To develop a hydrogel sensor system using the Hall effect to detect the degree of swelling, gels containing high concentrations of magnetic particles are necessary to induce a strong magnetic field. For this purpose, hydrogels based on poly(N-isopropylacrylamide) cross-linked with Laponite XLS are modified with various magnetic nanoparticles. The focus of this work is to introduce high particle densities with a homogeneous distribution into the gel. Particles are coated with 3-(trimethoxysilyl)propyl methacrylate to bind them into the network structure. The swelling behavior and temperature response of gels containing pure and modified particles are compared to the unmodified clay gel. Ferrogels are further synthesized in a magnetic field to permanently align magnetic nanoparticles in the network. This results in permanently embedded rod-like structures spanning the entire length of the gel. The influence of this anisotropic distribution on the mechanical properties of the hydrogel is investigated through compression measurements.

Microsystems are a broad category of engineered technologies in the micro and nano scale that have a diverse range of applications. They are emerging as a powerful tool in the field of biomedical research, drug discovery, as well as clinical diagnostics and prognostics, especially with regards to cancer. One of the major challenges in precision and personalized medicine in cancer lies in the technical difficulties of ex-vivo cell culture and propagation of the limited number of primary cells derived from patients. Therefore, our aims are to 1. Develop a biologically relevant platform for culturing cancer cells and characterize how it influences the cell growth and phenotype compared to conventional 2-dimensional(2D) cell culturing techniques, 2. Isolate secondary metabolites from endophytic fungi and screen them on the platform for potential anticancer properties in a preliminary drug discovery pipeline, 3. Design and develop biosensors for quantifying cell responses in real-time within these systems. Several biomaterial scaffolds with microscale architectures have been utilized for engineering the tumor extracellular matrix, but very few studies have thoroughly characterized the phenotypic changes in their cell models, which is critical for translational applications of biomaterial systems. The overall objective of these studies is to engineer a biomimetic platform for the culture of breast cancer cells in vitro and to quantify and profile their phenotypic changes. In order to do this, we first evaluated a blank-slate matrix consisting of thiolated collagen, hyaluronic acid and heparin, cross-linked chemically via Michael addition reaction using diacrylate functionalized poly (ethylene glycol). The hydrogel network was used with triple-negative breast cancer cells and showed significant changes in characteristics, with cells self-assembling to form a 3D spheroid morphology, with higher viability, and exhibiting significantly lower cell death upon chemotherapy treatment, as well as had a decrease in proliferation. Furthemore, the transcriptomic changes quantified using RNA-Seq and Next-Gen Sequencing showed the dramatic changes in some of the commonly targeted pathways in cancer therapy. Furthermore, we were able to show the importance of our biomimetic platform in the process of drug discovery using fungal endophytes and their secondary metabolites as the source for potential anticancer molecules. Additionally, we developed gold nanoparticle and antibody-based (ICAM1 and CD11b) sensors to quantify cell responses spatiotemporally on our platform. We were able to show quenching of the green fluorescent fluorophores due to the Förster Resonance Energy Transfer mechanism between the fluorophore and the gold nanometal surface. We also observed antigen-dependent recovery of fluorescence and inhibition of energy transfer upon the antibody binding to the cell-surface receptors. Future efforts are directed towards incorporating the hydrogel system with antigen-dependent sensors in a conceptually-designed microfluidic platform to spatiotemporally quantify the expression of surface proteins in various cells of the tumor stroma. This includes the migration,infiltration, and polarization of specific immune cells. This approach will provide further insight into the heterogeneity of cells at the single-cell resolution in defined spaces within the 3D microfluidic platform. / Doctor of Philosophy / Microsystems are a broad category of engineered technologies in the micro and nano scale that have a diverse range of applications. They are emerging as a powerful tool in the field of biomedical research, drug discovery, as well as clinical diagnostics and prognostics, especially with regards to cancer. However, a major challenge in being able to offer personalized medicine to cancer patients comes from the difficulty of growing cells from the patient's tumor biopsy in a laboratory for further screening and analysis. There are also limited resources available for real-time expression of proteins on cell-surfaces, that could be potential biomarkers and targets for treatment. Various natural and synthetic polymers are biocompatible and have been used widely in engineering the tumor extracellular matrix. However, the effect of hydrogels derived from these polymers on the specific tumor cells are not always well characterized. Our studies explore the influence of a biohybrid hydrogel on breast cancer cells and our results show that the microscale architecture of the hydrogel platform works as a suitable scaffold for recapitulating the 3-dimensional(3D) breast tumor microenvironment, and can also be employed in the drug discovery process. Additionally, we developed a nano-scale biosensor to enable the quantification of specific cell-surface proteins in real-time. Ongoing and future efforts are focused on designing and fabricating a microfluidic device with precise control over the design of space and special chambers for cell culture. These will be used for studying interactions of various cells in the tumor microenvironment that influence cancer progression. Integrating these micro-scale systems, including sensors will allow researchers to quantify cell behavior in response to the variable factors they are exposed to, as well as provide insight to answer fundamental questions about cancer biology that are limited by the conventional 2D cell culture systems.

