Le biofilm est défini comme une communauté microbienne adhérant à une surface biotique ou abiotique, et engluée dans une matrice extracellulaire auto-produite. Les biofilms naturels sont composés de plusieurs espèces microbiennes et leurs interactions, qu'elles soient synergiques ou antagonistes, jouent un rôle important dans le développement, la composition et le fonctionnement des consortia impliqués. De plus, ces relations impliquent souvent la production de molécules antagonistes limitant la croissance ou l'adhésion bactérienne. Enfin la composition de la matrice extracellulaire joue un rôle important dans la robustesse du biofilm. Au cours de ce travail, l'étude des interactions au sein de biofilms mixtes constitués par K. pneumoniae et S. epidermidis a permis d'isoler un polysaccharide produit par K. pneumoniae, capable d'inhiber l'adhésion aux surfaces abiotiques de plusieurs autres espèces bactériennes à Gram-négatif et à Gram-positif. La caractérisation physico-chimique de cette molécules de haut poids moléculaire a permis de mettre en évidence qu'elle était composée de galactose, glucose, rhamnose et d'acide glucuronique. Par ailleurs, l'analyse d'extraits de mutants déficients pour la production de capsule a montré que ce polysaccharide correspondait à la capsule de K. pneumoniae. Son mode d'action consisterait à inhiber les interactions initiales entre bactéries et surface. Le suivi dans le temps de la formation de biofilm monospecies par K. pneumoniae avec la technique Biofilm Ring Test® a également permis de mettre en évidence un phénotype original. En effet, la détection initiale d'agrégats bactériens est suivie par une modification apparente de leur structure, qui serait liée à des changements de leur robustesse face aux forces d'aimantation magnétique. La présence d'ADN extracellulaire au sein de la matrice du biofilm pourrait jouer un rôle dans la survenue de ce phénotype comme l'indique les mesures effectuées en présence de l'enzyme DNAse I. En parallèle, l'observation de biofilm formés par K. pneumoniae dans des modèles expérimentaux cinétiques a mis en évidence des décrochements massifs de biomasse au cours de la maturation du biofilm, qui pourraient être corrélées aux modifications internes de robustesse de la matrice. L'ensemble de ces données permet de mieux caractériser les interactions intimes survenant à l'intérieur de biofilms constitués par K. pneumoniae et à terme de mieux caractériser et donc prévenir leur formation et dissémination. / Biofilms are defined as microbial communities adhering to biotic or abiotic surfaces and embedded in a self-produced extracellular matrix. Natural biofilms are composed of several microbial species and their interactions, synergistic or antagonistic, play important roles in development, composition and functioning of the consortia. Furthermore, the relationships often involve the production of antagonist molecules that impair competitors' growth or adhesion. The composition and evolution of the extracellular matrix plays also an important role in the biofilms' robustness. In this work, study of the interactions within biofilms formed by K. pneumoniae and S. epidermidis led to the isolation of a polysaccharide produced by K. pneumoniae able to inhibit the adherence to abiotic surfaces of several Gram-negative and Gram-positive bacterial species. The physico-chemical characterization of this high molecular weight molecule showed it was composed of galactose, glucose, rhamnose and glucuronic acid. This data, together with the analysis of extracts from capsule-deficient mutants, indicated that the capsule of K. pneumoniae was responsible for the biofilm inhibition phenotype, probably by inhibiting the initial interactions between bacteria and surface. By monitoring the formation of monospecies biofilm by K. pneumoniae with the Biofilm Ring Test® technique, we were able to detect an original phenotype. Indeed, detection of bacterial aggregates still occurred after a few hours of incubation but in a different way, probably related to changes of the biofilm robustness towards magnetic forces. The presence of extracellular DNA in the matrix of the biofilm is likely to play a role in the occurrence of this phenotype, as indicated by the assays performed in presence of the enzyme DNase I. At the same time, observations of biofilm formed by K. pneumoniae in kinetic experimental models showed massive detachment events during biofilm maturation, which could be correlated to changes in internal strength of the matrix. All these dtat contribute to a better characterization of the intimate interactions occuring within biofilms formed by K. pneumoniae and will ultimately lead to the development of efficient anti-biofilm strategies.

