L’objectif de ce travail a été de procéder au design de nouvelles structures hyperramifiées en procédant à la synthèse de polymères à base de glycidol utilisables dans l’élaboration de copolymères biodégradables, de macromonomères fonctionnels et de nanocomposites magnétiques biocompatibles. Une première partie de ces travaux s’est intéressée, à la synthèse de macromonomères hyperramifiés amorcés par l’hydroxyéthyle méthacrylate (HEMA), l’hydroxyéthyle acrylate (HEA) et le polyéthylène glycol méthacrylate (PEGMA), par polymérisation anionique, anionique coordinée ou cationique du glycidol. La synthèse de macromonomères poly(ε-caprolactone) en présence de différents systèmes catalytiques et amorceurs a également été investiguée. Cette partie se termine par la synthèse de dendrigrafts issus de la polymérisation de ces macromonomères, par voie radicalaire classique ou contrôlée (RAFT/ATRP). La seconde partie de ce travail a été consacrée à la synthèse de copolymères hyperramifiés biocompatibles obtenus par copolymérisation statistique du glycidol en présence d’ε-caprolactone, en vu de l’obtention de copolymères hydrolysables. L’impact de la structure sur les propriétés physico-chimiques des copolymères obtenus a été étudié. Enfin, le caractère biodégradable de ces polymères a été investigué à travers différents tests de dégradation enzymatique. Enfin, ce travail s’est focalisé sur l’élaboration de nanocomposites magnétiques biocompatibles par la synthèse de nanoparticules magnétiques, puis l’immobilisation de polymères linéaires ou hyperramifiés à leur surface selon différentes méthodes de greffage chimique. / The aim of this work was to proceed to the design of new hyperbranched structures through the synthesis of glycidol-based polymers which can be used in the development of biodegradable copolymers, functional macromonomers and biocompatible magnetic nanocomposites. The first part of this work was the synthesis of hyperbranched macromonomer initiated by hydroxyethyl methacrylate (HEMA), hydroxyethyl acrylate (HEA) and polyethylene glycol methacrylate (PEGMA), through the study of the synthesis of polyglycerol (PG) by anionic, anionic coordinated and cationic polymerization of glycidol. Synthesis of poly (ε-caprolactone) macromonomers in the presence of various catalyst systems and initiators was also investigated. This part ends by the synthesis of dendrigrafts derived from the copolymerization of the macromonomers, by free radical polymerization or by controlled radical polymerization. The 2nd part of this work has been devoted to the synthesis of hyperbranched biocompatible copolymers obtained by random copolymerization of glycidol with ε-caprolactone in order to obtain hydrolyzable copolymers. The impact of the structure of the copolymers on their physico-chemical properties was then investigated. The biodegradable behavior of these polymers was then investigated through different enzymatic degradation tests. Finally, this work was focused on the development of biocompatible magnetic nanocomposites by the synthesis of magnetic nanoparticles and the immobilization of linear or hyperbranched polymers on their surface by different chemical grafting methods.

This thesis is an experimental investigation of the phase behavior, volumetric properties, and viscosity of poly (methyl methacrylate) (PMMA), poly (ε-caprolactone) (PCL) and their blends. Homopolymerization and copolymerizations of methyl methacrylate (MMA) and 2-methylene-1,3-dioxepane (MDO) in mixtures of acetone + CO2 have also been explored. The viscosities and densities of acetone + CO2 mixtures were measured in the temperature range 323-398 K at pressures up to 35 MPa. This is the first study in which viscosity of acetone + CO2 mixtures have been measured and the mixtures have been evaluated as solvents for PCL. It is shown that PCL can be readily dissolved in these fluid mixtures at modest pressures even at high carbon dioxide levels. Investigations have been conducted over a temperature range from 323 to 398 K at pressures up to 50 MPa for polymer concentrations up to 20 wt %, and CO2 concentrations up to 60 wt %. It is shown that in these mixtures PCL is dissolved at pressures that are much lower than the pressures reported for miscibility in the mixtures of carbon dioxide with other organic solvents. It is shown that PMMA also readily dissolves at modest pressures. Blends of PMMA and PCL require higher pressures than for the individual polymers for complete miscibility. Free-radical polymerizations of MMA in acetone at 343 K were followed using in-situ measurements of viscosity and density at different pressures from 7- 42 MPa. This is the first time viscosity has been used as a real-time probe of high pressure polymerizations. Two distinct kinetic regimes were identified. Homopolymerizations of MDO were conducted in carbon dioxide at 323 and 343 K at pressures up to 42 MPa. For the first time it is shown that high molecular weight PCL can be produced from MDO in high pressure CO2. Ring-opening free-radical copolymerizations of MDO with MMA, styrene and acrylonitrile were conducted for the first time in carbon dioxide and have been shown to lead to polymers with high molecular weights. / Ph. D.

