Temperature induced structural changes in even-odd nylons with long polymethylene segments

Structural transitions of nylons 8 9 and 12 9 heating and cooling processes were investigated using calorimetric, spectroscopic during and real time X-ray diffraction data. These even-odd nylons had three polymorphic forms related to structures where hydrogen bonds were established in two planar directions. Heating processes showed a first structural transition at low temperature where the two strong reflections related to the packing mode of the low temperature structure (form I) disappeared instead of moving together and merging into a single reflection, as observed for conventional even-even nylons. The high temperature structure corresponded to a typical pseudohexagonal packing (form III) attained after the named Brill transition temperature. Structural transitions were not completely reversible since an intermediate structure (form II) became clearly predominant at room temperature in subsequent cooling processes. A single spherulitic morphology with negative birefringence and a flat-on edge-on lamellar disposition was obtained when the two studied polyamides crystallized from the melt state. Kinetic analyses indicated that both nylons crystallized according to a single regime and a thermal nucleation. Results also pointed out a secondary nucleation constant for nylon 12 9 higher than that for nylon 8 9, suggesting greater difficulty in crystallizing when the amide content decreased. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 2494–2506Peer ReviewedPostprint (author's final draft

Preparation of medicated polylactide micropieces by means of ultrasonic technology

A technology based on the application of ultrasound as an energy source was applied to get polylactide (PLA) micropieces with minimum degradation and processing time. This requirement could be even shorter than 1.5 s. The ultrasound technology was also demonstrated to be efficient for the incorporation of drugs with a pharmacological activity. Thus, the loading of two representative bactericide agents (i.e., triclosan (TCS), and chlorhexidine (CHX)), having differentiated chemical properties was evaluated. Typical physicochemical characterization included mechanical and thermal properties together with the evaluation of molecular degradation during processing for both unloaded and loaded specimens. Results pointed out that the thermally stable TCS could be loaded into the specimens without any problem, but cautions should be taken into account for CHX. Nevertheless, degradation could in this case be avoided when the drug load was lower than 3 wt-%, a result that contrasts with the significant decomposition attained by using conventional melting processes, which required long processing times at high temperatures. Morphologic analyses of loaded specimens did not reveal significant defects, while spectroscopic analyses showed that a good dispersion of drugs inside pieces could be attained. Drugs were slowly released from micropieces with a rate that was dependent on their hydrophilic character. Thus, release in a phosphate buffered saline (PBS)-ethanol medium (70% of PBS) followed a first order kinetics with constants of 0.0356 h-1 and 0.027 h-1 for CHX and TCS, respectively. A clear bactericide effect against both Gram-positive and Gram-negative bacteria was achieved at the beginning of exposure to the corresponding culture media, while a bacteriostatic effect was interestingly still detected after long exposure times. In fact, bacterial growth could be reduced to near 20% when micropieces were loaded with only 3 wt-% of any of the selected CHX and TCS drugsPostprint (published version

Biodegradable polylactides scaffolds with pharmacological activity by means of ultrasound micromolding technology

Ultrasound micromolding technology has been applied to get microporous polylactide scaffolds from the subsequent leaching of incorporated NaCl salts. A small amount of water-soluble polyethylene glycol (PEG) was required in order to improve the leaching process and get compact pieces with interconnected pores. Distribution of polymers in the processed specimens was quite homogeneous due to the small PEG content, although it was more concentrated in the regions close to the feeding channels due to its higher viscosity. Hydrophobic drugs like triclosan could be incorporated causing a minimum degradation during ultrasound processing and suffering an insignificant solubilization during the leaching step. Final scaffolds showed clear bactericide or bacteriostatic effects before and after 10 h of exposure. Cell proliferation of MDCK epithelial cells was higher for TCS loaded porous scaffolds (200%) than for unloaded samples (170%) and non-porous polylactide (PLA) specimens (100%, control). Micrographs showed the absence of non-inhibition areas in both the specimens and the container, confirming the biocompatibility of PLA specimensPeer ReviewedPostprint (published version

Ultrasound micromolding technique and real-time X-ray diffraction using synchrotron radiation : applications to porous scaffolds for biomedical devices and study of thermal-induced transitions