Marine capture fisheries contribute over 50% of total world fish production and more than 70% of this production is utilized for processing. The Canadian commercial fishing industry is one of the world’s most valued industries but generates large quantities of solid waste and wastewater. The increasing growth of the fish processing industry, the need for reduction of pollutants and the need to increase returns on raw material has led fish processors to adopt new ways of utilizing the wastes. In particular, efforts have focused on converting the biological substance in solid fish processing waste to various valuable compounds including both nutritional and non-nutritional products. Sulfated glycosaminoglycans (sGAGs) are heteropolysaccharide molecules with potential therapeutic applications and anticoagulant properties. Anticoagulants are responsible for curing major death-causing diseases such as strokes and cardiovascular diseases. The aim of this study was to develop an economically feasible technique to extract sulfated glycosaminoglycans (sGAGs) from fish processing waste. Two different fish (mackerel and herring) were used to optimize the extraction of sGAG. The effects of hydrolysis time (3, 6, 12 and 24 hrs) and papain concentration (15 and 20u/ml) on the extraction of sGAGs from different fish parts (whole fish, flesh, head, gut, fins and tails, skin and bones) were evaluated. The highest concentration of sGAGs (206.7 mg/g) was obtained from the mackerel head sample at 6 hrs of hydrolysis time and 20 u/ml of enzyme concentration while the highest concentration of sGAGs (236.3 mg/g) was obtained from herring gut at 12 hrs of hydrolysis time and 20 u/ml of enzyme concentration. The concentration of sGAG obtained from other part of mackerel were flesh (23.96 mg/g), waste (163.23 mg/g), fins and tail (86.63 mg/g), gut (203.52 mg/g), skin (105.45 mg/g) and bones (97.2 mg/g). However, the concentration of sGAG obtained from other parts of herring were flesh (39.34 mg/g), waste (130.15 mg/g), head (162.76 mg/g), fins and tail (148.53 mg/g), skin (65.89 mg/g) and bones (75.57 mg/g). Comparing the overall concentration of sGAG in waste samples of the fish, the mackerel produced higher sGAG than the herring.

Des nanocapsules (NCs) biodégradables contenant une substance active et destinées à des applications environnementales ont été élaborées par un procédé d’émulsion-évaporation de solvant couplé à une réaction de chimie « click » interfaciale. Deux types de réactions « click » ont été testés: (i) cycloaddition azide-alcyne catalysée par le Cu(I) et (ii) thiol-ène. Ces NCs sont constituées d’une écorce en polymère hydrophobe (polylactide) entourant un cœur liquide (Miglyol®810) et recouverte d’une couronne hydrophile polysaccharide (dextrane). Des nanosphères (sans cœur liquide) ont aussi été produites. Ces nano-objets ont été caractérisés en termes de distribution de tailles, morphologie, taux et épaisseur de recouvrement en dextrane ainsi qu’efficacité de couplage « click ». La stabilité colloïdale en milieu salin et la stabilité du recouvrement en présence d’un tensioactif compétitif ont été étudiées. Enfin, une substance active a été encapsulée et libérée à partir des nano-objets / Biodegradable nanocapsules allowing encapsulation of active substances for environmental applications were produced by emulsion-evaporation method combined with a “click” reaction occurring at the liquid/liquid interface of emulsion droplets. Two types of “click” reaction were tested: (i) copper-catalyzed azide-alkyne cycloaddition (CuAAC) and (ii) thiol-ene reaction. The NCs are composed of a hydrophobic polymer shell (polylactide), a liquid core (Miglyol®810) and a hydrophilic polysaccharide coating (dextran). For comparison, nanospheres (without oily core) were also prepared. These nano-objects were characterized in terms of size distribution, dextran coverage density and thickness, “click” coupling efficiency and morphology. Colloidal stability in NaCl solutions as well as dextran coverage stability against an anionic competitive surfactant were also studied. Finally, an active substance was encapsulated and released from these nano-objects