As hydrogel products are manufactured and used for applications ranging from biomedical to agricultural, it is useful to characterize their behavior and interaction with other materials. This thesis investigates the adhesion between two different solvated semi-interpenetrating polymer network (S-IPN) silicone hydrogels and a cyclo-olefin (COP) polymer through experimental, analytical, and numerical methods. Interfacial fracture data was collected through the application of the wedge test, a relatively simple test allowing for the measurement of fracture properties over time in environments of interest. In this case, the test was performed at discrete temperatures within range of 4Ë C to 80Ë C. Two COP adherends were bonded together by a layer of one of the S-IPN silicone hydrogels. Upon the insertion of a wedge between the two adherends, debonding at one of the two interfaces would initiate and propagate at a decreasing rate. Measurements were taken of the debond length over time and applied to develop crack propagation rate versus strain energy release rate (SERR) curves. The SERR values were determined through the application of an analytical model derived for the wedge test geometry and to take into account the effects of the hydrogel interlayer. The time-temperature superposition principle (TTSP) was applied to the crack propagation rate versus SERR curves by shifting the crack propagation rates with the Williams-Landel-Ferry (WLF) equation-based shift factors developed for the bulk behavior of each hydrogel. The application of TTSP broadened the SERR and crack propagation rate ranges and presented a large dependency of the adhesion of the system on the viscoelastic nature of the hydrogels. Power-law fits were applied to the master curves in order to determine parameters that could describe the adhesion of the system and be applied in the development of a finite element model representing the interfacial fracture that occurs for each system. The finite element models were used to validate the analytical model and represent the adhesion of the system such that it could be applied to future geometries of interest in which the S-IPN silicone hydrogels are adhered to the COP substrate. <i>[Files modified per J. Austin, July 9, 2013 Gmc]</i> / Master of Science

Yes / This paper outlined our method for developing polymer-linked contact lens type materials for rapid detection and differentiation of Gram-positive, Gram-negative bacteria and fungi in infected corneas. It can be applied to both model synthetic or ex-vivo corneal models and has been successfully trialed in an initial efficacy tested animal study. First a hydrogel substrate for the swab material is selected, we have demonstrated selective swabs using a glycerol monomethacrylate hydrogel. Alternatively any commercial material with carboxylic acid functional groups is suitable but risks nonspecific adhesion. This is then functionalised via use of N-hydroxysuccinimide reaction with amine groups on the specified highly branched polymer ligand (either individually gram negative, gram positive or fungal binding polymers or a combination of all three can be employed for desired sensing application). The hydrogel is then cut into swabs suitable for sampling, used, and then the presence of gram positive, game negative and fungi are disclosed by the sequential addition of dyes (fluorescent vancomycin, fluorescein isothiocyanate and calcofluor white). In summary this method presents: Method to produce glycerol monomethacrylate hydrogels to minimize nonspecific binding Methods of attaching pathogen binding highly branched polymers to produce selective hydrogel swabs Method for disclosing bound pathogens to this swab using sequential dye addition

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal. / Le présent travail s'inscrit dans le domaine de la libération contrôlée des médicaments. Un polymère naturel, la chitosane modifiée par acylation, fait l'objet de l'étude en tant que nouvel excipient pour la fabrication des comprimés à libération prolongée de principe actif. La chitosane est un polysaccharide préparé chimiquement à partir de la chitine par un traitement alcalin à haute température (Muzzareli, 1977). Elle ne possède pas la propriété de former un gel dans un milieu aqueux, cependant, lorsque les molécules de ce polymère sont substituées par des chaînes carbonées, cela génère des dérivés de chitosane capables de gonfler dans l'eau ou dans un tampon phosphate. Le mécanisme de gonflement du polymère substitué est dû à l'éloignement des macromolécules les unes des autres entraînant ainsi un espace diffusionnel. Une telle structure est appelée hydrogel. Les propriétés gélifiantes de ces dérivés de chitosane ont été mises à profit pour l'étude de la cinétique de libération des médicaments. La première section de ce mémoire est une revue des différentes formes à libération contrôlée. La deuxième section est divisée en deux parties : la première décrit la synthèse de trois dérivés de chitosane. Ces derniers sont caractérisés par leur capacité à former un gel en milieu aqueux. Dans la deuxième partie, les systèmes réservoir et matriciel ont été choisis comme modèle pour analyser l'influence du poids moléculaire du médicament ainsi que de la géométrie du comprimé sur la cinétique de libération. Pour déterminer le mécanisme de libération, on a utilisé l'équation de PEPPAS (Peppas, 1987) comme modèle mathématique afin d'interpréter les résultats expérimentaux.

