Poly(N-isopropylacrylamide) (PNIPAM) belongs to a class of stimuli-responsive materials known as “smart” polymers. When cast in the form of a hydrogel, PNIPAM’s lower critical solution temperature (LCST) of 32°C serves as a threshold for volumetric change. For solution temperatures below LCST, PNIPAM hydrogels exist as swollen, hydrophilic networks of polymer and water, spontaneously expelling the bound water molecules to shrink (and become increasingly hydrophobic) as temperature increases beyond LCST. This thesis centers on PNIPAM hydrogel layers grafted along the inner diameter of glass capillaries in order to form a temperature-responsive gating mechanism that spontaneously seals for solution temperatures below LCST. Surprisingly, very thin layers (10-20µm) of PNIPAM have dramatic effects on bulk fluid flow through the capillary due to complex interactions at the swelling interface. Specifically, for the case of capillary pressure driven flow, the swelling PNIPAM interface gives rise to "stick-and-slip" motion for bulk flow. Experiments explore the extent of this phenomenon, while a theoretical framework is proposed to model how the evolving gel interface pins the contact line. Additionally, an exploratory segment of this work examines the ways in which PNIPAM hydrogel nanoarrays can be synthesized via scalable template methods. Nanostructured PNIPAM films exhibit dramatic changes in surface properties with temperature, characterized by very low contact angles (~10°) below LCST, and very high ones (~160°) above LCST. Results for several methods are presented with lessons learned to guide future development of surfaces with temperature-responsive wetting properties.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Diabetic foot ulcers (DFUs) are a common and severe adverse event associated with diabetes, as 25% of diabetic patients will experience DFUs. The lack of effective DFU therapies results in 20% of diabetic patients requiring amputation. We first developed an algorithm to account for polydispersity when calculating nanoparticle concentration, which will reduce variability between batches and treatments. We also developed a novel 2-layer biomaterial, which combines anti-microbial properties of CLKRS peptide coated silver nanoparticles (CLKRS- AgNPs) with a pro-regenerative collagen matrix embedded with microscopic skin tissue columns (MSTC), to promote DFU wound healing. The collagen hydrogel formulation was optimized, and the physical properties, biocompatibility, and wound healing properties were assessed. Our results indicate that the CLKRS-AgNPs prevent bacterial growth and the collagen matrix provides a regenerative environment. Last, we developed and tested antimicrobial fabrics which can also be applied to chronic wounds, such as DFUs, to prevent and treat infections.

Estima-se que os EUA gastem por ano cerca de 100 milhões de dólares anuais para tratar e reabilitar pacientes com doenças na coluna vertebral. Aproximadamente 15% dos pacientes que são operados da coluna vertebral, não obtêm melhora clínica e irão necessitar de outros procedimentos cirúrgicos. Entre as principais causas de insucesso nos procedimentos cirúrgicos da coluna vertebral está a fibrose epidural, também chamada de peridural, e a utilização de um de material inibidor desta fibrose, nesse tipo de cirurgia, vem sendo pesquisada, mas até o momento não existe nenhum produto comercial, nacionalmente produzido, destinado à prevenção desta fibrose. O objetivo deste trabalho foi o desenvolvimento e caracterização químico-física e microbiológica de um hidrogel à base de Carboximetilcelulose de sódio (NaCMC) e própolis. Foram preparados 4 géis de NaCMC e própolis (1%, 2% e 8% e ausência de própolis) e caracterizados através da espectroscopia vibracional na região infravermelho, microscopia eletrônica de varredura e também teste microbiológico. A espectroscopia vibracional da região do infravermelho identificou a formação de banda característica da ligação própolis com carboximetilcelulose de sódio. A estrutra microscópica manteve-se inalterada, mesmo na concentração de 8% de própolis. O gel de NaCMC própolis 8% demostrou possuir excelente atividade antimicrobiana em relação aos demais géis e abre novas possibilidades de trabalhos futuros in vivo que poderão fornecer informações sobre a eficácia antiaderente e sua possível aplicação em procedimentos neurocirúrgicos. / It is estimated that the United States annually spend around 100 million dollars annually to treat and rehabilitate patients with spinal diseases. Approximately 15% of patients who are operated on the spine, does not obtain clinical improvement and will require other surgical procedures. Among the main causes of failure in surgical procedures of spinal epidural fibrosis is also called the epidural and the use of an inhibitor material of fibrosis in this type of surgery, has been researched, but so far there is no commercial product, nationally produced, for the prevention of fibrosis. The objective of this work was the development and characterization and chemical-physical microbiological analysis of a hydrogel made of NaCMC and propolis. Gels were prepared in four NaCMC and propolis (1%, 2% and 8% and the absence of propolis) and characterized by infrared vibrational spectroscopy, scanning electron microscopy and also microbiological testing. The vibrational spectroscopy identify the characteristic of propolis connection with carboxymethylcellulose. The structure microscopic remained unchanged, even at a concentration of 8% propolis. The NaCMC gel 8% propolis have demonstrated excellent antimicrobial activity compared to other gels and opens new possibilities for future work in vivo that might provide information on the effectiveness nonstick and its possible application to neurosurgical procedures.