Ce travail présente la synthèse de ligands mixtes germylène-sulfoxyde qui ont été utilisés en chimie de coordination avec plusieurs métaux de transitions et finalement appliqués en catalyse de transfert d'hydrogène. Une seconde partie de ce travail est axée sur la synthèse de nouveaux métallylènes stabilisés par un sulfonimidamide qui ont été appliqués en catalyse de polymérisation. Le premier chapitre présente l'état de l'art des germylènes avec leurs synthèses, modes de stabilisations et finalement leur chimie de coordination et leurs applications en catalyse. Les sulfoxydes seront aussi décrits pour leur application en tant que ligands hémilabiles. Le second chapitre décrit la synthèse de ligands germylène-α-sulfoxide avec une diversité structurale (cyclohexyle, tBu, tolyle..) et avec différents degrés d'oxydation du souffre (thioéther, sulfoxyde et sulfone). La chimie de coordination a permis la synthèse de complexes bis-germylène du groupe IV, bidentes du ruthénium ainsi que monodentes du ruthénium. Le troisième chapitre présente l'extension de la méthodologie à la formation de ligands germylène-β-sulfoxide. L'influence du groupement espaçant les deux entités sur la chimie de coordination a été étudiée et montre la formation de complexes bidentates du groupe IV. La coordination du ruthénium a mené à la surprenante synthèse d'un complexe bis-ruthénium caractérisé par diffraction des rayons X. Finalement, la nouvelle architecture a permis d'obtenir des complexes de nickel (0) dont une structure avec des ligands carbonyles permettant une comparaison TEP. Le chapitre quatre présente la synthèse de nouveaux ligands, analogues des amidinates, pour la stabilisation des métallylènes avec un atome central soufré. L'effet apporté sur les métallylènes par ces nouveaux ligands sulfonimidamides a été étudié par calcul DFT. Le dernier chapitre est centré sur l'application de plusieurs complexes de ruthénium en catalyse de transfert d'hydrogène avec plusieurs substrats carbonylés. L'utilisation de stannylènes stabilisés par des ligands sulfonimidamides a été étudiée en catalyse de polymérisation de la ε-caprolactone. / This work concerns the synthesis of mixed germylene-sulfoxide ligands that were involved in coordination chemistry with several transition metals and finally applied in hydrogen transfer catalysis. In a second part, the synthesis of new metallylenes stabilized by a sulfonimidamide group was develop, which were applied in polymerization catalysis. The first chapter is centered on the state of the art of germylenes with their synthesis, their stabilization and finally their coordination chemistry and applications in catalysis. Sulfoxides will also be described for their potential as hemilabile ligands. The second chapter describes the synthesis of germylene-α-sulfoxide ligands as structurally tunable structures (cyclohexyl, tBu, tolyl..) and with different oxidation states of the sulfur atom (thioether, sulfoxide and sulfone). The coordination chemistry led to the formation of bis-germylene group IV complexes, bidentate-ruthenium and monodentate ruthenium complexes. The third chapter shows the extension of the methodology to the formation of germylene-β-sulfoxide ligands. The influence of the spacer between the two entities on the coordination chemistry was studied and shows the formation of bidentate group IV complexes. Coordination to ruthenium led to obtain a surprising bis-ruthenium complex characterized by X-ray diffraction analysis. Finally, the novel architecture allowed to obtain two nickel (0) complexes, one of them including carbonyl ligands permitting a TEP comparison. The fourth chapter is centered on the synthesis of new ligands, analogue of amidinate substituents for metallylene stabilization with a central sulfur atom. The effect brought to the metallylene center by the sulfonimidamide was studied by DFT calculations. The last chapter concerns the application of several ruthenium complexes in hydrogen transfer reaction with various carbonyl compounds. The use of sulfonimidamide stannylenes was also investigated in polymerization catalysis of ε-caprolactone.