Chapter 1. General Introduction This chapter gives an introduction to supramolecular organo/hydrogels and the related bile acid chemistry touching upon the gelation properties of the bile acid derivatives. Diverse applications of the supramolecular gels are illustrated with several examples. In the concluding section of this chapter, a brief introduction on the semiconductor nanocrystals is provided. Finally, the content of the thesis is outlined. Chapter 2. Bile Acid Derived Novel Organo/hydrogelators Part 1. Bile Acid Derived Organo/hydrogelators With a Basic Side Chain Cationic analogues of bile acids which showed remarkable gelation properties in water were reported from our laboratory. This led us to investigate the aggregation behaviour of some of the lithocholic and deoxycholic acid derivatives having a basic side-chain. Figure 1. Bile acid based organo/hydrogelators containing a basic side-chain. In this part, an organogelator 1 and a hydrogelator 2 derived from parent bile acids have been described with respect to their gelation properties, morphology, thermal and mechanical stability of the gels. The organo/hydrogels were shown to be responsive to acid-base stimuli as the organogel formed only in the protonated state and the hydrogel formed in the neutral form of the tertiary amines. The xerogel fibres obtained from the organogel were found to be solid-like and stable up to 200 oC as confirmed by variable temperature polarizing optical microscopy. The non-fluorescent organogel was doped with a fluorescent dye (coumarin 153) to design a novel dye-organogel composite material which was investigated with laser scanning confocal fluorescence microscopy showing the dye molecules were uniformly deposited on the organogel fibres. Part 2. Serendipitous Organogelation by Dimeric Bile Acid Esters This section highlights our work on the organogelators based on a number of dimeric esters consisting of different bile acid units. Figure 2. The three different dimeric bile acid esters as organogelators. In this part, three bile acid derived dimeric esters (1, 2 and 3) were shown to possess organogelation properties in aromatic and halogenated aromatic solvents. We studied the morphological features and rheological properties of these organogels. Next, the organogel matrix was exploited to generate and stabilize gold nanoparticles and prepare AuNP/gel hybrid material. Chapter 3. Cholate Hydrogels and Soft Gel-nanoparticle Hybrid Materials Sodium cholate does not form gel in water under any condition as compared to other sodium salts of other bile acids such as sodium deoxycholate and lithocholate which show pH-dependent gelation behaviour. Figure 3. Metal cholate hydrogels derived from sodium cholate and a variety of metal ions. In this chapter, super hydrogelation of sodium cholate induced by a variety of metal ions (Ca2+, Cu2+, Co2+, Zn2+, Cd2+, Hg2+ and Ag+) is highlighted with respect to their morphology and mechanical strength/stability. The calcium cholate supramolecular system showed the presence of helically twisted nanofibres which were utilised in the synthesis of soft hybrid materials containing metal (Au and Ag) and metal sulphide (CdS, ZnS, HgS, etc.) nanoparticles. Chapter 4. Cadmium Deoxycholate and Highly Luminescent CdSe Nanocrystals Bile acid derivatives have very high chemical and thermal stability owing to the presence of a rigid steroidal nucleus. We explored the possibility of utilizing the bile salt derived from Cd as a metal complexes as precursor to high quality nanocrystals (NCs) which can only be accessed at high temperatures (>200 oC). Figure 4. Synthesis of high quality CdSe NCs from cadmium deoxycholate. In this chapter, the synthesis of high quality CdSe nanocrystals is discussed using a novel bile acid based precursor: cadmium salt of 7-deoxycholic acid, which has high thermal stability and can be conveniently used at very high temperatures (>300 oC) required for the synthesis of high quality nanocrystals. Syntheses were done both by ‘injection’ and ‘non-injection’ modes. The as-prepared nanocrystals have high photoluminescence quantum yield, multiple excitons, narrow size-distributions and zinc blende/wurtzite crystalline cores. Appendix. Steroidal Thiols in Design of Novel Quantum dot (QD)/Gel Hybrid Materials Bile acid derived steroidal thiols were reported to be efficient capping agents for silver and gold nanoparticles from our laboratory. So, we wanted to check whether they could stabilize the semiconductor nanocrystals as well. Figure 5. Steroidal thiols as stabilizers of semiconductor quantum dots. In this short report, we describe the efficient capping by bile acid derived thiols of group II-VI semiconductor nanocrystals/quantum dots (QDs) (CdS, CdSe). After synthesizing the thiol capped QDs, we tried to disperse the capped nanoparticles into the gel fibres. The hybrid gels showed the presence of nanoparticles inside the fibres as observed by transmission electron microscopy, although the photoluminescence of the QDs was very low in the gel matrix, which might be due to the inefficient surface passivation of the nanoparticles in the gel.