O estudo da distribuição e propagação a luz em tecidos biológicos é importante para diversas aplicações em fototerapias e diagnóstico. Os tecidos biológicos são considerados meios túrbidos, onde existe uma combinação de absorção e espalhamento, e a determinação do comportamento da luz dentro deles tem sido estudado através da aplicação de modelos que tem suas limitações. Então, determinar e manipular a distribuição para entrega da melhor dose de luz é crucial para o sucesso dos tratamentos. Para casos de Terapia Fotodinâmica, em particular, os tratamentos de lesões planas lisas, em grande parte dos casos, são bem sucedidos. Este sucesso deve-se ao fato de que existe uma boa possibilidade de distribuição uniforme da luz dentro do tecido da lesão tratada. Por outro lado, para tumores espessos de superfícies irregulares, a iluminação é dificultada devido à presença de sombras, rachaduras entre outras imperfeições sobre a lesão. Deste modo, a entrega da dose de luz inadequada e a iluminação não homogênea, resultam em regiões de necroses parciais e recidiva. Portanto, é decisivo melhorar o perfil da distribuição dentro do tecido. Neste trabalho avaliamos o acoplamento da luz utilizando um gel posicionado entre a fonte ( &#955= 630 nm) e a superfície de um phantom sólido. O acoplamento do feixe foi melhorado incorporando baixas concentrações de espalhadores ao gel. Imagens do perfil de distribuição da luz foram coletadas e transformadas em matrizes de intensidades, e posteriores curvas de isointensidades. Nossos resultados mostraram uma grande melhora na uniformidade da distribuição. De fato, utilizando um meio acoplador, conseguimos entregar um feixe mais homogêneo promovendo uma melhor iluminação. Esta técnica elimina drásticamente os efeitos da rugosidade da superfície do phantom dentro do volume tratado. Acreditamos que esse trabalho mostra uma possibilidade de melhora na dosimetria para fototerapias. / The light propagation and distribution studies in biological media are importante for several phototherapy and diagmostic aplications. The biological tissues are considered turbida medias, where there is absortion and scattering combination, and determinate the light behavior inside this tissues have been studied by models that has some limitations.Then, to determine and control the light distribution to improve the light dose delivery is important for the treatment successful. For particular cases, such as Photodynamic Therapy (PDT) applied on smooth planar lesions treatments is appropriated, since there is a good possibility of uniform distribution of light within the tissue of the treated lesion. On the other hand, tumors with more thickness may not receive the needed doses of energy to cause its death. For an efficient treatment by photodynamic therapy is required an optimal coupling light inside the lesion tissue. Shadow effects, slits or physical irregularities in the lesion can lead a nonhomogeneous light distribution inside the tissue. The results can be a partial necrosis regions and tumor recurrence. Therefore it is crucial improving the light profile inside the tissue to overcome these problems. In this study, we measured the light profile inside the phantom after the light passing through a gel as coupler. We used a solid phantom as biological tissue model and was used a red laser (&#955 = 630 nm) as light source with an optical fiber to direct illumination. The coupling is controlled by introducing a gel with low concentration of scatters between the fiber and de phantom. Was collected pictures of light profile with a camera and the data were processed with MatLab software. Our results shows a strong improvement in the light distribution when the gel with scatters is positioned between fiber and tissue. In fact, a more homogeneous laser bean is delivered to tissue promoting a better light distribution. This technique eliminates drastically the roughness effect of the phantom surface in the bulk. We believe that this work shows a possibility of dosimetry improvement for phototherapy.

The use of low-molecular weight peptide-based hydrogelators (LMWGs) for the immobilisation of enzymes is presented in this thesis. Low-molecular weight hydrogelators are a class of materials which are highly suitable for increasing enzyme lifetimes as they create a suitable biomimetic environment. Immobilised enzymes can be utilised in enzyme fuel cells, providing low-energy conversion routes for chemical processes. The hydrogels also possess tunable properties which allow their structure to be manipulated to give desirable properties. This work begins with an exploration of dipeptide hydrogelators by investigating the effect of varying salt solutions and concentrations of dipeptide on final hydrogel structures. A wide range of characterisation techniques are employed to provide information about the micro- and macro-structure of the hydrogels. The creation of dipeptide hydrogel materials via an electrochemical method is explored, which allows the production of nanometre thick, membrane-like materials. These layers are measured using Surface Plasmon Resonance techniques. The electrochemical technique for dipeptide gelation is expanded in later chapters to produce a range of novel materials. Finally, an exploration into the effect of additives on dipeptide hydrogels is conducted, where the effect of adding chiral molecules is investigated. This provides interesting information regarding the self-assembly processes involved with hydrogelation processes, which has important implications for studying the folding and unfolding processes of peptides.

