Chapter 1: Luminescence property of lanthanide and its applications Lanthanides are well-known for their unique luminescence property and have found widespread applications in sensing, bioimaging, lasers, optoelectronic devices, etc. Due to Laporte forbidden f-f transitions, lanthanides have very low intrinsic emission. The problem can be overcome by use of an ‘antenna’, which is an organic chromophore with excited state energy higher than the lanthanides’ emitting levels. Thereby it is possible to get highly emitting lanthanide complexes through energy transfer from the ‘antenna’. Due to long lifetime of lanthanides’ excited states, it's possible to perform time delayed measurement which is useful in bioassays and bioimaging since the short-lived background emission is effectively filtered. Research in supramolecular metallogels has grown rapidly in recent years, and already proven to have potential for designing advanced materials for a variety of applications, such as sensing, optoelectronics, catalysis, nanoparticle synthesis, biomedicine etc. A supramolecular gel where a lanthanide is an integrated part of it can combine the advantages of the supramolecular gel along with the unique property of lanthanide luminescence and thus such materials can be explored for potential applications. This chapter discusses the background information on the unique luminescence of lanthanides, and some examples of the applications of lanthanide complexes and lanthanide based gels. Chapter 2: Lanthanide luminescence based enzyme sensing in hydrogels This chapter describes the use of Tb/Eu luminescence in the sensing of biologically important enzymes. We discovered the sensitization of Eu(III) in Eu-cholate gel by 1-hydroxypyrene, and of Tb(III) in Tb-cholate gel by 2,3-dihydroxynaphthalene. These two sensitizers were covalently modified and sensitizer-appended hybrid (artificial) enzyme substrates were prepared for a few biologically important hydrolases. The covalently modified sensitizer termed as “pro-sensitizers”, didn't sensitize Tb(III)/Eu(III) in the hydrogel and no photoluminescence was observed. In the presence of the appropriate enzyme in the hydrogel, the pro-sensitizer was cleaved to liberate the sensitizer, which led to an enhancement of luminescence with time. Alkaline phosphatase and β-lactamase were assayed using pyrene phosphate and pyrene-oxo-cephalosporanic acid derivatives, respectively, in Eu-cholate hydrogel (Figure 1). β-Galactosidase was assayed using Tb(III) luminescence in Tb-cholate gel. The enzyme detection was based on red/green luminescence response from the gel. To understand the behaviour of the enzymes in the hydrogel, kinetic parameters were determined. The detection of different enzymes was also demonstrated in natural/biological samples like blood serum, milk and almond extract. Figure 1. Three different pro-sensitizers used for alkaline phosphatase, β-lactamase and β-galactosidase assays Chapter 3: Enzyme sensing on paper discs using lanthanide luminescence Developing a user-friendly biosensor is of considerable importance in clinical and analytical chemistry. Paper based biosensor design is an emerging field of research and paper based point of care (PoC) testing devices have already found applications in clinical, veterinary, environmental, food safety, security etc. Paper is made out of natural cellulose fibres, and has advantages of low cost, biodegradability, biocompatibility, and user friendliness. Paper based sensors have been used for the detection of ions, glucose, proteins, nucleic acids, antigens etc., with mostly colorimetric, fluorescent, electrochemical, chemiluminescence and Electrochemiluminescence readouts. In this work, the non luminescent Tb(III) and Eu(III) were embedded on paper as their cholate hydrogels and were used for detecting different hydrolases. Pro-sensitizers, as reported in Chapter 2, were immobilized on paper for the detection of a specific enzyme. The “pro-sensitizer” released the sensitizer upon enzyme action and led to luminescence enhancement from the gel coated paper disc. By this way, four different hydrolase enzymes detection were carried out using Tb(III)/Eu(III) luminescence as the readout (Figure 2) and the practical utility was demonstrated by the detection of specific enzymes in natural/biological samples. This paper disc based enzyme sensing provides a simpler and user friendly approach over the contemporary approach of enzyme sensing typically carried out in solution. Figure 2. Paper based biosensors for hydrolase enzymes Chapter 4: Luminescence resonance energy transfer in self-assembled supramolecular hydrogels Luminescence resonance energy transfer is a phenomenon of energy transfer between a FRET (Förster resonance energy transfer) pair, where a lanthanide is the donor. Lanthanides have attracted attention for the last several decades for their unique luminescence properties. LRET is a FRET process along with added advantages of Lanthanides, i.e. long lifetime of the lanthanides and characteristics emission spectra. LRET has been used for studying interaction of biomacromolecues, immunoassay, bioassays, etc. LRET in either a supramolecular organogel or a hydrogel is still an unexplored field. In this work we showed the energy transfer from Tb(III) to two different red emitting dyes in Tb-cholate hydrogel (Figure 3). The self assembly processes during hydrogelation assisted the energy transfer process without any need for laborious synthesis. The energy transfer was confirmed by time delayed emission, excitation spectra and lifetime measurement in the hydrogels. Energy transfer was observed both in the gel and the xerogel states. These luminescent materials may find applications in optoelectronics. Figure 3. Energy transfer from DHN to Tb3+ and then to red emitting dyes (Rhodamine B & Sulforhodamine 101) in the Tb-Cholate hydrogel Chapter 5: Room