The majority of cancer research projects mainly focus on the epithelial cancer cell, while the role of the tumour stroma has been largely neglected. Conventional 2D techniques, such as well plates and other kinds of tissue culture plastic, and animal models are mainly used to broaden our understanding of how tumours arise, develop, and induce metastasis. However, there is accumulating evidence suggesting a tremendous impact of the non‐cancerous tumour stroma on carcinogenesis, while other publications illustrate the great importance of advanced 3D in vitro models for cancer research. The overall goal of this work was to investigate how cancer associated fibroblasts (CAFs; the most abundant component in the tumour stroma) and normal prostate fibroblasts (NPFs), isolated from patients diagnosed with aggressive forms of prostate cancer, contribute to angiogenesis, an important hallmark of cancer progression. For this purpose, a 3D in vitro angiogenesis co‐culture model was established. At first, two (semi‐) synthetic hydrogel platforms, gelatine methacrylate (GelMA) and star‐shaped (star)PEG‐heparin hydrogels were characterised and their physicochemical properties were compared with each other. Interestingly, GelMA gels shrank while starPEG‐heparin gels swelled in cell culture medium over the course of 24 hours. The cell concentration, in addition to the stiffness, was critical for the formation of endothelial networks, and the knowledge of swelling behaviour enabled the adjustment of initial cell density to ensure the density between both gel types was comparable. Moreover, preliminary tests with mesenchymal stem cells demonstrated that the hydrogel can be actively remodelled, as evaluated by stiffness parameters at day one and seven of incubation. Growth factors (GFs) affect cellular fate and behaviour, and storage, presentation and administration of such chemokines can be critical for certain cellular applications. Due to the high anionic charge density of heparin, starPEG‐heparin hydrogels are known to reversibly immobilise several GFs and thereby might mimic the GF reservoir of the extra cellular matrix. Thus, transport processes of GFs with low and high heparin affinity inside these hydrogels were analysed by fluorescence correlation spectroscopy and a bulk diffusion approach. Results indicated that diffusion constants were synergistically decreased with increasing size and heparin affinity of the diffusant. Next, the capability of endothelial cells (ECs) to self‐assemble and organise into 3D capillary networks was tested in GelMA, starPEG‐heparin and Matrigel hydrogels. Only starPEG‐heparin hydrogels allowed the formation of interconnected capillaries in macroscopic hydrogel samples. However, as it is widely used to test for pro‐ and anti‐angiogenic agents, the 2D Matrigel angiogenesis assay was included for subsequent co‐culture experiments of ECs and fibroblasts in order to investigate how the stromal cells influence the formation of endothelial networks. For a detailed characterisation of 3D structures, a conventionally applied 2D method (Maximum Intensity Projection for 3D reconstructed images, MIP) was compared to an optimised 3D analysing tool. As a result, it was discovered that MIP analysis did not allow for an accurate determination of 3D endothelial network parameters, and can result in misleading interpretations of the data set. Indirect co‐cultures of hydrogel‐embedded ECs with a 2D layer of fibroblasts showed that fibroblast‐derived soluble factors, including stromal cell‐derived factor 1 and interleukin 8, affected endothelial network properties. However, only co‐encapsulation of ECs and fibroblasts in starPEG‐heparin hydrogel discs revealed remarkable changes in endothelial network parameters between CAF and NPF samples. In detail, the total length and branching of the capillaries was increased. For two donor pairs, the diameter of capillaries was decreased in CAF samples compared to NPF samples, underlining the high physiological relevance of this model. In contrast, significant differences in 2D Matrigel assays were not detected between, CAF, NPF and control (ECs only) samples. In summary, a 3D angiogenesis co‐culture system was successfully developed and used to characterise stromal‐endothelial interactions in detail. The combination of advanced biomaterials (starPEG‐heparin) and 3D analysing techniques goes beyond conventional 2D in vitro cancer research, and opens new avenues for the development of more complex models to further improve the acquisition of more biologically relevant data.