L'acide hyaluronique est un polysaccharide fortement hydraté. Grâce à sa présence naturelle dans le corps humain et aux nombreuses possibilités de modifications chimiques de ce polysaccharide, l'acide hyaluronique est un bon candidat pour la conception de transporteurs de principes actifs. Dans cette thèse, nous avons synthétisé différents types de dérivés du HA en milieu aqueux. Ceux-ci comprennent les dérivés alkylés du HA, HA-cyclodextrine conjugués et des copolymères «hybrides» composés de HA et d'un copolymère thermosensible de l'éthylène glycol.Basé sur la capacité d'accueillir des molécules hydrophobes paclitaxel dans leurs hydrophobes "nanocavités", nous avons ensuite montré la formation de multicouches de polyélectrolytes de capsules à partir de ces dérivés du HA. L'insertion des molécules paclitaxel dans la paroi des capsules a été réalisée par pré-complexation avec les dérivés du HA en solution, et ensuite déposition ces PTX-polyélectrolytes avec le poly(L-lysine) selon la technique de couche par couche.Dans les deux cas, les capsules chargées de PTX ont été trouvés qu'elles permettent de réduire la viabilité et la prolifération des cellules cancéreuses. Ces multicouches ouvrent de nouvelles voies vers des applications en nanomédecine, comme systèmes transporteurs de médicaments hydrophobes. L'acide hyaluronique modifié par maleimide a été réagit avec poly(diethyleneglycolmethacrylate - oligoethyleneglycolmethacrylate (poly(DEGMA-co-OEGMA)) modifié par thiol afin d'obtenir le copolymère «hybrides» thermosensible. La valeur de la LCST de ce copolymère de HA est autour de 35 °C en déterminant par les mesures du point de trouble des solutions. Au-dessus de cette température, le HA-poly(DEGMA-co-OEGMA) conduit à la formation des nanogels avec la capacité d'encapsuler des molécules hydrophobes dans leur domaine hydrophobe.Les nanogels chargés en PTX ont montré une cytotoxicité plus élevée avec des cellules du cancer surexprimant le récepteur CD44. Ces résultats suggèrent que ces nanogels thermosensible pourraient s'avérer être des candidats intéressants pour la libration thérapeutique dans le traitement de cancer. / Hyaluronic acid is a highly hydrated polysaccharide of great biological interest. It can be easily chemically modified, resulting in many kinds of functional polysaccharide derivatives. In this thesis, we have synthesized different types of HA derivatives in aqueous media. These comprise alkylated HA derivatives, HA-cyclodextrin conjugates, and hybrid copolymers made of HA and of a thermosensitive ethylene glycol copolymer. Based on the ability of alkylated HA and cyclodextrin grafted HA to accomodate hydrophobic molecules paclitaxel into their hydrophobic “nanocavities”, we then demonstrated the formation of polyelectrolyte multilayer capsules based on these HA derivatives. The loading of PTX in the nanoshell was achieved by first complexing PTX with HA derivatives in solution and then, depositing these PTX-containing polyelectrolytes alternately with poly(L-lysine) according to the layer-by-layer technique. In the two cases, the PTX loaded capsules were found to decrease the viability and proliferation of MDA MB 231 breast cancer cells, while unloaded capsules did not impact cell viability. Due to these promising results, these hydrophobic polysaccharide nanoshells open new avenues for applications of hydrophobic drug-carrier systems in nanomedicine.Thiol modified poly(diethyleneglycolmethacrylate - oligoethyleneglycolmethacrylate (poly(DEGMA-co-OEGMA)) was reacted with a HA-maleimide conjugate to obtain HA- poly(DEGMA-co-OEGMA). The LCST value of this HA-copolymer was determined to be around 35°C via turbidity measurements. At the body temperature, HA-copolymer was thus shown to self-assemble into nanogels with the ability to encapsulate hydrophobic molecules into their hydrophobic domain. . In vitro cell culture studies showed that with incorporating the hydrophobic anti-cancer drug paclitaxel, the nanogels exhibited high efficiency and selectivity in the eradication of CD44 positive human ovarian cancer cells. These results suggest that these temperature-triggered nanogels hold great potential for the delivery of chemotherapeutics in anti-cancer therapy.