Current market trend is moving to miniaturized specimens, especially in the biomedical field seeking high effective and less invasive treatrnent. Ultrasound (US) micromolding is a new technique developed to the aim of producing microsized pieces based on the use of ultrasound waves as a heating source. This heating method is highly precise and can lead to produce microsized pieces with high energy and material efficiencies by using short cycling times compared to other conventional techniques. This PhD work explores further possibilities of ultrasound micromolding to the production of polymers with added value. The work is divided in two main blocks: the production of micropieces based on biodegradable polymers focused on biomedical applications and the application of this technique as a new method to obtain nanocomposites with a homogenous dispersion ofthe reinforcing material. Polylactide (PLA) was selected as polymer matrix in the first block to produce drug loaded pieces and scaffolds with antibacterial activity or increased osteoconductivity by the incorporation of hydroxyapatite (HAp). Chlorhexidine (CHX) and triclosan (TCS), selected as representative bactericide agents, were successfully loaded with a homogenous distribution into the polymer matrix Drugs were slowly released from micropieces and presented clear bactericide and bacteriostatic effect against both Gram-positive and Gram-negative bacteria. Microporous scaffolds have been produced from the subsequent leaching of incorporated salts. By using NaCI cavitation problems could be avoided but pores interconnections were insufficient anda small amount of water soluble polymer (i.e. polyethylene glycol) was required in order to improve the leaching process. Final scaffolds showed enhanced cell proliferation compared to non-porous PLA PLNHAp scaffolds with a porosity degree close to 35% could be achieved with relatively good mechanical properties. lncorporation of HAp increased the thermal stability, hydrophilicity and cell proliferation with respect to neat PLA specimens. Ultrasound waves are usuallycombined with the conventional method to produce nanocomposite (i.e. solution intercalation and melt mixing) to avoid nanoparticles aggregation and improve their distribution within the polymer matrix Hence the second block ofthis PhD work studies the use of ultrasound micromolding technology in nanocomposites production. To this end, Polycaprolactone and polyamide 12 were selected as polymer matrices whereas multi-walled carbon nanotubes (MWCNT) and Nanofil 757 (a non-organo modified clay) were chosen as reinforcing agent. Both neat polymers and their nanocom posites were successfully micromolded with minimal polymer degradation under optimal molding condition (amplitude, force and time). US micromolding technique was revealed to be efficient in getting fully exfoliated nanocomposites even when Nanofil 757 was selected. Moreover, the influence of both, MWCNTand Nanofil 757, on crystallization behaviorand morphology were systematically studied by time resolved synchrotron experiments. Crystalline polymorphic transitions of nylon 12 were also evaluated through analyses of real time synchrotron. A final chapter of this thesis is devoted to the study of structural transitions of nylons 12 9, 8 9, 4 9, 4 5 and copolymers derived from 1,4-diam inobutane and different ratios of glutaric and azelaic acids (nylon 4, 5+9) in order to achieve deeper knowledge on the series of even-odd polyam ides. These polyamides show different crystalline structure and structural transitions compared to the conventional polyamides, which root cause is still unclear.El uso de piezas de tamaño reducido se ha extendido en los últimos años como sinónimo de evolución