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Microfluidics covers the science of manipulating small quantities of fluids using microscale devices with great potential in analysis, multiplexing, automation and high-throughput screening. Compared to conventional systems, microfluidics benefits from miniaturization resulting in shortened time of experiments, decreased sample and reagent consumptions as well as reduced overall costs. For microfluidic devices where further weight and cost reduction is additionally required, stimuli-responsive hydrogels are particularly interesting materials since they can convert an environmental stimulus directly to mechanical work without any extra power source. Hydrogels are used as chemostats, micropumps, and chemo-mechanical valves in microfluidics. Existing studies about hydrogels for flow control reported on hydrogels responsive to only one stimulus, including temperature, pH value, and solvent. Combining temperature and pH stimuli within one material is an interesting approach, which allows internal as well as external flow control and broadens potential applications. Among the variety of temperature- and pH-responsive monomers, N-isopropylacrylamide (NiPAAm) and acrylic acid (AA) are considered as ideal building blocks to obtain a hydrogel with pronounced stimuli response. There are different architectures for realizing a temperature- and pH-responsive hydrogel with NiPAAm and AA (e.g. copolymer gels, interpenetrating polymer networks (IPNs), semi-IPNs, or graft copolymer gels). Each approach has its inherent benefits and disadvantages. Grafted hydrogels with a temperature-responsive backbone and pH-responsive graft chains are a promising architecture overcoming drawbacks of copolymer gels (loss of thermoresponsive behavior due to the comonomer), interpenetrating polymer networks (IPNs, difficult fabrication of structured particles via soft lithography), and semi-IPNs (leakage of penetrating polymer). However, studies about multi-responsive grafted hydrogels for flow control in microfluidics are comparatively rare and further research is needed to emphasize their real potential. For this reason, the overall aim of this work was the synthesis of temperature- and pH-responsive grafted hydrogels based on NiPAAm and AA for flow control in microfluidics. This required the synthesis of a pH-responsive macromonomer by RAFT polymerization. As a suitable chain transfer agent with a carboxylic acid group for an end-group functionalization, 2-(dodecyl-thiocarbonothioylthio)-2-methylpropionic (DTP) acid was employed. The approach towards the synthesis of the pH-responsive macromonomer based on two key steps: (i) attaching a functional group, which retains during RAFT polymerization, and (ii) conducting the RAFT polymerization to synthesize the pH-responsive macromonomer. In total, four functionalizations for the macromonomer were investigated, including allyl, unconjugated vinyl, acrylamide, and styrene. End-group analysis and solubility tests revealed that macromonomers with a styrene functionalization are suitable for the synthesis of graft copolymer gels. A series of grafted net-PNiPAAm-g-PAA-styrene hydrogels with a PNiPAAm backbone and PAA-styrene graft chains (Mn = 4200 g/mol, Mw/Mn = 1.6) were prepared and characterized. The main goal was to identify suitable stimuli for an application as a chemo-mechanical valve and to show reversibility of the swelling and shrinking process. Importantly, the temperature sensitivity should be retained, while a pH response needs to be introduced. Equilibrium swelling studies quantified with the response ratio revealed that a grafting density of PAA-styrene between 0.25 and 1 mol-% provides a suitable response towards temperature, pH, salt, and solvent. Furthermore, the swelling and shrinking process is highly reproducible over four consecutive cycles for all four stimuli. In order to evaluate the swelling kinetics of grafted net-PNiPAAm-g-PAA-styrene hydrogels, the collective diffusion model extended by a volume specific surface was applied. The determined cooperative diffusion coefficients of net-PNiPAAm-g-PAA-styrene indicated faster response time with increasing PAA-styrene content. Remarkably, net-PNiPAAm-g-PAA-styrene containing 1 mol-% PAA-styrene exhibited an accelerated swelling rate by a factor of 9 compared to pure net-PNiPAAm. Rheological analysis of net-PNiPAAm-g-PAA-styrene showed