Les alginates forment des gels transparents en solution aqueuse en présence de certains ions divalents. Cette propriété est principalement attribuée à la formation de zones de jonction impliquant les séquences (1->4)-a-L-guluronane de chaînes adjacentes. Des oligomères d'alginates ont été utilisés comme briques élémentaires pour la synthèse de polymères biohybrides contenant des chaines pendantes oligo-(1->4)-a-L-guluronane. La rhéologie et la diffusion de la lumière ont permis d'étudier leur gélification ionotropique. De plus, une image atomistique des associations entre chaines latérales a été donnée grâce à la modélisation moléculaire et la microscopie de force atomique. Les polymères biohybrides portant des résidus pendant (1->4)-a-L-guluronane forment des gels en présence de Ca2+. L'addition de blocs guluronane ou mannuronane au gel préformé fait diminuer sa force avec quasiment la même efficacité. L'étude par dynamique moléculaire de séquences (1->4)-a-L-guluronan totalement chargées en présence d'ions Ca2+ suggère qu'environ 8 unités de répétition sont suffisantes pour former spontanément des zones de jonction. De plus, l'analyse conformationnelle de duplexes de chaines (1->4)-a-L-guluronane ayant 12 unités de répétition révèle une grande variété de conformations accessibles, ce qui est consistant avec la difficulté d'obtention de cristaux de Ca2+-guluronate de dimension suffisante pour les études cristallographiques. Les forces d'adhésion entre des homo-oligomères d'alginates en présence de Ca2+ mesuré par spectroscopie de force atomique montrent que la force d'interaction croit selon l'ordre suivant: M-M < M-G or G-M < G-G. Un résultat important est que les blocs mannuronanes, en complexe avec le calcium, peuvent être impliqués dans des associations homotypiques et hétérotypiques. Ce résultat est consistant avec la détection d'agrégats d'oligomères de mannuronanes observés en diffusion de la lumière pendant l'addition de CaCl2. Les blocs M contribuent donc également à la formation du gel mais la force associée est plus faible que celle des blocs G. / Alginates form transparent hydrogels in aqueous solution upon addition of some divalent cations. This property is mostly due to the formation of junction zones involving (1->4)-a-L-guluronan sequences on adjacent polymer chains. Oligomers of alginates were used as molecular bricks for the synthesis of biohybrid polymers featuring (1->4)-a-L-guluronan sequences as side chains. Rheology and Light Scattering have been applied to investigate their ionotropic gelation. In addition, an atomistic picture of the Ca2+-driven side chain associations was also provided thanks to Molecular Modeling and Atomic Force Spectroscopy. Biohybrid polymers carrying (1->4)-a-L-guluronan residues formed soft and transparent hydrogels in the presence of Ca2+. The addition of either guluronan, or mannuronan blocks to the pre-formed gel reduced its strength almost with the same efficiency. A molecular dynamics investigation of fully charged (1->4)-a-L-guluronan sequences in the presence of a neutralizing amount of Ca2+ ions suggested that about 8 repeating units may be sufficient to the spontaneous formation of junction zones. Furthermore, conformational analysis of (1->4)-a-L-guluronan chain having 12 repeating units in duplexes revealed a wide variety of accessible conformations, a feature consistent with the general difficulty in obtaining crystals of Ca2+-guluronate with suitable lateral dimensions for crystallographic studies. The adhesion forces between homo-alginate oligomers in the presence of Ca2+ measured by Atomic Force Spectroscopy showed that the strength of interactions increased in the following order: M-M < M-G or G-M < G-G. One of the most significant findings to emerge from this study is that mannuronan blocks complexed via calcium ions can be involved in both homotypic and heterotypic associations. This result is consistent with the detection of aggregates observed for mannuronan oligomers by Light Scattering during the addition of CaCl2. Thus, M-blocks also contribute to the gel formation but their strength seemed to be however weaker than G-blocks.