tecnológica, especialmente en biomedicina, donde se están realizando grandes avances con el fin de mejorar la eficiencia de los tratamientos terapéuticos y aumentar el uso de procedimientos menos invasivos. El micromoldeo por ultrasonidos (USM) es una novedosa técnica para la obtención de micropiezas caracterizada por el uso de ultrasonidos como fuente de calor; gracias a este sistema calefacción el USM presenta tiempos de ciclo extremadamente cortos y un alto rendimiento energético. El trabajo expuesto en esta tesis doctoral se divide en dos partes, un primer bloque enfocado en explorar posibles aplicaciones biomédicas de micropiezas basadas en polímeros biodegradables y un segundo bloque en el que se estudia la posibilidad del uso de dicha técnica para la preparación de nanocompuestos. La polilactida (PLA) fue seleccionada como polímero biodegradable en el primer bloque para la producción de micropiezas cargadas con fármacos y scaffolds con actividad antibacteriana o reforzada con hidroxiapatita (HAp) para incrementar su osteoconductividad. Como agentes bactericidas se escogieron clorhexidina (CHX) y triclosan (TCS), los cuales se cargaron con éxito en la matriz de PLA presentando una distribución uniforme y una clara actividad antibacteriana. Los scaffolds porosos se prepararon por un proceso indirecto al remover la sal soluble en agua tras ser moldeada junto al polímero. Aunque era factible obtener piezas de PLA cargadas con NaCI sin problemas de cavitación o degradación del polímero la conexión entre los poros era insuficiente y una gran cantidad de sal quedaba retenida en la pieza final. Con tal de incrementar dicha interconexión y conseguir un scaffolds poroso libre de NaCI fue necesario agregar polietilenglicol (PEG). Los scaffolds finales cargados con TCS presentan una mejora en la proliferación celular, un efecto bactericida y bacteriostático y una liberación más rápida. En los sistemas PLA/HAp fue crítico el uso HAp libre de impurezas para evitar cavitaciones yamarilleamiento en las muestras. La incorporación de HAp mejoró la estabilidad térmica, la hidrofobicidad y la proliferación y colonización celular. Los procesos convencionales para la producción de nanocompuestos (preparación por disolución y mezclado en fundido) suelen usar ondas de ultrasonidos para mejorar el proceso y evitar la aglomeración de las nanopartículas, aumentando así las interacciones refuerzo-polímero. Con esta premisa en mente el segundo bloque de esta tesis abarca la producción, mediante USM de dos tipos de nanocom puestos: una matriz de policaprolactona (PCL) con nanotubos de carbono (MWCNT) y una matriz de poliamida 12 (Nylon 12) con arcilla. El USM es un proceso adecuado para la obtención de nanocompuestos exfoliados en un solo paso, incluso cuando la arcilla utilizada no ha sido modificada orgánicamente (N757). La influencia de ambos agentes externos (MWCNT y N757) en el proceso de cristalización y la morfología cristalina se han estudiado mediante e>IJ) erimentos de sincrotrón en tiempo real. Las transiciones polimórficas del nylon 12 también fueron estudiadas mediante los datos recopilados en los experimentos con radiación sincrotrón. En un último bloque se han estudiado también las estructuras y transiciones estructurales de los nylons 12 9, 8 9, 4 9, 4 5, así como varias copoliamides derivadas de la 1,4-butanodiamina y distintas proporciones de ácidos glutárico y azelaico (nylon 4,5+9) mediante datos calorimétricos, espectrocópicos y de difracción de rayos X recogidos en barridos de calentamiento y enfriamiento . Estas poliamidas tipo par-impar muestran estructuras peculiares y unas transiciones estructurales diferentes a las de otras poliamidas convencionales y cuyo origen aún no está claro.Postprint (published version

