No description available.

The main objective of the present work was to explore the self-organisation ability of the multiblock copolymers to form injectable reversible hydrogels and especially to answer to the question how the block copolymer topology affects the gelation efficiency / Ο κύριος σκοπός της παρούσσης δουλειάς ήταν να εξερευνήσουμε την ικανότητα αυτοοργάνωσης του πολυσυσταδικού συμπολυμερούς να σχηματίσει εμβόλιμο αναστρέψιμο υδροπήκτωμα και να απαντήσει στο ερώτημα πως η τοπολογία του συσταδικού συμπολυμερούς επηρεάζει την αποδοτικότητα της δημιουργίας πηκτώματος

The major topics discussed are all relevant to interfacing brightly phosphorescent and non-luminescent coinage metal complexes of [Ag(I) and Au(I)] with biopolymers and thermoresponsive gels for making hybrid nanomaterials with an explanation on syntheses, characterization and their significance in biomedical fields. Experimental results and ongoing work on determining outreaching consequences of these hybrid nanomaterials for various biomedical applications like cancer therapy, bio-imaging and antibacterial abilities are described. In vitro and in vivo studies have been performed on majority of the discussed hybrid nanomaterials and determined that the cytotoxicity or antibacterial activity are comparatively superior when compared to analogues in literature. Consequential differences are noticed in photoluminescence enhancement from hybrid phosphorescent hydrogels, phosphorescent complex ability to physically crosslink, Au(I) sulfides tendency to form NIR (near-infrared) absorbing AuNPs compared to any similar work in literature. Syntheses of these hybrid nanomaterials has been thoroughly investigated and it is determined that either metallic nanoparticles syntheses or syntheses of phosphorescent hydrogels can be carried in single step without involving any hazardous reducing agents or crosslinkers or stabilizers that are commonly employed during multiple step syntheses protocols for syntheses of similar materials in literature. These astounding results that have been discovered within studies of hybrid nanomaterials are an asset to applications ranging from materials development to health science and will have striking effect on environmental and green chemistry approaches.

No description available.

No / Stem cells are known to differentiate in response to the chemical and mechanical properties of the substrates on which they are cultured. Thus, supramolecular biomaterials with tunable properties are well suited for the study of stem cell differentiation. In this report, we exploited this phenomenon by combining stem cell differentiation in hydrogels with variable stiffness and metabolomics analysis to identify specific bioactive lipids that are uniquely used up during differentiation. To achieve this, we cultured perivascular stem cells on supramolecular peptide gels of different stiffness, and metabolite depletion followed. On soft (1 kPa), stiff (13 kPa), and rigid (32 kPa) gels, we observed neuronal, chondrogenic, and osteogenic differentiation, respectively, showing that these stem cells undergo stiffness-directed fate selection. By analyzing concentration variances of >600 metabolites during differentiation on the stiff and rigid gels (and focusing on chondrogenesis and osteogenesis as regenerative targets, respectively), we identified that specific lipids (lysophosphatidic acid and cholesterol sulfate, respectively), were significantly depleted. We propose that these metabolites are therefore involved in the differentiation process. In order to unequivocally demonstrate that the lipid metabolites that we identified play key roles in driving differentiation, we subsequently demonstrated that these individual lipids can, when fed to standard stem cell cultures, induce differentiation toward chondrocyte and osteoblast phenotypes. Our concept exploits the design of supramolecular biomaterials as a strategy for discovering cell-directing bioactive metabolites of therapeutic relevance.