Cereus triangularis est un cactus non endémique de la sous-famille des Cactoïdées très présent dans le nord de Madagascar. Ses cladodes sont utilisées sous la forme de décoctions dans la pharmacopée Malgache. Bien que riche en hydrocolloides comme la plupart des cactus appartenant à cette sous famille il n’est pas exploité pour la production de polysaccharide. Notre travail a donc consisté à définir les conditions d’extraction des polysaccharides hydrosolubles des cladodes de cette plante, à en identifier la structure, à en caractériser les propriétés physico-chimiques et à explorer des voies enzymatiques pour leur dégradation en oligomères et/ou en polymères de faibles masses molaires. Nos travaux ont conduit à l’identification d’un arabinogalactane de type I de haute masse molaire. Ce polysaccharide est constitué d’une chaîne principale de galactane de type β-(1,4)-D-GalP substituée en position 3 par des groupements T-α-L-Araƒ-(1, ou des chaînes latérales d’arabinanes. Le comportement rhéologique de ce galactane est typique des polymères rheofluidifiants ayant des propriétés de gel faible. La mise en œuvre de dégradations enzymatique à l’aide d’une galactanase fongique a conduit à l’obtention de fractions de plus faibles masses molaires que celles des polymères natifs qui ont pu être testées avec succès pour leurs propriétés prébiotiques. / Cereus triangularis is a non endemic cactus belonging to the sub-family of Cactoideae, well represented in the north of Madagascar. Its cladodes are used in food decoction as a traditional medicine in Madagascar. Even if the hydrocolloid content of this cactus is high as observed with other ones from the same sub-family, it is not exploited for the production of polysaccharides. In this study we have defined an extraction procedure to collect the soluble polysaccharide from the cladodes of this cactus and characterized the structure of it before to investigate its physico-chemical properties and to degrade it into oligosaccharides using enzymes. Structural analyses have revealed that this polysaccharide is a type I arabinogalactan with a high molecular weight. It is mainly composed of a galactan backbone of β-(1,4)-D-GalP substituted at position 3 by T-α-L-Araƒ-(1, or arabinan chains. The rheological properties of this galactan are characteristic of a pseudoplastic fluid with a weak gel behavior. Its enzymatic degradation using a fungal galactanase led to the production of oligomers and low molecular weight polysaccharides which have been successfully tested as prebiotics.

La chimie se doit de développer de nouveaux axes de recherche à la fois respectueux de la nature et s’inscrivant dans une démarche globale éco-compatible. Dans ce contexte, l’utilisation des polymères naturels, notamment les polysaccharides, permet de synthétiser des matériaux innovants des applications dans de nombreux secteurs industriels. L’objectif de ce travail est de valoriser les polysaccharides marins tels que le chitosane et le κ-carraghénane à travers l’exploration de deux axes de recherches. Le premier axe est consacré à l’amélioration des propriétés mécaniques, électriques et de sorption de biopolymères par l’incorporation de graphène. Un protocole original a permis de disperser très efficacement du graphène au sein du chitosane pour la conception de films et d’aérogels nanocomposites. L’analyse des films a mis en évidence une amélioration simultanée de la rigidité, de la résistance, et de l’élongation à rupture, pour de faibles teneurs en graphène. Le seuil de percolation permettant l’obtention d’une conductivité électrique n’a pas été atteint aux faibles taux de charges utilisés. L’étude des aérogels chitosane/graphène a, quant à elle, révélé que l’incorporation de graphène aux aérogels de chitosane permettait d’augmenter leur capacité d’adsorption de colorants.Le deuxième axe concerne l’introduction d’hétéroatomes dans la structure carbonée du graphène. Pour obtenir du graphène dopé en azote et en soufre, des aérogels de polysaccharides marins ont été synthétisés, puis pyrolysés dans des conditions contrôlées. Les aérogels carbonés obtenus sont ensuite exfoliés dans l’eau par l’utilisation d’ultrasons. Les groupements amine du chitosane ont permis d’obtenir avec un haut rendement un graphène dopé avec un taux de 5 % d’azote. De plus, il a été possible de moduler de 5 % à 11 %ce taux d’azote par l’emploi de liquide ionique tel que le [EMIm][dca]. De façon similaire, les groupements sulfate du κ-carraghénane ont permis de doper du graphène en soufre avec un taux d’atomes de soufre de 1,5 %. / The chemistry have to develop new research axis both respectful of the nature and joining an eco-compatible global approach. In this context, use natural polysaccharides allow to synthesize innovative materials for applications in many industries fields. The aim of this work is add value to the marine polysaccharide such as chitosan and κ-carrageenan through two research axis.The first axis is consecrated to increase the mechanical, electrical and color sorption properties by introduce graphene filler in biopolymer matrice. An easy and original protocol allowed scattering very effectively graphene in chitosan to design films and aerogels nanocomposites. The analyse of nanocomposite films show an improvement of stiffness, tensile strength and elongation break at the same time with low content of graphene. However, the percolation threshold was not reach to bring electrics properties in films. The study of chitosan/graphene aerogel reveals that graphene allows an increase of color agent adsorbing power such as eosin Y compared with aerogels chitosan.The second axis concerns the introduction of heteroatom in graphene carbon structure. To obtain nitrogen-doped graphene and sulphur-doped graphene, it requires the synthesis of marine polysaccharide aerogel, and their pyrolysis under controlled conditions. The carbon aerogels are exfoliated in water with sonification. Amine groups in chitosan allowed through this process a nitrogen-doped graphene with high yield and nitrogen rate of 5 %. Moreover, it was possible to modulate nitrogen rate with ionic liquid such as [EMIm][dca]. So the nitrogen atom rate increases from 5% to 11%. In similar way, sulfate group in κ-carrageenan gives sulphur-doped graphene with sulphur rate of 1,5%.