Micromoldeo por ultrasonidos de ácido poliláctico: Preparación de nanocompuestos y carga con fármacos

En este proyecto se ha trabajado con una novedosa técnica de moldeo, basada en el uso energía de ultrasonidos. Éste equipo de moldeo nace de la necesidad de obtener una técnica de moldeo de micro piezas más eficiente; sobre todo en el campo de la medicina y electrónica. En anteriores trabajos se ha demostrado la viabilidad de esta técnica para moldear micro piezas ofreciendo grandes ventajas sobre el resto de técnicas de micro-moldeo. Es por ello que en el presente trabajo se ha estudiado la posibilidad de producir micropiezas con un valor añadido. En concreto, piezas de polímero cargadas con agentes antibacterianos y por otra parte la incorporación de arcillas para formar nanocompuestos. El polímero escogido como matriz es la poliláctida (PLA) debido a su biocompatibilidad, su biodegradabilidad y la capacidad de obtenerse a partir de fuentes renovables. En una etapa previa del proyecto se han determinado las condiciones adecuadas de moldeo para la PLA: fuerza, amplitud y tiempo. Las condiciones se analizan según: un correcto llenado del molde, una mínima degradación del polímero, la ausencia de microfisuras derivadas de fenómenos de cavitación, el mantenimiento o mejora de las propiedades mecánicas y térmicas de las piezas. La caracterización se realiza mediante cromatografía de permeación en gel (GPC), espectrofotometría infrarroja (FTIR), ensayos mecánicos, microscopia electrónica de barrido (SEM) y calorimetría diferencial de barrido (DSC). Se ha demostrado la viabilidad de esta técnica para la obtención de nanocompuestos derivados de arcillas tanto sin modificar o modificadas con un agente orgánico que actúe como compatibilizador. Los ensayos de difracción de rayos X y la observación directa de las piezas mediante microscopia electrónica de transmisión (TEM) permitieron concluir que las láminas de las arcillas se encontraban totalmente separadas entre sí, nanocompuesto exfoliado, por lo que esta técnica presenta grandes ventajas frente a otros métodos de obtención de nanocompuestos gracias a su sencillez y a la posibilidad de obtener los nanocompuestos directamente en la forma final de la pieza y con una estructura exfoliada que es la que presenta unas mayores ventajas. También se ha estudiado como afecta la incorporación de arcillas a la cristalización de la PLA, en este sentido se han realizado dos ensayos: estudio de cristalización no isotérmica empleando la calorimetría diferencial de barrido (DSC) y un estudio de cristalización isotérmico mediante microscopia óptica. Ambos estudios han permitido concluir que la nucleación se ve claramente afectada por la presencia de arcillas, observándose en concreto que la arcilla C25A produce un peculiar efecto anti-nucleante al reducirse el número de núcleos y ralentizarse el proceso global de cristalización. Los fármacos cargados en el polímero han sido el triclosan y la clorhexidina, ambos son potentes agentes antibacterianos. Se ha podido comprobar que la actividad biológica del fármaco no ha sido alterada por la acción de los ultrasonidos y que las piezas obtenidas presentan una distribución uniforme del fármaco dentro de la matriz. Sin embargo, en el caso de la clorhexidina la carga no puede ser demasiado elevada, por debajo de un 2-3%, si quiere evitarse una pérdida significativa de las propiedades mecánicas del polímero causada por una degradación acelerada por la presencia de clorhexidina. Los ensayos de liberación y estudio de carga han sido evaluados mediante espectroscopia UV-visible, mientras que los ensayos biológicos se han efectuado utilizando las líneas celulares Escherichia coli y Staphylococcus epidermidis

Ultrasound micromolding of porous polylactide/hydroxyapatite scaffolds

Ultrasound micromolding (USM) preparation of hybrid scaffolds based on polylactide (PLA) and hydroxyapatite (HAp) particles has been evaluated. PLA was stable under the applied ultrasound source since a minimum degradation was detected. Porous materials were achieved using polyethylene glycol (PEG) and NaCl salts to the initial PLA and the subsequent leaching of the micromolded specimens. To avoid cavitation and decomposition problems during micromolding, it was necessary to use HAp free of typical synthesis impurities like carbonate and nitrate compounds. Compact PLA/HAp pieces allowed a maximum HAp load of 60 wt%, while porous specimens could be obtained with a maximum load of 38 wt%. Physical characterization of new scaffolds was performed by X-ray diffraction, spectroscopic and calorimetric techniques, stress-strain tests and contact angle measurements. Results indicated that a degree of porosity of 35% and relatively good mechanical properties could be achieved (i.e., 580 MPa, 4%, and 15.6 MPa for the Young modulus, elongation at break, and tensile strength, respectively). Scaffolds showed the positive effect of HAp and porosity on cell proliferation; this latter was 40% higher than that detected for non-porous PLA specimens.Peer ReviewedPostprint (published version

Temperature induced structural changes in even-odd nylons with long polymethylene segments

Structural transitions of nylons 8 9 and 12 9 heating and cooling processes were investigated using calorimetric, spectroscopic during and real time X-ray diffraction data. These even-odd nylons had three polymorphic forms related to structures where hydrogen bonds were established in two planar directions. Heating processes showed a first structural transition at low temperature where the two strong reflections related to the packing mode of the low temperature structure (form I) disappeared instead of moving together and merging into a single reflection, as observed for conventional even-even nylons. The high temperature structure corresponded to a typical pseudohexagonal packing (form III) attained after the named Brill transition temperature. Structural transitions were not completely reversible since an intermediate structure (form II) became clearly predominant at room temperature in subsequent cooling processes. A single spherulitic morphology with negative birefringence and a flat-on edge-on lamellar disposition was obtained when the two studied polyamides crystallized from the melt state. Kinetic analyses indicated that both nylons crystallized according to a single regime and a thermal nucleation. Results also pointed out a secondary nucleation constant for nylon 12 9 higher than that for nylon 8 9, suggesting greater difficulty in crystallizing when the amide content decreased. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016, 54, 2494–2506Peer Reviewe

