La mise au point de nouveaux matériaux possédant des propriétés antibactériennes est un sujet intéressant le monde médical et environnemental. Pour cela, les polymères commerciaux de Merrifield et de Wang-benzaldéhyde ont été modifiés par greffage de motifs calixarèniques polycationiques antibactériens inspirés des travaux du laboratoire et désignés pour interagir avec la surface bactérienne chargée négativement. Ces calixarènes ont été modifiés sur la partie basse, de façon contrôlée, par incorporation d'un groupe espaceur fonctionnel permettant d'accéder à un greffage ciblé du polymère. Nous avons en premier lieu évalué plusieurs types de fonctionnalités introduites sur le calixarène, permettant la fixation de ces motifs sur le support polymérique. Ainsi une amination réductrice a été choisie pour l’ancrage sur la résine de Wang-benzaldéhyde, tandis qu’un point d’ancrage de type pyridinium, pour la résine de Merrifield, a retenu notre attention et s'est avéré être un excellent candidat pour le greffage des calixarènes. La validité de ce point d’ancrage pyridinium a pu être vérifiée par l’incorporation d’une sonde fluorescente (pyrène) et caractérisée par fluorescence à l’état solide, par spectroscopie infrarouge et analyse élémentaire, ces deux dernières étant appliquées à l'ensemble des polymères préparés par la suite. Au travers d'une étude de capture–relargage en milieu aqueux de deux antibiotiques carboxyliques (type quinolone et ß-lactame) le polymère pyridinium modèle, sans calixarène, a montré tout son intérêt, face à la cholestyramine (Questran®) ou à l'Amberlite IRA-400, en tant que résine échangeuse d'anions et pouvant mener à une utilisation en tant que dépolluant/décontaminant. En amont des études antibactériennes de ces nouveaux matériaux nous avons cherché à quantifier la capacité du matériau à retenir/séquestrer des bactéries. L’électrophorèse capillaire, méthode analytique rapide et sensible, s’est présentée comme une solution adéquate. Sur le modèle E. coli., les résines polycationiques synthétisées ont été évaluées en tant que séquestrants en milieu aqueux. Les résultats obtenus prouvent l’efficacité de certaines d’entre elles; la capture a finalement été confirmée par microscopie de fluorescence confocale. Le nombre de bactéries fixées à la surface du matériau a pu être visuellement évalué / Development of new materials with antibacterial properties is a major concern in medical and environmental world. It’s for that reason that, Merrifield and Wang commercial polymers were modified by grafting polycationic calixarenic sub-units inspired by laboratory work and designed to interact with negatively charged bacterial surface. Those calixarenes were modified on the lower part, in a controlled manner, by the incorporation of a functional spacer group leading to a targeted grafting of the polymer. We have, at first, evaluated several kinds of functionalities introduced on the calixarene, giving us the opportunity to graft them on the polymeric support. Like this, a reductive amination was chosen to anchor the Wang-benzaldehyde resin, whereas a pyridinium anchoring point was pointed out as a very good candidate for the grafting of calixarenes. The validation of this pyridinium anchoring point was checked by incorporation of a fluorescent probe (pyrene) and characterized by solid state fluorescence, by infrared spectroscopy, those two lasts analysis were applied for all the other grafted polymers grafted after that. Through a capture-release study in aqueous media of two carboxylic antibiotics (quinolone and ß–lactame kind), the pyridinium polymer model, without calixarène, showed his interest faced to Cholestyramine (Questran®) or Amberlite IRA-400, as an anion exchange resin and leading to depoluting/decontamination applications. Before antibacterial studies of thoses new materials, we wanted to find a way to quantify the material capacity to catch/hold bacteria. Capillary electrophoresis, rapid and sensitive analytical method, appeared as a perfect solution. Using E. coli model, synthesized polycationic resins were evaluated as sequestering agent in aqueous media. Results obtained prove the efficiency of some of them; capture was finally confirmed by confocal fluorescent microscopy. The number of bacteria fixed by material surface could be visually evaluated

La présence d’argile dans les granulats (sables et graviers), influencent considérablement les propriétés rhéologiques des bétons. Considérant les évolutions techniques apportées au béton ces dernières années, la compréhension des mécanismes de nocivité des argiles est donc d’un intérêt majeur sur le plan industriel. Au cours de cette étude, nous avons scindé la problématique en deux parties, la première s’attardant plus spécifiquement sur les mécanismes d’adsorption aux surfaces des argiles. Une analyse fines des interactions polymere-argile par IR, SAXS-WAXS et mesure d’adsorption a alors permis de valider l’adsorption des superplastifiants par les argiles et le rôle bénéfique de l’utilisation de molécule cationique (F25) pour empêcher leur fixation. La détermination d’un processus d’adsorption par échange cationique de ces molécules explique d’une part leur effet inertant et d’autre part la restructuration des particules d’argile à l’échélle du micron comme du nanométre. Dans un deuxième temps, une étude rhéologique des systèmes granulaires a permis de caractériser l’effet intrinséque de argiles sur les propriétés d’écoulement de ces systèmes. L’étude des suspensions d’argile a démontré le rôle de la rétention d’eau par les argiles. L’anisotropie des particules, caractérisée au moyen de différentes techniques (MET, SAXS-WAXS), permet d’expliquer cette rétention d’eau / Clay minerals which can be found in granular materials strongly influence the rheological properties of fresh concrete. Due to the recent technical evolution of concrete, the understanding of the effect of clays in such systems takes on a significant industrial interest. This study was divided into two part, the first one dealing with the adsorption mechanisms of two polymers onto clay surfaces: a superplasticizer (PCP) and a polycation (F25). IR and SAXS-WAXS analysis together with adsorption measurment revealed that superplasticizer are adsorbed by clays and that the used of polycation inhibites clays-PCP interactions. The adsorption process of F25 onto clays by cationic exchange explains the preferential adsorption of cationic compounds rather than PCP and the restructuration of clay particles at the nano and micronic scale during the adsorption. In a second part, the rheological study of granular suspensions revealed a strong effect of clay particles on the flow behaviors of such systems. The rheological study of pure clay suspensions allowed the modelisation of the effect of clays on granular suspensions using excluded volume. In this case, the anistropic features of clays particles characterized by various technics (TEM, SAXS-WAXS) explains water retention properties of such nanometric minerals