Les polysaccharides amphiphiles sont constitués d’un squelette hydrophile sur lequel sont greffés des groupements hydrophobes. Ils possèdent des propriétés rhéologiques accrues dues à leur capacité d’auto-organisation en solution aqueuse mais également interfaciales dues à leurs propriétés d’adsorption aux interfaces eau/huile. Néanmoins, peu d’études s’intéressent à conférer ce type de propriétés à des polysaccharides complexes en termes de structure ou de conformation, comme le xanthane. En effet, ce polymère adopte en solution deux conformations distinctes selon les conditions expérimentales : une forme ordonnée hélicoïdale rigide et une forme désordonnée de type pelote flexible.Partant de ce constat, l’objectif de ce travail de thèse est de déterminer l’impact de la rigidité du squelette du xanthane modifié hydrophobiquement sur les propriétés amphiphiles en solution mais également sur les propriétés stabilisantes en émulsion.Il s’avère que la conformation adoptée par le polymère pendant le processus de greffage a un impact majeur sur ses propriétés rhéologiques : le xanthane modifié sous forme désordonnée possède un caractère associatif, contrairement au xanthane modifié sous forme ordonnée.De plus, le xanthane modifié hydrophobiquement est capable, sous certaines conditions, de former et de stabiliser des émulsions H/E, sans ajout de tensioactif moléculaire, en se partitionnant entre stabilisation de l’interface eau/huile et maintien de la viscosité de la phase aqueuse continue. / Amphiphilic polysaccharides are composed of a hydrophilic backbone grafted with hydrophobic moieties. They show specific rheological properties due to their capacity to self-associate in solution, but also interfacial properties due to their ability to adsorb at the water/oil interface. However, only few studies describe the chemical modification of complex heteropolysaccharides regarding their structure or their conformation, such as xanthan. Indeed, this polysaccharide can adopt in solution two distinct conformations depending on experimental conditions: an ordered rigid helix or a disordered flexible coil.The objective of this work is to determine the impact of the chain stiffness of hydrophobically modified xanthan on associative properties in solution, but also on stabilizing properties in emulsion.The conformation adopted by the polymer during the grafting procedure has a major impact on the rheological properties: xanthan modified under disordered conformation is an associative polysaccharide, contrary to xanthan modified under its ordered conformation.In addition, hydrophobically modified xanthan is able, under certain conditions, to form and stabilize O/W emulsion, without further addition of molecular surfactant, by partitioning between stabilization of the water/oil interface and viscosifying the continuous aqueous phase.