Chitosan, Whey Protein Isolate (WPI) and vital wheat gluten (WG) are three biomaterials that have quite promising properties for packaging purposes. They have good film forming properties and good gas barrier properties in dry conditions. Moreover, because they are produced from industrial waste of food processing, they offer an ecological advantage over polymers made from petroleum. However, their physicochemical characteristics still must be improved for them to be of commercial interest for the food packaging industry. The purpose of this work was to study different strategies aiming to improve the water resistance and aging properties of these polymers, which are some of the key disadvantages of these materials. The produced solution cast chitosan and WPI films were characterised with scanning electron microscopy (SEM), density measurements and thermogravimetry. The water vapour transmission rate was determined at a relative humidity of 11%. In the first part, mechanical properties of solid films and seals were assessed by tensile testing. WG film’s tensile properties and oxygen and water vapour permeabilities were measured as a function of aging time. The changes in the protein structure were determined by infrared spectroscopy and size-exclusion high-performance liquid chromatography and the film structure was revealed by optical and scanning electron microscopy. Gluten-clay nanocomposites were characterised by tensile testing, X-ray diffraction and transmission electron microscopy. The incorporation of a hydrophobic biodegradable polymer, poly ( ε-caprolactone), PCL, in both chitosan and whey protein, yielded a significant decrease in water vapour transmission rate. It was observed that a certain amount of the PCL particles were ellipsoidal in chitosan and fibrous in WPI. The obtained data also indicated that the particle shape had an important influence in the water vapour transmission rate. In the second part, the aging properties of WG films, plasticized with glycerol and cast from water/ethanol solutions with pH=4 or pH=11 were investigated. WG films made from alkaline solutions were mechanically more time-stable than the acidic ones, the latter being initially very ductile but turning brittle towards the end of the aging period. The protein solubility measurements indicated that the protein structure of the acidic films was initially significantly less aggregated than the in basic films. During aging the acidic films lost more mass than the basic films through slow evaporation of volatiles (water/ethanol) and through migration of glycerol to the paper support. The oxygen permeability was also lower for the basic films. In the last part, the properties of new and aged glycerol-plasticized WG films at acidic and basic conditions containing ≤4.5 wt% natural or quaternary-ammonium-salt-modified montmorillonite were studied. Films of WG with montmorillonite were possible to produce by solution casting. The aging rate of acidic and basic films was unaffected by the incorporation of clay. However, the large reduction in water vapour permeability for most systems suggested that the clay sheets were evenly distributed within the films. The film prepared from basic solution and containing natural clay was almost completely exfoliated as revealed by transmission electron microscopy and X-ray diffraction. The best water vapour barrier properties were obtained by using modified clay. / QC 20101013

<p>The use of synthetic materials for tissue and organ reconstruction, i. e. tissue engineering, has become a promising alternative to current surgical therapies and may overcome the shortcomings of the methods in use today. The challenge is in the design and reproducible fabrication of biocompatible and bioresorbable polymers, with suitable surface chemistry, desirable mechanical properties, and the wanted degradation profile. These material properties can be achieved in various manners, including the synthesis of homo- and copolymers along with linear and star-shaped architectures. In many applications the materials’ three-dimensional structure is almost as important as its composition and porous scaffolds with high porosity and interconnected pores that facilitate the in-growth of cells and transportation of nutrients and metabolic waste is desired.</p><p>In this work linear and star-shaped polymers have been synthesized by ring-opening polymerization using a stannous-based catalyst and a spirocyclic tin initiator. A series of linear copolymers with various combinations of 1,5-dioxepane-2-one (DXO), Llactide (LLA) and ε-caprolactone (CL) have been polymerized using stannous octoate as catalyst. It is shown that the composition of the polymers can be chosen in such a manner that the materials’ mechanical and thermal properties can be predetermined. A solvent-casting and particulate leaching scaffold preparation technique has been developed and used to create three-dimensional structures with interconnected pores. The achieved physical properties of these materials’ should facilitate their use in both soft and hard tissue regeneration.