This thesis focuses on solution antimicrobial effectiveness for copolyoxetanes with quaternary ammonium and PEG-like side chains. Ring opening copolymerization of 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy) ethoxy) methyl)-3-methyloxetane (ME2Ox) yielded random copolymers with 14-100 (m) mole% BBOx designated P[(BBOx-m)(ME2Ox)]. Reaction of P[(BBOx-m)(ME2Ox)] with dodecyl dimethylamine gave the corresponding quaternary P[(C12-m)(ME2Ox)] polycation salts, designated C12-m. Mole ratios and molecular weights were obtained from 1H-NMR and end group analysis. Differential scanning calorimetry (DSC) studies showed Tg’s between 69 and -34 °C. Minimum inhibitory concentrations (MIC) against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa showed MIC decreasing with increasing C12 mole% reaching a minimum between C12-43 and C12-60. C12-43 had the lowest MIC for all strains. At 5× MIC (challenge:108 cfu/ml), C12 43 kills ≥ 99% of the tested strains within 1 hr. C12-m copolyoxetane cytotoxicity toward human red blood cells, HFF (Human Foreskin Fibroblast) and HDF (Human Dermal Fibroblast) was low, indicating good prospects for biocompatibility. Cx-m copolyoxetane antimicrobial efficacy, hemolytic activity and cytotoxicity were further explored by changing quaternary alkyl chain length. Copolyoxetanes are represented as Cx-50, where 50 is the mole percent quaternary repeat units and ‘x’ is quaternary alkyl chain length (2 to 16 carbons). Reaction of P[(BBOx-m)(ME2Ox)] with a series of tertiary amines yielded the desired quaternary ammonium segment. DSC studies showed Tg’s between -40 °C and -60 °C and melting endotherms for C14-50 and C16-50. A systematic dependence of alkyl chain length on MIC was found with C8-50 being the most effective antimicrobial. Kill kinetics for C8-50 (5× MIC, challenge: 108 cfu/ml) effected >99% kill in 1 hour for S. aureus (7 log reduction). C8-50 efficacy on biomass and cell viability of P. aeruginosa biofilms was investigated. Crystal violet (CV) staining assays demonstrate that C8-50 had no effect on adhesion of already established P. aeruginosa biofilms, but reduced biofilm formation by killing cells prior to attachment. For anti-adhesion assays, noticeable reduction in biofilm mass occurred at concentrations greater than 2× MIC. Viability studies show a substantial log reduction of 2.1 at MIC. The low cytotoxicity of Cx-m copolyoxetanes coupled with low MICs and favorable biofilm results indicate good prospects for therapeutic applications.

The delivery of growth factors has been attempted for a number of different therapies. The approach of delivering therapeutic growth factors in a safe and efficient manner is difficult and certain criteria should be met. These criteria include: binding the appropriate growth factors, maintaining their bioactivity, and delivering these proteins with controllable release kinetics for an extended period of time. These criteria encompass a set of guidelines that hope to mimic in vivo biological events such as neovascularization. The central goal of this thesis is to meet these criteria by introducing a novel delivery strategy for growth factors using a biocompatible polycation and heparin. It was hypothesized that a polycation could interact with heparin to form a complex with the potential to deliver bioactive growth factors with an adaptable release. This hypothesis was tested by examining the release kinetics of bFGF from the complex and investigating whether the released bFGF maintained its bioactivity. The [polycation:heparin:bFGF] complex was formed by mixing the components in water, resulting in a precipitate. This precipitate was able to deliver bFGF with controllable release kinetics and the bioactivity of the released bFGF was higher than bolus bFGF and comparable to heparin stabilized bFGF. This system is expected to have the ability to bind and deliver numerous heparin-binding growth factors. In conclusion, the delivery system developed in this research provides a novel mechanism for controlled release of growth factors. This delivery strategy has met the criteria listed earlier and this research has laid the foundation for a successful delivery vehicle. Further, a biocompatible polycation was synthesized, which is a critical component of the delivery system. This polycation exhibited in vitro and in vivo biocompatibility that was orders of magnitude higher than existing polycations and has the potential to be very useful in a variety of biomedical applications. This design principle is also expected to serve as a platform for the synthesis of other biocompatible polycations.

No description available.

No description available.