temperature synthesis of Lanthanide phosphate nanoparticle using a gel as a soft template Lanthanide orthophosphates are an important class of rare earth compounds, and have widespread applications in laser materials, optical sensors, heat resistance materials, solar cell etc. There are several methods in the literature for the synthesis of rare earth phosphate nanoparticles. Most of these are based on hydrothermal, microwave assisted, micro emulsion, arrested precipitation etc., which invariably dependent on stringent conditions such as (i) high temperatures and pressures, (ii) inert atmosphere and (iii) the use of external capping agents as stabilizers. Synthesis of such nanoparticles under milder conditions would always be preferable. In this context, the preparation of nanoparticles using hydrogel as template can be a possible alternative approach. The LnPO4 nanoparticle synthesis was done by diffusion of Na3PO4 in Ln-cholate hydrogels. The particles were characterized by transmission electron microscopy (TEM) and powder XRD analysis. TEM showed the formation of 3-4 nm size particles with an ordered arrangement on the gel fibre. This work demonstrated that the lanthanide cholate gels have high potential for the synthesis, and immobilization of lanthanide phosphate nanoparticles at room temperature to produce new types of composite materials. (For structural formula pl see the abstract pdf file)

L'objectif principal de cette thèse est d'apporter une contribution à la modélisation de la cinétique de libération de principes actifs à partir de systèmes polymère-médicament, en tentant de réduire le "burst effect" et augmenter le temps de libération. L'idée de base est, dans un premier temps, l'encapsulation du médicament dans des liposomes, vésicules lipidiques capables de transporter le médicament, puis son inclusion dans des hydrogels polymères de manière à créer deux barrières dans le processus de libération du médicament. Les hydrogels sont à base de chitosane/gélatine et chitosane/poly(alcool vinylique) réticulés, partiellement avec de l'aldéhyde glutarique et de manière prédominante par voie ionique avec des anions sulfate ou polyphosphate. Une seconde catégorie est à base de chitosane, seul ou en combinaison avec le poly(alcool vinylique), réticulé avec de l'acide tannique à travers de nombreuses interactions hydrogène. Les hydrogels sont caractérisés d'une part par leur structure, leur morphologie, leur comportement en milieu aqueux et leur stabilité thermique; d'autre part leurs propriétés comme biomatériau (hémocompatibilité et cytotoxicité), leur capacité à inclure et libérer un composé modèle (la calcéine) libre ou encapsulé dans des liposomes. La dépendance de ces propriétés (gonflement, libération des composés solubles inclus) avec les paramètres du processus de préparation (quantité de réticulant, rapport ente les polymères utliisés, masse molaire du chitosane) est établie. Les études de cinétique de libération de la calcéine (incluse direment dans les hydrogels ou encapsulée dans les liposomes dispersés ensuite dans les hydrogels) prouve la pertinence de l'hypothèse de départ: quel que soit le type de réticulation employée pour la préparation des hydrogels, la libération de la calcéine à partir des systèmes complexes (hydrogel-liposomes-calcéine) est fortement retardée sans manifester de "burst effect". Le manuscrit conclut avec un chapitre de modélisation de la cinétique de libération à partir des systèmes employés. Etant données les applications potentielles de tels hydrogels sous forme de films pour traiter les affections de la peau, les résultats préliminaires de libération de lévofloxacine à partir d'un système transdermique qui simule les dermes humains sont montrés. / The main objective of the PhD thesis entitled “Complex polymeric biomaterials for modeling the drug release kinetics” was to bring contributions in modeling the release kinetics of active ingredients from polymer-drug systems, attempting to reduce the "burst effect"' and increase the release time. The basic idea of the thesis was, in a first stage, the encapsulation of the drug in liposomes -lipid vesicles capable of drug transport- and their subsequent inclusion in polymeric hydrogels in the rationale of creating two "barriers" in drug release process. First, obtained hydrogels are based on chitosan/gelatin and chitosan/poly(vinyl alcohol) partly covalently crosslinked with glutaraldehyde and dominantly ionically with anion sulfate or tripolyphosphate. A second category is based on chitosan hydrogels, alone or in combination with poly(vinyl alcohol), crosslinked with tannic acid through numerous hydrogen bonds. Hydrogels were characterized structurally, morphologically, in terms of the behavior in aqueous media and thermal stability, the qualities of biomaterial (hemocompatibility and cytotoxicity), the ability to include and release a model compound (calcein) free or encapsulated in liposomes. Dependence of properties (swelling, release of soluble compounds included) on the preparation process parameters (amount of crosslinker, polymers ratio used, chitosan molecular weight) is established. Performing calcein release kinetic studies (calcein included directly in hydrogels or encapsulated in liposomes subsequently dispersed in hydrogels) proves the correctness of the starting hypothesis: whatever type of crosslinking applied for the preparation of hydrogels, the release of calcein from complex systems (hydrogel-liposomes-calcein) is much delayed without manifesting practically "burst effect". The paper concludes with a chapter with modeling the release kinetics from the studied systems and with the Conclusions and Perspectives. Given the potential application of such hydrogels in the form of films for treating skin conditions, preliminary results of levofloxacin release from a transdermal system that simulates human dermis are shown.

