Prevention of Bacterial Adhesion to Zwitterionic Biocompatible Mesoporous Glasses

Novel materials, based on Mesoporous Bioactive Glasses(MBGs) in the ternary system SiO2-CaO-P2O5, decorated with (3-aminopropyl)triethoxysilane (APTES) and subsequently with amino acid Lysine (Lys), by post-grafting method on the external surface of the glasses (named MBG-NH2 and MBG-Lys), are reported. The surface functionalization with organic groups did not damage the mesoporous network and their structural and textural properties were also preserved despite the high solubility of MBG matrices. The incorporation of Lys confers a zwitterionic nature to these MBG materials due to the presence of adjacent amine and carboxylic groups in the external surface. At physiologic pH, this coexistence of basic amine and carboxilic acid groups from anchored Lys provided zero surface charge named zwitterionic effect. This behaviour could give rise to potential applications of antibacterial adhesion. Therefore, in order to assess the influence of zwitterionic nature in in vitro bacterial adhesion, studies were carried out with Staphylococcus aureus. It was demonstrated that the efficient interaction of these zwitterionic pairs onto the MBG surfaces reduced bacterial adhesion up to 99.9% compared to bare MBGs. In order to test the suitability of zwitterionic MBGs materials as bone grafts, their cytocompatibility was investigated in vitro with MC3T3-E1 preosteoblasts. These findings suggested that the proposed surface functionalization strategy provided MBG materials with notable antibacterial adhesion properties, hence making these materials promising candidates for local bone infection therapy

Antibacterial effect of 3D printed mesoporous bioactive glass scaffolds doped with metallic silver nanoparticles

The development of new biomaterials for bone tissue regeneration with high bioactivity abilities and antibacterial properties is being intensively investigated. We have synthesized nanocomposites formed by mesoporous bioactive glasses (MBGs) in the ternary SiO2, CaO and P2O5 system doped with metallic silver nanoparticles (AgNPs) that were homogenously embedded in the MBG matrices. Ag/MBG nanocomposites have been directly synthesized and silver species were spontaneously reduced to metallic AgNPs by high temperatures (700ºC) obtained of last MBG synthesis step. Three-dimensional silver-containing mesoporous bioactive glass scaffolds were fabricated showing uniformly interconnected ultrapores, macropores and mesopores. The manufacture method consisted of a combination of a single-step sol-gel route in the mesostructure directing agent (P123) presence and a biomacromolecular polymer such as (hydroxypropyl)methyl cellulose (HPMC) as the macrostructure template, followed by rapid prototyping (RP) technique. Biological properties of Ag/MBG nanocomposites were evaluated by MC3T3-E1 preosteoblastic cells culture tests and bacterial (E. coli and S. aureus) assays. The results showed that the MC3T3-E1 cells morphology was not affected while preosteoblastic proliferation decreased when the presence of silver increased. Antimicrobial assays indicated that bacterial growth inhibition and biofilm destruction were directly proportional to the increased presence of AgNPs in the MBG matrices. Furthermore, in vitro co-culture of MC3T3- E1 cells and S. aureus bacteria confirmed that AgNPs presence was necessary for antibacterial activity, and AgNPs slightly affected cell proliferation parameters. Therefore, 3D printed scaffolds with hierarchical pore structure and high antimicrobial capacity have potential applications in bone tissue regeneration

Design of 3D Scaffolds for Hard Tissue Engineering: From Apatites to Silicon Mesoporous Materials

Advanced bioceramics for bone regeneration constitutes one of the pivotal interest in the multidisciplinar and far-sighted scientific trajectory of Prof. Vallet Regí. The different pathologies that affect osseous tissue substitution are considered to be one of the most important challenges from the health, social and economic point of view. 3D scaffolds based on bioceramics that mimic the composition, environment, microstructure and pore architecture of hard tissues is a consoli16 dated response to such concerns. This review describes not only the different types of materials utilized: from apatites-type to silicon mesoporous materials, but also the fabrication techniques employed to design and adequate microstructure, a hierarchical porosity (from nano to macro scale), a cell-friendly surface; the inclusion of different type of biomolecules, drugs or cells

Proton Environments in Biomimetic Calcium Phosphates Formed from Mesoporous Bioactive CaO-SiO2- P2O5 Glasses in vitro: Insights from Solid-State NMR