Hydrogels have attracted interest as biomaterials due to their similarity to native tissue and extracellular matrix as well as their versatility and tunability. Each of these characteristics allows hydrogels to be used in a wide variety of biomedical applications including drug delivery, tissue engineering, and regenerative medicine. Poly(oligoethylene glycol methacrylate) (POEGMA) has been shown to possess attractive biological and thermoresponsive properties, serving as an alternative to both poly(ethylene glycol) (PEG) and poly(N-isopropylacrylamide) (PNIPAM) depending on the number of ethylene oxide repeat units in the POEGMA side chain. Our group has shown the versatility of POEGMA and has successfully developed hydrazide- and aldehyde-functionalized polymer precursors that form an injectable in situ gelling hydrogel. By engineering the precursor polymer structure and crosslinking density (i.e. number of reactive functional groups in the precursor polymers), the properties of these hydrogels can be tuned. Herein, a hyperbranched structure was incorporated into POEGMA precursors to control the physical and biological properties of hydrogels independent of the chemistry while maintaining gel injectability. By varying the degree of branching (DoB) in these precursors, it was possible to tune the hydrogel properties based on reacting combinations of hyperbranched-linear and hyperbranched-hyperbranched precursor polymers. While it was feasible to tune the mechanical properties of the hyperbranched hydrogels based on the DoB, the hyperbranched-hyperbranched system showed diminished mechanical strength when compared to the hyperbranched-linear system. Overall, the mechanical properties of the whole hydrogel series were comparable to previously reported linear POEGMA hydrogels. In terms of swelling and degradation kinetics, the swelling and degradation rate in both acid-catalyzed conditions and in phosphate-buffered saline (PBS) at physiological temperature (37°C) correlated with DoB and polymer size. The precursor polymers showed minimal cytotoxicity in the presence of 3T3 mouse fibroblasts. Lastly, each of the hyperbranched hydrogels adsorbed higher quantities of protein compared to PEG-based hydrogels, but still relatively low amounts compared to other polymeric biomaterials. We have shown that it is possible to significantly tune the physicochemical properties by slightly changing the polymer precursor chemistry, namely by varying the amount of crosslinker and, thus, the degree of branching in the polymer network. Therefore, hyperbranched POEGMA offers a versatile platform to create tunable hydrogels based on polymer precursor structure for biomedical applications. / Thesis / Master of Applied Science (MASc)

Bacteriophages (phages) are bacterial viruses. Phages offer remarkable diversity and can be found in many shapes and sizes; however, what they all have in common is that they are made of protein nano-shells that encase their genome (DNA or RNA). In other words, phages are proteinous bionanoparticles. In this work, we use the filamentous phage M13. M13 is a simple virus with a high aspect ratio. It has 11 genes and only 5 structural proteins. The phage filament is almost entirely made of 2700 copies of pVIII, the major coat protein, and is capped off on one end by five copies each of the proteins pIII and pVI, while the opposite end displays five copies each of the proteins pVII and pIX. M13 phage can be genetically engineered to display certain peptides with affinity toward cancer cells, specific tissue, or even minerals and polymers. These filaments can further self-organize to form liquid crystals at high concentrations. All these properties make M13 a unique building block for the bottom up synthesis of advanced bioactive material. The objective of my proposed research is to develop hydrogels using M13 phage. Hydrogels can absorb large quantities of water without dissolving. They mark a breakthrough in the field of biomaterials, owing to their high water content, porosity and soft consistency. I crosslinked M13 at liquid crystalline concentrations using glutaraldehyde. The resulting hydrogels were characterized for swelling and mechanical properties. These hydrogels exhibited self-healing and autofluorescence properties. In addition, I demonstrated that M13 can from self-healing hydrogels at lower concentrations by adding the small globular protein, BSA. The developed M13 hydrogels mark the first step in the development of bioactive hydrogels that could be utilized to direct cell destiny and genuinely mimic the natural tissue. / Thesis / Master of Applied Science (MASc) / Filamentous phage are viruses that infect bacteria. These bio-filaments are ~1 𝜇𝑚 long, 6-8 nm in diameter and can propagate themselves by infecting bacteria. This means one bio-filament can make 300-1000 particles only by infecting a bacterial host, a characteristic that drastically increases their utility over synthetic filamentous nanomaterial. Filamentous phage can be readily genetically engineered to express foreign receptors on their surface. In this thesis, I demonstrate how these bio-filaments can self-organize at high concentrations and can be crosslinked to make hydrogels that can adsorb up to 12 times their weight in water. These hydrogels can also heal themselves if broken or cut and exhibit autofluorescence, which are very useful properties for hydrogels used for biomedical applications. We further demonstrate that adding small proteins to the bio-filaments can expand the range of hydrogel formation, to the extent that even low concentrations of bio-filament can form hydrogels.