</p><p>Well defined star-shaped polyesters have been synthesized using a spirocyclic tin initiator where L-lactide was chosen as a model system for the investigation of the polymerization kinetics. Neither the temperature nor the solvent affects the molecular weight or the molecular weight distribution of the star-shaped polymers, which all show a molecular weight distribution below 1.19 and a molecular weight determined by the initial monomer-to-initiator concentration.</p>

The aim of this thesis is to determine the feasibility of an injectable delivery system based on 5-ethylene ketal ε-caprolactone for localized delivery of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) for treating critical limb ischemia. HGF and VEGF were chosen because of their ability to simultaneously stimulate the proliferation and migration of endothelial cells, to initiate the formation of blood vessels and the recruitment of pericytes to stabilize the blood vessels. Homopolymer of 5-ethylene ketal ε-caprolactone and its copolymer with D,L-Lactide were synthesized by ring opening polymerization using hydrophobic initiator (octan-1-ol) or an hydrophilic initiator (MPEG), and stannous octanoate as a co-initiator/catalyst. The resulting polymers were amorphous and viscous liquids at room temperature. The viscosity, biodegradation rate, and release rate were varied by copolymerizing with D,L-lactide and/or initiating with MPEG or octan-1-ol. In vitro, the polymers degraded with surface erosion characterized by a nearly linear mass loss with time with no significant change in number average molecular weight and glass transition temperature. The ratio of EKC to DLLA in the copolymer remained the same throughout the degradation studies. A similar degradation mechanism was observed in vivo when the copolymer initiated with octan-1-ol was implanted subcutaneously in rats. In vivo, the polymer exhibited a moderate chronic inflammatory response, characterized by the presence of neutrophils, macrophages, fibroblasts and fibrous capsule formation. The inflammatory response decreased with time but was still on going after 18 weeks of subcutaneous implantation. Protein release from the polymer was transported by convection through the hydrated polymer region, at a rate determined by the osmotic pressure generated and the hydraulic conductivity of the polymer. Highly bioactive VEGF and HGF were released in a sustained manner, without burst effect for over 41 days when delivered simultaneously, using the osmotic release mechanism. VEGF was released at the rate of 36 ± 7 ng/day for 41 days, while HGF was released at the rate of 16 ± 2 ng/day for 70 days. Factors that influenced release of proteins were their solubility in the concentrated trehalose solution and hydraulic permeability of the polymer. This delivery system can serve as a potential vehicle for controlled release of VEGF and HGF for treating critical limb ischemia or the controlled release of other proteins for other clinical applications. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2012-05-23 10:18:48.307

[EN] The aim of tissue engineering is to develop functional biological substitutes to replace or restore damaged tissues by preparing three-dimensional scaffolds able to accommodate cells plus signaling factors to promote the regeneration of damaged tissue. There is a special interest in developing scaffolds that while providing a favourable environment for cells also possess a degradation rate that can be adapted to the tissue's rate of regeneration. Scaffolds should be porous and possess a pore morphology adapted to the application for which they are designed. They must also be able to hold large quantities of water (hydrogels) while presenting suitable cell/biomaterial interaction. The aim of this thesis is to create chitosan-based three-dimensional porous structures with tunable degradation rates with particular interest in fast degradation rate. Hydrogels of block-copolymer networks were prepared to crosslink the chitosan (CHT) or carboxymethyl chitosan (CmCHT) with either a hydrophobic polymer of low molecular weight, such as poly(&#949;-caprolactone), (PCL) or a hydrophilic polymer such as poly(ethylene glycol), (PEG). The hypothesis was that the degradation of the cross-linker polymer leaves behind large water-soluble polymer chains (protonated chitosan or carboxymethyl chitosan). However, in spite of chitosan's favourable properties, the polymer has relatively slow biodegradation times in enzymatic