When exposed to body fluids, mesoporous bioactive glasses (MBGs) of the CaO{SiO2{P2O5 system develop a bone-bonding surface layer that initially consists of amorphous calcium phosphate(ACP), which transforms into hydroxy-carbonate apatite (HCA) with a very similar composition as bone/dentin mineral. Information from various 1H-based solid-state nuclear magnetic resonance (NMR) experiments were combined to elucidate the evolution of the proton speciations both at the MBG surface and within each ACP/HCA constituent of the biomimetic phosphate layer formed when each of three MBGs with distinct Ca, Si, and P contents was immersed in a simulated body fluid (SBF) for variable periods between 15 min and 30 days. Directly excited magic-angle-spinning (MAS) 1H NMR spectra mainly reflect the MBG component, whose surface is rich in water and silanol (SiOH) moieties. Double-quantum{single-quantum correlation 1H NMR experimentation at fast MAS revealed their interatomic proximities. The comparatively minor H species of each ACP and HCA component were probed selectively by heteronuclear 1H{31P NMR experimentation. The initially prevailing ACP phase comprises H2O and "non-apatitic" HPO2

Effective reduction of biofilm through photothermal therapy by gold core@shell based mesoporous silica nanoparticles.

Bacterial biofilms can initiate chronic infections that become difficult to eradicate. There is an unmet need for effective therapeutic strategies that control and inhibit the growth of these biofilms. Herein, light sensitive mesoporous silica nanoparticles (MSNs) with photothermal (PTT) and antimicrobial combined capabilities have been developed. These nanosystems have high therapeutic potential to affect the bacterial biofilm architecture and subsequently inhibit its growth. Nucleation of gold nanorods followed by the growth of a silica shell leads to a core@shell design (AuNR@MSN) with PTT properties. Incorporation of nitrosothiol groups (-SNO) with a heat liable linker, enables an enhanced nitric oxide release upon photothermal stimulation with near infrared radiation. Further loading of an antimicrobial molecule such as the levofloxacin (LEVO) antibiotic creates a unique nanoassembly with potential therapeutic efficacy against Staphylococcus aureus bacterial biofilms. A dispersion rate of the bacterial biofilm was evident when light stimuli is applied because impregnation of the nitrosothiol functionalized nanosystem with the antibiotic LEVO led to ca. 30% reduction but its illumination with near infrared (NIR) irradiation showed a biofilm reduction of ca. 90%, indicating that localized antimicrobial exposure and PTT improves the therapeutic efficacy. These findings envision the conception of near-infrared-activated nanoparticle carriers capable of combined therapy upon NIR irradiation, which enables photothermal therapy, together with the release of levofloxacin and nitric oxide to disrupt the integrity of bacterial biofilms and achieve a potent antimicrobial therapy

Complete process of implantation of a nutritional risk screening system in the University Hospital La Paz, Madrid

La malnutrición asociada a la enfermedad (MAE) está presente en un porcentaje muy elevado de los pacientes que ingresan en los hospitales y su repercusión es diversa y de mucha trascendencia. Objetivo: Desde la Unidad de Nutrición del Hospital Universitario la Paz, en colaboración con todos los miembros de la Comisión de Nutrición, nos planteamos implantar algún método de cribado en nuestro centro, que permitiese abarcar al mayor número posible de pacientes. Resultados: Debido al gran tamaño de nuestro centro, con cerca de 1500 camas, unido a una escasez de recursos humanos en nuestra unidad, optamos por utilizar el sistema de cribado CONUT (Control Nutricional) 100% automático y basado en parámetros analíticos, muy fácil de manejar, de bajo coste y cuya validez está confirmada, adaptándolo a nuestras necesidades. El método recoge información de las bases de datos del servicio de Admisión (filiación, edad, fecha) y del Laboratorio (albúmina, colesterol, linfocitos totales) y genera, en el informe de resultados de los análisis clínicos, la información sobre la alerta de riesgo nutricional de cada paciente, así como las recomendaciones nutricionales a seguir en función del riesgo detectado en cada caso. Para llegar su implantación se llevaron a cabo diferentes evaluaciones que nos permitieron conocer previamente la carga extra de trabajo que podría generar su implantación y nuestra capacidad para asumirlas, así como numerosas actividades formativas encaminadas a que los médicos y profesionales sanitarios del hospital asumieran cada vez más responsabilidades en el proceso del tratamiento nutricional de sus pacientes. Este sistema de cribado funciona desde Junio del año 2010 y detecta riesgo de desnutrición en el 32% de los pacientes evaluados. En general, sólo en los casos en los que la alerta corresponde a una situación de Alto riesgo nutricional, hecho que se da aproximadamente en el 10% del total, se requirió la intervención especializada por parte de la Unidad de Nutrición Clínica y Dietética. Posteriormente, conforme hemos ido detectando posibles causas que justificaran que el sistema no funcionase adecuadamente, el sistema de cribado ha sido objeto de diversas modificaciones. En este sentido, se ha realizado una evaluación retrospectiva en 233 pacientes ingresados en las plantas de Cirugía General y se ha documentado que aquellos que ingresan para cirugía programada y presentan una alarma alta o moderada de desnutrición (el 50% de los casos), la presencia de la misma aumenta significativamente los días de ingreso y la mortalidad. Conclusiones: La implantación del cribado nutricional ha favorecido un cambio en la cultura de nuestro centro con respecto a la malnutrición asociada a la enfermedad y la mayoría de nuestros profesionales, tanto médicos como enfermeras e incluso el equipo directivo, comprenden la importancia del proceso y saben que disponemos de herramientas y de conocimiento suficiente para indicar un soporte nutricional adecuado y precozDisease-Related Malnutrition (DRM) is present in a high percentage of patients admitted to hospital and their impact is diverse and of great importance. Objectives: Nutrition Department of University Hospital La Paz, in collaboration with all members of the Nutrition Committee, we decided to implement some method of screening in our centre which allowed us to detect as many patients with malnutrition risk as possible. Results: Due to the large size of our centre, with about 1,500 beds and the few human resources in our unit, we chose to use the CONUT system (Nutritional Control), a 100% automatic method based on analytical parameters, very easy to use, low cost and whose validity is confirmed, characteristics that fulfilled our needs. The method collects information from databases of Admission Service (affiliation, age, date) and Laboratory (albumin, cholesterol, total lymphocytes) and generates, in the report of analytical results, “alert” information about each patient’s nutritional risk and also nutritional recommendations based on the risk identified. Prior to its implantation several evaluations were performed in order to allow us to better know the extra workload, as it was the main factor that could limit our ability to assume that screening method and also many training activities for doctors and hospital health professionals who were increasingly assuming responsibilities in the nutritional treatment of their patients. This screening system has been working from june of 2010 and it has detected risk of malnutrition in 32% of the evaluated patients. In general, only in those cases where the alert corresponded to a high-risk nutritional situation, which represents approximately 10% of the total, specialized intervention by the Clinical Nutrition Unit was required. Later, as we have detected some possible causes that justify the system does not work properly; the screening system has undergone several changes . In this sense, we have made a retrospective evaluation of 233 patients admitted to the General Surgery plants and documented that those entering for scheduled surgery, having a alarm of malnutrition (50% of cases), its presence increases significantly the hospital stay and mortality. Conclusions: The implementation of this nutritional screening method has led to a change in the ìnutritionalî culture of our centre respect to DRM in most of our professionals: doctors and nurses and even in the management team, so all of them understand the importance of the process and know about the available tools and knowledge to indicate an adequate and early nutritional suppor