that an increasing graft density leads to decreasing mechanical stability. The photopolymerization experiments showed that the gelation time linearly increases with the grafting density. Grafted net-PNiPAAm-g-PAA-styrene hydrogels were tested in two fluidic setups for flow control. A straightforward fluidic platform was developed consisting of a fluid reservoir, an inlet channel, an actuator chamber and an outlet channel. The actuator chamber was filled with crushed hydrogel particles. Accordingly, the fluid flow was directed by the active resistance of the hydrogel particles in the actuator chamber (i.e. swelling degree) and allowed flow control by the local environmental conditions. Flow rate studies showed that the fluid flow throttles when the inlet channel was provided with a solution in which the hydrogel swells (pH 9 buffer solution at room temperature). In contrast, the hydrogel-based valve opens immediately when a solution was used in which the hydrogel collapses. The advantageous properties of net-PNiPAAm-g-PAA-styrene were highlighted by using pH, salt and solvent stimulus in one experiment. Remarkably, the opening and closing function was reversible over six consecutive cycles. As part of a collaboration project with the chair of polymeric microsystems within the Cluster of Excellence Center for Advancing Electronics Dresden (A. Richter and P. Frank), membrane assures hydraulic coupling in a chemo-fluidic membrane transistor (CFMT) and grafted net-PNiPAAm-g-PAA-styrene hydrogels were combined to emphasize the potential of both systems. Flow rate studies showed that 4 different stimuli can be used to control the opening and closing state of the CFMT. Multiple opening and closing cycles revealed no considerable changes in the valve function emphasizing a high potential for an application in microfluidics.

RMN de Exchange em estado sólido é uma importante técnica utilizada na caracterização de processos dinâmicos em ciência dos materiais. Entretanto, a utilização desta técnica no estudo de materiais complexos tem sido limitada. Neste trabalho, serão propostas novas metodologias de RMN de Exchange em estado sólido, que permitem analisar eficientemente movimentos moleculares na escala de tempo de milisegundos. A técnica denominada Pure Exchange Solid-State NMR (PUREX), provê a supressão dos segmentos rígidos dos espectros de exchange, tomando possível observar os segmentos com mobilidade na escala de ms seletivamente. A técnica Centerband-Only Detection of Exchange (CODEX), permite a observação e caracterização de reorientações moleculares lentas com a maior sensibilidade e resolução disponíveis em RMN de estado sólido, através de espectros obtidos sob rotação da amostra em tomo do ângulo mágico (MAS). Utilizando essas técnicas as funções e tempos de correlação e a geometria de movimentos moleculares lentos podem ser determinadas diretamente, sem a necessidade da utilização de modelos que relacionem as grandezas medidas e as características do movimento molecular. A utilização dos métodos apresentados, permite a identificação e caracterização da dinâmica lenta em materiais complexos, tais como polímeros amorfos, semicristalinos e proteínas. Com objetivo inicial de demonstrar as técnicas, elas foram aplicadas para confirmar detalhes da dinâmica molecular em amostras modelo. Através destas técnicas foi possível confirmar a escala de tempo e os ângulos de reorientação envolvidos na dinâmica molecular de cristais orgânicos, Dimetil Sulfona (DMS), e também para revisitar processos de relaxação local em alguns polímeros, polimetacritato de metila (PMMA) e isotatico polipropileno (iPP). As metodologias foram também aplicadas no estudo da transição vítrea em polímeros semicristalinos, isotatico poli(1-buteno) (iPB 1) e sindiotático polipropileno, os quais não tinham sido ainda estudados por técnicas de RMN de Exchange, já que neste caso a maioria dos segmentos moleculares (porção cristalina do polímero) é rígida durante a transição vítrea. Utilizando os métodos CODEX e PUREX os movimentos lentos que ocorrem na região amorfa destes polímeros em temperaturas próximas as suas temperaturas de transição vítrea foram caracterizados. Um estudo dos movimentos lentos que ocorrem em tomo das temperaturas de transição vítrea nas cadeias poliméricas de dois tipos de nanocompostos híbridos siloxano/(polietileno glicol) (ormolitas) também é apresentado. Heterogeneidades nos movimentos das cadeias poliméricas associados com a interação PEG/siloxano foram diretamente observadas através de experimentos PUREX 1D de Exchange 2D. Evidenciais da presença de movimentos de grande e pequena amplitude foram observados para os dois tipos de híbridos. Os resultados revelam