"In this thesis, a cell traction force microscopy method is developed for measuring traction forces of connective tissue cells. This method includes an improved methodology in traction force microscopy of live cells cultured on an elastic substrate. Tissue cells, such as skin and muscle cells respond to the mechanical stimuli of their microenvironment by adhering to their substrate and exerting forces on the proteins of the extracellular matrix (ECM). These forces are called cell traction forces. Fibroblasts are grown on polyacrylamide (PA) gels embedded with fluorescent beads and coated with different types of ECM ligands. Traction forces of NIH 3T3 fibroblasts are calculated from the measured deformations of PA gels by using a 3-D finite element method. The advantages of this method compared to the traditional methods of cell traction force microscopy (CTFM) are that this method takes into account the finite thickness of the substrate by applying a 3-D FEM analysis to reduce the errors of using an infinite half space approximation for a substrate with a finite thickness and that it uses a novel method for embedding the substrate with fluorescent markers that decreases the measurement uncertainties. In our approach fluorescent beads were embedded on the top of substrate instead of getting mixed with the gel. This decreases the effect of out-of-focus fluorescent beads on the measured deformation fields which enhances the accuracy of cell traction force measurements."

No description available.

Philosophiae Doctor - PhD / Persistent root canal pathogens are one of the main causes of endodontic treatment failure. These pathogens are usually isolated in areas within the root canals that are inaccessible to mechanical instrumentation, chemical irrigants and medicaments resulting in incomplete sterilization of the root canal system. Furthermore, the development of resistant microbial species renders it difficult to disinfect the root canal system using commonly available root canal irrigants and intra-canal medicaments. Intra-canal medicaments are antimicrobial agents that are placed inside the root canal system in order to eliminate the remaining microorganisms that persist after mechanical instrumentation and irrigation. However, their antimicrobial efficacy is effective only against some of the root canal pathogens. Furthermore, the presence of tissue inhibitory factors such as dentine powder and serum albumine within the root canal system inhibits their antimicrobial activity. The use of nanoparticles as antimicrobial agents has recently attracted considerable attention especially in the medical field as a result of their unique antibacterial properties. These properties include their ability to use multiple mechanisms to eradicate microbial cells and their low potentiality to produce microbial resistance. Polymeric nanoparticles such as chitosan nanoparticles (Ch-Np) gained significant interest as a result of their biocompatible and antimicrobial properties. In medicine, several vehicles were designed to carry these antibacterial nanoparticles. Zeolites (Ze) are microporous crystalline hydrated sodium aluminosilicate material that is utilized in the chemical sciences as a carrier for various nanoparticles.

Controlled hydrogel dissolution allows for: 1) atraumatic material removal after it served its function, 2) site-specific delivery of encapsulated therapeutics (e.g., proteins, small molecules), and 3) a tailored administration of an agent with high efficiency. Dissolution of covalently crosslinked hydrogels has been accomplished by incorporating cleavable moieties that undergo ester hydrolysis or enzymatic degradation. Recently, thiol-disulfide exchange, retro Michal-type reactions, retro Diels-Alder reactions, and thiol-thioester exchange chemistries have gained attention, as they provide a responsive synthetic handle for engineering hydrogel dissolution rates. We synthesized, characterized and tested in vivo two on-demand dissolvable dendritic thioester hydrogel dressings for second-degree burn care and hemorrhage control. The hydrogels are composed of lysine-based dendrons and PEG-based crosslinkers, which were prepared in high yields. In context of hemorrhage, there is an unmet clinical need for an on-demand dissolvable sealant for non-compressible hemorrhage or areas of body not amenable to treatment with a torniquet. In a model of in vivo hemorrhage control of intra-abdominal wounds, our hydrogel reduced blood loss by 33% in severe hepatic hemorrhage and by 22% in aortic injury, as compared to untreated controls. There is an unmet clinical need for a second-degree burn dressing that can be removed atraumatically and serve as a barrier to bacterial infection. When our hydrogel was used as a dressing, local and systemic bacterial proliferation after wound contamination was significantly lower than in the untreated group. The total bacterial burden of the burn wound in the positive controls was significantly higher than in the hydrogel group and the negative controls (1.39x10E8 ± 8.30x10E7 CFU/g v. 4.04x10E3 ± 3.99x10E3 CFU/g v. 6.88x10E2 ± 6.38x10E2 respectively; P = 0.009). Also, the total systemic bacterial burden in the positive controls was significantly higher than the hydrogel group and the negative controls (9x10E2 ± 7.76x10E7 CFU/g v. 5x10E1 ± 0 CFU/g v. 5x10E1 ± 0 CFU/g, respectively; P = 0.031). A unique feature of both hydrogel systems is their capability to be dissolved on-demand via thiol-thioester exchange reaction with a biocompatible solution following its initial application – thus the wound area can be re-exposed to allow for definitive surgical care.