media that contain lysozyme and even slower in hydrolytic conditions. Chitosan's physical and chemical properties largely depend on its deacetylation degree (DD). In order to analyze these properties, chitosan was synthesized with various DD ranging from 85% to 45%. Water absorption was seen to rise rapidly as deacetylation was reduced. This would appear to contradict the fact that chitin water absorption (low DD) is much lower than that of chitosan. In order to understand this behaviour, it was analyzed the dependence of the degree of network swelling on the parameters determined by the Flory Rhener theory, the elastic properties of the network and the density of the cross-linking according to the sample's water content. The thermal stability of chitosan according to its DD was analysed by thermogravimetry. Different methods were applied to obtain the activation energy. Electrospinning was chosen as the porous membrane preparation technique as it provides thin membranes that can be handled with fiber sizes in the order of microns. The influence of the electrospinning and cross-linking processes on the thermal stability of chitosan was analyzed. Chitosan and carboxymethyl chitosan hydrogels covalently cross-linked with short chains of poly(&#949;-caprolactone), (PCL) and poly(ethylene glycol) (PEG) were synthesized. The formation of networks was confirmed by solubility tests with appropriate solvents for each polymer. Hydrogels that absorbed large quantities of water were obtained, with values that ranged between 90 and 5000%. The calorimetric tests together with the Studies on the kinetics of hydrolytic and enzymatic biodegradation showed three different systems: CmCHT-PEG system that can be classified as stable hydrogel, CHT-PCL system as semidegradable hydrogel and degradable hydrogels with degradation kinetics in the order of days for the CmCHT-PCL system. Finally, biological studies were carried out on porous CmCHT-PCL hydrogels. Mesenchymal stem cells (MSCs) from pig adipose tissue were then cultivated and the results showed that these networks can be used in the organism in tissue engineering applications with degradation times of around a week. / [ES] La ingeniería tisular tiene como finalidad desarrollar sustitutos biológicos funcionales que reemplacen o restauren los tejidos dañados. Se trata de preparar andamiajes tridimensionales (scaffolds) que sean capaces de albergar células y factores de señalización que favorezcan la regeneración del tejido dañado. Existe un especial interés en el desarrollo de scaffolds que proporcionando un entorno favorable a las células, tengan una tasa de degradación que se adapte a velocidad de regeneración del tejido. Los scaffolds deben ser porosos y poseer una morfología del poro adaptada a la aplicación para la que son diseñados. Deben ser capaces de albergar gran cantidad de agua (hidrogeles) al tiempo que presentan una interacción célula/biomaterial adecuada. El objetivo de esta tesis es el de crear estructuras porosas tridimensionales basadas en quitosano con velocidades de degradación ajustables con particular interés en velocidades de degradación altas. Se han preparado hidrogeles de redes de copolimeros en bloque entrecruzando el quitosano, (CHT) o el carboximetil quitosano, (CmCHT) con un polímero hidrófobo de bajo peso molecular como la poli(&#949;-caprolactona), (PCL) o bien con un polímero hidrófilo como es el poli(etilenglicol), (PEG). La hipótesis de trabajo fue que la degradación del polímero que actúa como entrecruzador debe dejar grandes cadenas del polímero (quitosano protonado o carboximetil quitosano) que son solubles en agua. A pesar de las buenas propiedades del quitosano, el polímero presenta tiempos de biodegradación bastante lentos en medio enzimático conteniendo lisozima y aún más lentos en condiciones hidrolíticas. Las propiedades físico-químicas del quitosano dependen en gran medida del grado de desacetilación, DD. Con el fin de analizar dichas propiedades se ha llevado a cabo la síntesis de quitosano con DD variando entre 85% y el 45%. Se ha comprobado que la absorción de agua aumenta rápidamente a medida que el grado de desacetilación disminuye. Esto parece contradecir el hecho de que la absorción de agua de la quitina (DD bajo) es mucho menor que la de quitosano. Para entender dicho comportamiento se han analizado los parámetros que determinan la teoría de Flory Rhener, las propiedades elásticas de la red y la densidad de entrecruzamiento en función del contenido en agua de la muestra. La estabilidad térmica del quitosano en función de DD ha sido analizada por termogravimetría. Se han aplicado diferentes métodos para obtener la energía de activación. Como técnica de preparación de membranas porosas se ha elegido el electrohilado, ya que permite obtener membranas delgadas