Aprendizaje autónomo del Laboratorio de Química Inorgánica mediante el uso de TICs

Se ha creado un Entorno Virtual de Enseñanza y Aprendizaje (EVEA) circunscrito a la realización de prácticas en el Laboratorio de Química Inorgánica orientado a incrementar el grado de interacción entre el alumno con algún tipo de dificultad auditiva o dificultad idiomática y el profesor o el resto de sus compañeros mediante el uso conjunto del material elaborado y el uso de sistemas basados en redes sociales, mensajerías

Amino functionalized mesoporous silica nanoparticles encapsulated octahedral organoruthenium complex as an efficient platform for combatting cáncer.

In the process of synthesis of a new drug, as important as the drug itself is the formulation used, because the same compound can present a very different efficacy depending on how it is administered. In this work, we demonstrate how the antitumor capacity of a new octahedral organo-ruthenium complex, [Ru(ppy-CHO)(phen)2][PF6] is affected by its encapsulation in different types of mesoporous silica nanoparticles. The interactions between the Ru complex and the silica matrix and how these interactions are affected at two different pHs (7.4 and 5.4, mimicking physiological and endolysosomal acidic conditions, respectively) have been studied. The encapsulation has also been shown to affect the induction of apoptosis and necrosis and progression of the cell cycle compared to the free drug. The encapsulation of the Ru complex in nanoparticles functionalized with amino groups produced very high anticancer activity in cancer cells in vitro, especially against U87 glioblastoma cells, favoring cellular internalization and significantly increasing the anticancer capacity of the initial non-encapsulated Ru complex

Herramientas de Aprendizaje para el Diseño 3D de Estructuras y Procesos Químicos mediante Programas Informáticos Gratuitos/Libres

El objetivo propuesto en este proyecto de innovación docente fue el diseño, elaboración y evaluación de videos tutoriales on-line sobre el manejo de programas informáticos libres/gratuitos para el dibujo de moléculas químicas de interés farmacéutico, nomenclatura, cálculo de fórmulas y el diseño espacial de estructuras tridimensionales, que permitan que el alumno del Grado en Farmacia aprenda el manejo de programas siendo este un apoyo para la realización de su TFG y la defensa de mismo (Póster). Por otro lado, también se planteó el facilitar y animar a que los alumnos de cuarto y quinto curso del Grado en Farmacia presenten comunicaciones en el Congreso de Investigación para Estudiantes Pregraduados de Ciencias de la Salud celebrado todos los años en la UCM