Mammals secrete fluids from the sweat glands known as perspiration which helps in thermoregulation. However, sweat can interfere with vision, comfort, grip, and results in malodor due to bacterial action. To combat the aforementioned issues, antiperspirants are widely used personal hygiene products to stop the sweat by blocking the sweat glands. Typically, aluminum salts present in the antiperspirants dissolve in the sweat and create a temporary plug to cut the flow of sweat. However, there has been a long debate going on the safety concerns of aluminum-based antiperspirants. Although there is no concrete evidence to prove the carcinogenicity of aluminum, various studies have also shown that long exposure to aluminum can lead to breast cancer in women. Hence there is a potential need to find aluminum-free alternatives for antiperspirants. Consumers are also showing an increased demand for more natural cosmetic products. The current study presents a novel aluminum-free the hygroscopic gel which can potentially serve as an antiperspirant. A synthetic sweat duct has been developed to mimic the sweating behavior of humans and to test the synthesized gels. Hygroscopic materials readily absorb and/or adsorb water from a humid environment. The hygroscopic gel can cause long-range evaporation of water from the sweat leading tocrystallization of minerals which can ultimately clog the sweat duct and prevent sweating. / Master of Science / We secrete water-like fluid known as sweat which helps us cool down our body. Sweating is also common when we are in the situation of high stress, anxiety, or excitement as a reaction from the body. However, sweating can be disgusting when it results in bad odor or when our armpits look wet. It can also affect our grip, vision, and comfort. Hence we use antiperspirants to stop the sweat and get rid of various issues caused by sweat. These antiperspirants usually have aluminum salts which dissolve in sweat and makes a gel. This gel then clogs our sweat glands and we stop sweating. However, many scientists argue that the presence of aluminum salts in the body can lead to cancer. Although many scientists have also shown that the aluminum salts are completely safe, it is not completely clear. The yellow stains we see on the shirts near the sleeves are also due to these aluminum salts. These days, consumer is also very particular about the contents of the products being used and nobody wants to put any external chemicals inside the body. Here, we present a hydrogel, which is aluminum free and can serve as an alternative to aluminum-based antiperspirants. These hydrogels have a strong affinity to water and can even evaporate nearby water. Hence these hydrogels can be used to evaporate the water from the sweat and causing the salts present in the sweat to crystallize. These naturally present salts in the body can thereby cause the clogging of the sweat duct. Once clogged, it should stop sweating and keep us dry without worrying about safety concerns of aluminum salts.