y manipulables con tamaños de fibra del orden de micras. Se ha analizado la influencia de los procesos de electrohilado y entrecruzamiento en la estabilidad térmica del quitosano. Se han sintetizado hidrogeles de quitosano, y carboximetil quitosano entrecruzados covalentemente con cadenas cortas de poli(&#949;-caprolactona), y poli(etilenglicol). La formación de las redes se ha confirmado mediante ensayos de solubilidad con buenos solventes para cada polímero. En todos los casos se han obtenido hidrogeles que absorben gran cantidad de agua con valores que oscilan entre 90 y 5000%. Los estudios de las cinéticas de biodegradación tanto hidrolítica como enzimática revelan la obtención de tres sistemas que se pueden clasificar como hidrogeles estables, para los hidrogeles formados por CmCHT-PEG, hidrogeles semidegradables para el sistema CHT-PCL y finalmente hidrogeles degradables con cinéticas de degradación del orden de días, para el sistema CmCHT-PCL. Finalmente se ha llevado a cabo estudios biológicos de los hidrogeles porosos de CmCHT-PCL. Se realizaron cultivos con células mesenquimales del tejido adiposo de cerdo (MSCs). Los resultados han revelado que dichas redes pueden ser utilizadas como sistemas de liberación de células en el organismo con tiempos de degradación / [CA] L'enginyeria tissular té com a finalitat desenvolupar substituts biològics funcionals que reemplacen o restauren els teixits danyats. Es tracta de preparar suports tridimensionals (esquelets o scaffolds) que siguen capaços d'albergar cèl.lules i factors de senyalització que afavorisquen la regeneració del teixit danyat. Hi ha un interès especial en el desenvolupament d'esquelets que, proporcionant un entorn favorable a les cèl.lules, tinguen una taxa de degradació que s'adapte a la velocitat de regeneració del teixit. Els scaffolds han de ser porosos i han de tenir una morfologia del porus adaptada a l'aplicació per a la qual són dissenyats. Han de ser capaços d'albergar una gran quantitat d'aigua (hidrogels) alhora que presenten una interacció cèl.lula/biomaterial adequada. L'objectiu d'aquesta tesi és crear estructures poroses tridimensionals basades en quitosan amb velocitats de degradació sintonizables amb un interés particular de rutes de degradació altes. S'han preparat hidrogels de xarxes de copolímers en bloc entrecreuant el quitosan o el carboximetil quitosan amb un polímer hidròfob de baix pes molecular com la poli (&#949;-caprolactona), o bé amb un polímer hidròfil com és el poli (etilenglicol). Es tracta d'aconseguir que quan el polímer que actua com a entrecreuador es degrade, deixe grans cadenes del polímer (quitosan protronat o carboximetil quitosan) que són solubles en aigua. A pesar de les bones propietats del quitosan, el polímer presenta cinètiques de biodegradació lentes en condicions enzimàtiques quan conté lisozima i encara més lentes en condicions hidrolítiques. Les propietats fisicoquímiques del quitosan depenen en gran mesura del grau de desacetilació, DD. A fi d'analitzar aquestes propietats, s'ha dut a terme la síntesi de quitosan amb un DD que variava entre el 85% i el 45%. S'ha comprovat que l'absorció d'aigua augmenta ràpidament a mesura que el grau de desacetilació disminueix. Això sembla que contradiu el fet que l'absorció d'aigua de la quitina (DD baixos) és molt menor que no la de quitosan. Per a entendre aquest comportament s'ha analitzat la dependència del grau d'unflament de la xarxa amb els paràmetres que determina la teoria de Flory Rhener, les propietats elàstiques de la xarxa i la densitat d'entrecreuament en funció del contingut en aigua de la mostra. L'estabilitat tèrmica del quitosan en funció del DD ha sigut analitzada per termogravimetria. S'han aplicat diversos mètodes per obtenir l'energia d'activació. Com a tècnica de preparació de membranes poroses s'ha utilitzat l'electrofilatura, ja que permet obtenir membranes primes i manipulables amb grandàries de fibra de l'ordre de micres. S'ha analitzat la influència dels processos d'electrofilatura i entrecreuament amb l'estabilitat tèrmica del quitosan. S'han sintetitzat hidrogels de quitosan i carboximetil quitosan entrecreuats covalentment amb cadenes curtes de poli(&#949;-caprolactona) i poli(etilenglicol). La formació de les xarxes s'ha confirmat per mitjà d'assajos de solubilitat amb bons solvents per a cada polímer. En tots els casos s'han obtingut hidrogels que absorbeixen una gran quantitat d'aigua, compresa en valors que oscil.len entre el 90 i el 5.000%. Els estudis de les cinètiques de biodegradació tant hidrolítica com enzimàtica revelen l'obtenció de tres sistemes que es poden classificar com a hidrogels estables (per als hidrogels formats per CmCHT-PEG), hidrogels semidegradables (per al sistema CHT-PCL) i, finalment, hidrogels degradables amb cinètiques de degradació de l'ordre de dies (per al sistema CmCHT-PCL). Finalment s'ha dut a terme estudis biològics dels hidrogels porosos de CmCHT-PCL. Es van realitzar cultius amb cèl.lules mesenquimals del teixit adipós de porc (MSCs). Els resultats han revelat que aquestes xarxes poden ser utilitzades com a sistemes d'alliberament de cèl.lules en l'organisme amb temps de degradació de l'ordre d'una setm / Gámiz González, MA. (2016). Biodegradable hydrogels based on water-soluble chitosan for cell transplant [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/73070 / TESIS