Thermally induced structural transitions of nylon 4 9 as a new example of even-odd polyamides

Crystalline morphology and structure of nylon 4 9 have been studied by means of optical and transmission electron microscopies, and X-ray diffraction. Rhombic crystals were characteristic of crystallization from glycerin dilute solutions, although the final morphology was dependent on the crystallization temperature. In any case, a single electron diffraction pattern was always obtained, being characteristic a 2 mm symmetry and reflections at spacings that were indicative of a projected rectangular unit cell with hydrogen bonds established along two planar directions (i.e., the diagonals of the unit cell), as it was determined from related polyamides. Crystallization from the melt gave rise to negative birefringent spherulites with a morphology (axialitic, speckled or ringed) that was dependent on the crystallization temperature. Kinetic analysis indicated that melt crystallization took place according to two growth mechanisms (Regimes II and III), which reflect distinct secondary nucleation rates. A complex polymorphic behavior on heating and cooling processes was evidenced by real time synchrotron experiments, being determined an intermediate crystalline structure as well as the typical pseudohexagonal arrangement associated to the Brill transition. Polymorphic transitions were highly dependent on the initial crystalline structure, being enhanced the structural transition from the low temperature structure to the intermediate one when traces of the latter were initially present. Calorimetric and infrared studies supported also the detected thermal transitions of nylon 4 9.Peer Reviewe

Preparation of nanocomposites of poly(epsilon-caprolactone) and multi-walled carbon nanotubes by ultrasound micro-molding. Influence of nanotubes on melting and crystallization

Ultrasound micro-molding technology was successfully applied to prepare nanocomposites based on a poly(e-caprolactone) (PCL) matrix and multi-walled carbon nanotubes (MWCNTs). Optimization of processing parameters (i.e. amplitude, force and time) was crucial to obtain nanocomposites without any evidence of degradation, high material saving and short processing time (7–8 s). Good dispersion of nanotubes was achieved after processing previously formed solvent casting films. This dispersion was even partially detected in pieces directly obtained from powder mixtures of both components. Incorporation of MWCNTs had a remarkable influence on melting and crystallization processes, which were systematically studied by time resolved synchrotron experiments. Results indicated higher melting and crystallization temperatures for the nanocomposite, with temperature differences higher than 5 °C. Carbon nanotubes were effective nucleating agents and had an influence on crystallinity, crystallization rate and even on lamellar morphology, which was evaluated by analysis of the correlation function of small angle diffraction profiles. Crystallinity within lamellar stacks was lower for the solvent casting nanocomposite, but in this case lamellae underwent a thickening process during heating that accounted for the increase in the melting temperature. Crystallization from the melt rendered similar lamellar morphologies at the end of the process due to a lamellar insertion mechanism.Peer Reviewe

Preparation of micro-molded exfoliated clay nanocomposites by means of ultrasonic technology

Ultrasound micro-molding technology has been tested as a new method to get polymer/clay nanocomposites. Biodegradable polylactide (PLA) and poly (nona-methylene azelate) (PE99) have been used as polymer matrices, whereas different silicate clays have been assayed. The new technology is able to get specimens without evidences of degradation during processing. Only the use of organo-modified clays could give rise to a slight molecular weight decrease when the poly (alkylene dicarboxylate) sample was considered. Ultrasonic micro-molding has revealed effective to get directly nanocomposites with the final form required for a selected application, a homogeneous clay distribution up to a load of 6 wt-% and more interestingly exfoliated structures without being necessary the use of a compatibilizer agent between the organic polymer and the inorganic silicate clay. Transmission electron micrographs and X-ray diffraction profiles revealed exfoliated structure when N757, C20A, C25A, and N848 clays were employed.; Crystallization behavior of exfoliated PLA nanocomposites was highly peculiar since clay particles had an antinucleating effect that decreased the overall crystallization rate respect to the neat polymer. In addition, the incorporation of layers into growing spherulites increased the crystal growth rate. A typical crystallization effect was on the contrary observed for nanocomposites derived from the poly (alkylene dicarboxylate) sample.Peer ReviewedPostprint (published version