetic resonance (NMR). “In vial” LEVO release profiles and the in vitro antimicrobial effectiveness of the different released doses were investigated. The efficacy of the nanoantibiotic against a S. aureus biofilm was also determined, showing the practically total 25 destruction of the biofilmdue to the high penetration ability of the developed nanosystem. These findings open up promising expectations in the field of bone infection treatment.Unión Europea. H2020Ministerio de Economía y Competitividad (MINECO)Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEpu

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Get PDF
    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

    Get PDF
    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Scaffold Designing

    No full text
    corecore