Narrow molecular weight fractions of Poly(ε-caprolactone) were successfully obtained using the successive precipitation fractionation technique with toluene/n-heptane as a solvent/nonsolvent pair. Calorimetric studies of the melting behavior of fractions that were crystallized either isothermally or under constant cooling rate conditions suggested that the isothermal crystallization of the samples should be used for a proper evaluation of the molecular weight dependence of the observed melting temperature and degree of crystallinity in PCL. The molecular weight and temperature dependence of the spherulitic growth rate of fractions was studied in the context of the Lauritzen-Hoffman two-phase model and the Strobl three-phase model of polymer crystallization. The zero-growth rate temperatures, determined from spherulitic growth rates using four different methods, are consistent with each other and increase with chain length. The concomitant increase in the apparent secondary nucleation constant was attributed to two factors. First, for longer chains there is an increase in the probability that crystalline stems belong to loose chain-folds, hence, an increase in fold surface free energy. It is speculated that the increase in loose folding and resulting decrease in crystallinity with increasing chain length are associated with the ester group registration requirement in PCL crystals. The second contribution to the apparent nucleation constant arises from chain friction associated with segmental transport across the melt/crystal interface. These factors were responsible for the much stronger chain length dependence of spherulitic growth rates at fixed undercooling observed here with PCL than previously reported for PE and PEO. In the case of PCL, the scaling exponent associated with the chain length dependence of spherulitic growth rates exceeds the upper theoretical bound of 2 predicted from the Brochard-DeGennes chain pullout model. Observation that zero-growth and equilibrium melting temperature values are identical with each other within the uncertainty of their determinations casts serious doubt on the validity of Strobl three-phase model. A novel method is proposed to determine the Porod constant necessary to extrapolate the small angle X-ray scattering intensity data to large scattering vectors. The one-dimensional correlation function determined using this Porod constant yielded the values of lamellar crystal thickness, which were similar to these estimated using the Hosemann-Bagchi Paracrystalline Lattice model. The temperature dependence of the lamellar crystal thickness was consistent with both LH and the Strobl model of polymer crystallization. However, in contrast to the predictions of Strobl’s model, the value of the mesomorph-to-crystal equilibrium transition temperature was very close to the zero-growth temperature. Moreover, the lateral block sizes (obtained using wide angle X-ray diffraction) and the lamellar thicknesses were not found to be controlled by the mesomorph-to-crystal equilibrium transition temperature. Hence, we concluded that the crystallization of PCL is not mediated by a mesophase. Metallocene-catalyzed linear low-density (m-LLDPE with 3.4 mol% 1-octene) and conventional low-density (LDPE) polyethylene blends of different compositions were investigated for their melt-state miscibility and concurrent crystallization tendency. Differential scanning calorimetric studies and morphological studies using atomic force microscopy confirm that these blends are miscible in the melt-state for all compositions. LDPE chains are found to crystallize concurrently with m-LLDPE chains during cooling in the m-LLDPE crystallization temperature range. While the extent of concurrent crystallization was found to be optimal in blends with highest m-LLDPE content studied, strong evidence was uncovered for the existence of a saturation effect in the concurrent crystallization behavior. This observation leads us to suggest that co-crystallization, rather than mere concurrent crystallization, of LDPE with m-LLDPE can indeed take place. Matching of the respective sequence length distributions in LDPE and m-LLDPE is suggested to control the extent of co-crystallization. / Ph. D.