Pneumothorax, or a collapsed lung, is a serious medical condition resulting when air or fluid escapes the lung into the chest cavity and prevents the lung from inflating. Few viable means of sealing the damaged and leaking tissues are currently available, leading to longer hospital stays, multiple interventions, and increasing costs of care. The motivation of this dissertation is to engineer a novel polysaccharide-based therapeutic surgical sealant, which can be utilized to seal trauma-induced damage to the outer lining of the lung, i.e. pleura, preventing or reversing lung collapse to restore normal breathing function. The use of polysaccharides, such as alginate and hyaluronan, has become increasingly prevalent in biomedical and tissue engineering applications due to the ability to add functionality through chemical modification, allowing for tunable mechanical and physical properties. These hydrophilic polymer chains can be crosslinked to form hydrogels, which can retain large volumes of water and can mimic the properties of tissues found within the body. In this work, polysaccharide hydrogel sealants were engineered with well-regulated gelation and mechanical properties, and further modified to achieve adhesion to biological tissues. This was accomplished by mimicking the mechanical and physical properties of the complex tissues, and crosslinking the hydrogels in situ using a visible light-initiated system. Methacrylated alginate and oxidized alginate were successfully synthesized and utilized to fabricate adhesive sealant patches, which can adhere and seal damaged tissues in vivo. Methacrylation was implemented to allow covalent photo-crosslinking between adjacent polymer chains in solution. Here, a novel anhydrous chemistry was developed to allow for precise control over the degree of methacrylation and thus tune the mechanical properties of the resulting hydrogels by modulating the number of crosslinkable side-groups attached to the polysaccharide chain. To increase the adhesive properties of the resulting hydrogels, oxidation of the polysaccharide chain was subsequently implemented to form functional aldehyde groups capable of protein interactions through the formation of imine bonds on biological tissue surfaces. To test the performance of this multifunctional material, burst pressure testing was executed, revealing the relationship between the two distinct chemical modifications performed and the mechanical and adhesive properties of the resulting sealant. In addition, methacrylated alginate was utilized to synthesize therapeutic, drug-encapsulating hydrogel nanoparticles, which when incorporated within the polysaccharide-based surgical sealant allow for local drug release. The ability to control drug release at the site of application further broadens the potential uses of this surgical sealant patch and will be discussed further within this dissertation.

Marshmallow é um dos vários tipos de recheio que podem ser produzidos utilizando-se açúcar, açúcar invertido e xarope de glicose adicionado de gomas ou proteínas, como gelatina e albumina, emulsionados em ar. Foram avaliados quatro produtos de mercado quanto à atividade de água, teor de proteína e sua reologia através de ensaios rotacionais, oscilatórios e tixotropia. Os ensaios reológicos foram realizados em conjunto com imagens de microscopia, podendo assim avaliar além do comportamento da espuma também sua estrutura. Produtos com maior teor de proteína e contendo gomas em sua formulação apresentaram valores de atividade de água menores. O uso de proteínas e gomas confere aos produtos estudados características de géis como observado através da reologia. O valor de yield stress determinado pelos ensaios de amplitude mostrou-se coerente com a vida de prateleira dos produtos, sendo que para valores maiores, maior a vida de prateleira, em relação à estabilidade do produto. Os ensaios oscilatórios sob alta frequência foram comparados com os ensaios rotacionais e demonstraram ser de interesse não só para avaliar o comportamento do produto, como também avaliar a recuperação da estrutura da espuma em função do tempo e tensão aplicados. Através da análise reológica da formulação e da interface, bem como análises da tensão interfacial e microscopia, foram avaliadas as diferentes gomas, em pH 4 e 7,5, determinando assim que a goma &#954;-carragena em pH 4 foi a que apresentou melhores resultados para a estabilidade da espuma. A formulação escolhida com base nos ensaios reológicos de interface e tensão interfacial foi avaliada quanto a sua estabilidade por 60 dias através de ensaios reológicos oscilatórios e microscopia, apresentando estabilidade pelo período estudado. Foi avaliado ainda o tempo de processo necessário para obtenção de um produto estável com melhor capacidade de aeração, levando a um tempo de processo de 15 minutos. / Marshmallow is a kind of aerated filling made from sugar, inverted sugar, glucose syrup, added by polysaccharide and proteins, like gelatin and albumin. Four market products were evaluated regarding water activity, protein content and through dynamic and rotational, besides thixotropy evaluation. Rheological tests were done together with image rheology, evaluating not only product behavior but also the product structure. High protein content product formulated with polysaccharides presented lower water activity values, the use of protein and polysaccharides in the formulations produce gel like products, as can be seeing through rheology. Amplitude sweep determine the yield stress, and it was coherent with the shelf life indicated by each product, higher yield stress raises the product shelf life. Dynamic oscillatory tests under high frequency were compared to rotational tests, and showed to be of interest to evaluate foam behavior and structure recovery as a function of time and stress applied. Interfacial rheology were performed to evaluate different polysaccharides under pH 4 and 7,5, determining that &#954;- carragena at pH presented better results for foam stability. The chosen formulation after rheological tests of interface and surface tension was evaluated for 60 days through dynamic oscillatory tests and microscopy, showing stability for all studied period. Processing time of aeration was also evaluated, and a time of 15 minutes was the processing time with better stability.