que a restrição do movimento das cadeias poliméricas pelas estruturas de siloxano depende tanto do comprimento da cadeia como da natureza das interações entre as fases orgânica e inorgânica do nanocomposto. Finalmente os resultados referentes a caracterização da dinâmica molecular rápida e lenta e sua relação com as propriedades estruturais de um hidrogel protéico são apresentados. Utilizando uma versão modificada da técnica CODEX, juntamente com experimentos de polarização direta, polarização cruzada e RMN de correlação 2D, foi possível não somente confirmar a estrutura e o modelo de formação propostos para o gel, mas também determinar a geometria e a escala de tempo dos movimentos lentos que ocorrem na região de hélice do hidrogel protéico em grandes detalhes. A demonstração teórica e experimental das técnicas e suas aplicações no estudo dessas importantes classes de materiais serão apresentadas. / Solid-State Exchange NMR is an important method to characterize details of dynamic process in materials science. However, the application of these techniques to study complex materials has been limited. In this work new solid-state Exchange NMR techniques, which allows efficient analysis of molecular motions in the millisecond time scale, are presented. The Pure Exchange Solid-State NMR (PUREX) method provides the suppression of the rigid segments in standard exchange spectrum, making possible to observe the slow moving moieties selectively. The Centerband-Only Detection of Exchange (CODEX) technique allows observing and characterizing slow segmental reorientations with the highest available NMR sensitivity and site resolution, in a magic angle spinning (MAS) NMR spectrum. Correlation functions, correlation times and information about the motional amplitude and geometry can be direct1y obtained using the techniques, without any model assumption. These methods allowed identifying and characterizing slow dynamics in complex materials such as, semicrystalline and amorphous polymers and proteins. To demonstrated the proposed techniques they have been applied to confirm some kwon aspect of the slow dynamics of model samples. Using the methods it was possible o confirm the time scale and the reorientation angles involved in the molecular dynamics of organic crystals, Dimethyl Sulfone (DMS), and also to revisit some relaxation process in standard polymers, such as the beta relaxation of poly(methyl metacrylate) (PMMA) and the alfa relaxation in isotactic polypropylene (iPP). The time scale and the geometry of the molecular motions responsible by these relaxation process obtained using the PUREX and CODEX techniques are in excellent agreement with the data taken from the literature, confirming the reliability of the proposed methods. Moreover, the techniques were also applied to study the slow molecular motions involved in the glass transition of semicrystalline polymers, such as isotactic poly (l-butene) form I (iPB1) and syndiotactic Polypropylene (sPP). The glass transition of these polymers had not been studied using Exchange NMR methods because most of the molecular segments (crystalline portion of the polymers) are rigid during the glass transition. Using the PUREX and CODEX methods the slow molecular reorientations within the amorphous region of the polymers were characterized for temperatures near its glass transition. A study of the slow motions occurring around the glass transition temperature in the polymer chains of two types of siloxane/(polyethylene glycol) nanocomposites (ormolites) is also presented. Motional heterogeneities associated with PEG/ siloxane interactions were directly observed in the 13C 1D PUREX and 2D exchange data. Evidences of both small and large angle amplitude motions were direct1y observed for both types of hybrids. The results revealed that the hindrance to the slow molecular motions of the polymer chains due to the siloxane structures depends on the chain length and the nature of the interaction between the organic and inorganic phases. Finally the results concerning the characterization of the fast and slow dynamics and its relationship with the structural properties of a protein hidrogel are presented. Using a modified version of the CODEX technique, together with standard direct polarization, cross polarization and 2D NMR correlation experiments, it was possible not only to confirm the proposed structure and the gel formation model, but also to characterize the geometry and the time scale of the slow motions in the helical domains of the protein hidrogel in great detail. The theoretical and experimental demonstration of all proposed methods and also its applications in these important classes of material will be present.