The use of degradable biomedical materials has during the past decades indeed modernized medical science, finding applications in e.g. tissue engineering and drug delivery. The key question is to adapt the material with respect to mechanical properties, surface characteristics and degradation profile to suit the specific application. Degradation products are generally considered non-toxic and they are excreted from the human body. However, large amounts of hydroxy acids may induce a pH decrease and a subsequent inflammatory response at the implantation site. In this study, macromolecular design and a combination of cross-linking and adjusted hydrophilicity are utilized as tools to control and tailor degradation rate and subsequent release of degradation products from biomedical polyester-ethers. A series of different homo- and copolymers of -caprolactone (CL) and 1,5-dioxepan-2-one (DXO) were synthesized and their hydrolytic degradation was monitored in phosphate buffer solution at pH 7.4 and 37 °C for up to 546 days. The various materials comprised linear DXO/CL triblock and multiblock copolymers, PCL linear homopolymer and porous structure, and random cross-linked homo- and copolymers of CL/DXO using 2,2’-bis-(ε-caprolactone-4-yl) propane (BCP) as a cross-linking agent. The results showed that macromolecular engineering and controlled hydrophilicity of cross-linked networks were useful implements for customizing the release rate of acidic degradation products in order to prevent the formation of local acidic environments and thereby reduce the risk of inflammatory responses in the body. / QC 20101109

The use of synthetic materials for tissue and organ reconstruction, i. e. tissue engineering, has become a promising alternative to current surgical therapies and may overcome the shortcomings of the methods in use today. The challenge is in the design and reproducible fabrication of biocompatible and bioresorbable polymers, with suitable surface chemistry, desirable mechanical properties, and the wanted degradation profile. These material properties can be achieved in various manners, including the synthesis of homo- and copolymers along with linear and star-shaped architectures. In many applications the materials’ three-dimensional structure is almost as important as its composition and porous scaffolds with high porosity and interconnected pores that facilitate the in-growth of cells and transportation of nutrients and metabolic waste is desired. In this work linear and star-shaped polymers have been synthesized by ring-opening polymerization using a stannous-based catalyst and a spirocyclic tin initiator. A series of linear copolymers with various combinations of 1,5-dioxepane-2-one (DXO), Llactide (LLA) and ε-caprolactone (CL) have been polymerized using stannous octoate as catalyst. It is shown that the composition of the polymers can be chosen in such a manner that the materials’ mechanical and thermal properties can be predetermined. A solvent-casting and particulate leaching scaffold preparation technique has been developed and used to create three-dimensional structures with interconnected pores. The achieved physical properties of these materials’ should facilitate their use in both soft and hard tissue regeneration. Well defined star-shaped polyesters have been synthesized using a spirocyclic tin initiator where L-lactide was chosen as a model system for the investigation of the polymerization kinetics. Neither the temperature nor the solvent affects the molecular weight or the molecular weight distribution of the star-shaped polymers, which all show a molecular weight distribution below 1.19 and a molecular weight determined by the initial monomer-to-initiator concentration. / QC 20101217