Face à l’apparition croissante de troubles pigmentaires liés à l’exposition aux UV, le développement de nouveaux actifs blanchissants représente un enjeu majeur pour l’industrie cosmétique. De plus en plus de consommateurs s’orientent vers des produits eco-responsables, il devient urgent de développer de nouvelles méthodes de biocatalyse pour accéder à des antipigmentants. Certains glycosides, comme l’arbutine présentent des propriétés blanchissantes qui restent toutefois limitées face à l’hydrolyse rapide de la liaison O-glycosidique. L’enjeu du projet consiste à synthétiser des analogues de cette molécule en série thioglycosidique. En effet, cette liaison permet une plus grande stabilité vis à vis de l’hydrolyse. La mutation d’une glycosidase native issue de dictyoglomus thermophilum a permis d’accéder à une thioglycoligase. Cette dernière permet d’obtenir par catalyse enzymatique des analogues de l’arbutine. Six composés en série S- et O-glycosidique ont pu être synthétisés et testés en tant qu’agents dépigmentants. La méthodologie de synthèse a ensuite été appliquée pour l’obtention de thioglycolipides. Ces molécules sont connues pour leurs propriétés hydrogélifiantes permettant d’accéder à des matériaux thermoreversibles. Cinq molécules ont été identifiées en tant qu’agents hydrogélifiants. Les propriétés rhéologiques, thermiques et structurales ont été caractérisées mettant en évidence des différences significatives parmi les composés. Enfin les résultats préliminaires sur la formulation d’un produit à la fois antipigmentant et texturant s’avèrent prometteurs pour la validation d’un concept de matériau intelligent pour l’industrie cosmétique. / Considering the increasing appearance of pigmentation disorders caused by UV exposure, the development of new whitening agents is a major challenge for the cosmetics industry. Consumers are turning to ecoresponsible products, it is urgent to develop new methods of biocatalysis for the access to new depigmenting agents. Some glycosides, such as arbutin, have whitening properties which are still limited because of therapid hydrolysis of the O-glycosidic bond. The challenge of this project is synthesize analogues of this molecule in thioglycoside series. Endeed, this bond allows a greater stability against the hydrolysis. The mutation of anative glycosidase to dictyoglomus thermophilum gives access to a thioglycoligase. This makes possible the enzymatic synthesis of arbutine analogues. Six molécules were synthesized and tested as depigmenting agents. The synthesis methodology was then applied to the preparation of thioglycolipids. These moleculesare known for their hydrogellating properties allowing access to thermoreversible materials. Five molecules have been identified as hydrogellating agents. The rheological, thermal and structural properties have been characterized and showed significant differences depending of the compound structure. Lastly, the preliminary results on the formulation of a product that is both antipigmenting and texturizing are promising for the validation of an smart material concept for the cosmetic industry.

Polymeric hydrogels were used to create bio-smart hydrogels serving multifunctional roles interfacing with cells and enzyme substrates. Their value lies in their use as: i) Stimuli- responsive membranes that directly transmute chemical potential energy into proportionate electrical signals, ii) as biomimetically inspired biocompatible coatings on stents and other implantable bionic devices, iii) as bio receptor hosting membranes for enzyme-based implantable biosensors. Biosensors use oxidoreductase enzymes such as glucose oxidase (GOx) and lactate oxidase (LOx) to confer specificity. Such enzymes may initiate more complex in vivo inflammatory response. In this thesis individual and combined effects of different enzymes (GOx, Superoxide dismutase (SOD), and catalase) were studied to achieve hydrogelenzyme systems, which in theory may mitigate against adverse cell outcomes. The incorporation of enzymes into bioactive hydrogels was investigated, and revealed effects on the growth, viability and attachment of surface dependant RMS13 human muscle fibroblasts and B50 rat neuronal cells. Agarose and p(HEMA)-based hydrogels were prepared with fibrinogen 5% (w/v) to promote integrin-mediated cellular attachment and also with different combinations of glucose oxidase (GOx), catalase (CAT) and superoxide dismutase (SOD). Cell viability was maintained best on catalase hydrogels. The presence of GOx within hydrogels membrane compromised cell viability in both hydrogel types, presumably due to accumulation of H2O2 confirmed by amperometric detection using fabricated platinum needle electrodes. Hydrogels prepared with GOx and CAT showed improved cell viability, further suggesting the negative influence of H2O2. High temperature treatment of the enzyme-hydrogel membranes, resulting in enzyme denaturation, returned all constructs to control levels of viability, confirming the relationship of cell viability with enzyme activity. An additional study was undertaken into the viability and growth of B50 cells on crosslinked protein membranes of fibrinogen and albumin as a potential bioreactor surface. The use of crosslinked fibrinogen to facilitate cell growth within microfluidic channels appears to have been realized. Fabrication and use of miniaturized gold-filled silica recess and inlaid disc electrodes, compared with the use of agarose gels in the recesses was investigated to improve stabilization of an amperometric H2O2 electrode. From this, a microfluidic device with an integrated inner diameter working and counter / reference electrode was fabricated which showed feasibility of more rapid amperometric detection of H2O2 in miniature flow channels.