Ce travail porte sur les propriétés des nanocristaux de cellulose, leur modification de surface et le développement de matériaux avancés. Diverses approches sont utilisées sur ces substrats nanométriques visant à modifier leurs propriétés de surface et étendre leur utilisation dans des applications très sophistiquées, telles que la postsulfation et la désulfatation, le greffage et l'adsorption de polymères, l’oxydation sélective, le greffage moléculaire et l'inclusion "hôte-invité". Sur la base de modifications de surface, l'analyse des propriétés (pour différents taux de groupements sulfates) et divers nanomatériaux dérivés des nanocristaux de cellulose sont étudiés et préparés, notamment des nanocristaux sulfatés à différents taux, des nanocomposites extrudés, des éponges biocomposites et des hydrogels supramoléculaires. L'effet d’un gradient de groupements sulfates sur la chimie de surface, la morphologie et les propriétés physiques des nanocristaux de cellulose est discuté et notamment quatre modèles de section transversale sont comparés pour la détermination de la mesure du degré de substitution surfacique des nanocristaux de cellulose. Une stratégie nouvelle de protection impliquant une double couche polymère et la compatibilisation physique et/ou chimique des nanocristaux de cellulose est proposée afin de promouvoir à la fois la stabilité thermique des nanoparticules et la compatibilité des nanocristaux avec des matrices polymères non polaires au cours de la mise en forme par extrusion. En participant àla réticulation pour la construction de matériaux avancés, des nanocristaux de cellulose sélectivement oxydés (et de la cellulose microfibrillée oxydée pour comparaison) sont introduits dans de l'alginate pour développer des éponges biocomposites présentant une meilleure stabilité mécanique et une meilleure stabilité structurelle. Grâce à la conception intelligente par inclusion 'hôte-invité' in situ entre des nanocristaux de cellulose chimiquement modifiés et la cyclodextrine,deux polysaccharides hydrophiles sont combinés dans des hydrogels supramoléculaires pour l'administration de médicaments. En un mot, cette thèse contribue à l’avancée des nanocristaux de cellulose dans les domaines de l'analyse des propriétés et le développement des applications. / The present work focuses on the properties of cellulose nanocrystals, their surface modification and development of advanced materials. Diverse approaches are employed on these nanoscaled substrates aiming to modify their surface properties and extend their use in highly sophisticated applications, such as postsulfation and desulfation, polymer grafting and adsorption, selective oxidation, molecular grafting, and ‘host-guest' inclusion. On the basis of surface modifications, properties analysis (for different sulfate group contents) and various nanomaterials derived from cellulose nanocrystals are investigated and prepared, including gradient sulfated nanocrystals, extruded nanocomposites, biocomposite sponges, and supramolecular hydrogels. The effect of gradient degrees of sulfate groups on cellulose nanocrystals to surface chemistry, morphology and physical properties are discussed, particularly four cross-section models are compared for the determination of the surface degree of substitution on cellulose nanocrystals. A novel strategy involving a double-polymer-layer shield and physical and/or chemical compatibilization of cellulose nanocrystals is proposed, in order to realize both improvement of thermal stability and promotion of compatibility for nanocrystals with non-polar polymeric matrices during processing by melt-extrusion. With the idea of participating as crosslinking aid for the construction of advanced materials, selectively oxidized cellulose nanocrystals (with oxidized microfibrillated cellulose as comparison) are introduced in alginate for the development of biocomposite sponges with improved mechanical stability or structural stability. Through the smart design of in situ ‘host−guest' inclusion between chemically modified cellulose nanocrystals and cyclodextrin, two hydrophilic polysaccharides are combined in supramolecular hydrogels for use as drug delivery. In a word, this dissertation contributes to the advances of cellulose nanocrystals in the topics of property analysis and application development.

Le fascinant processus par lequel les signaux mécaniques sont transformés en réactions biochimiques dans la nature est appelé mécano-transduction. Le but de ma thèse a été de mimer la Nature en élaborant de nouveaux systèmes enzymatiques mécano-transductifs, i.e des matériaux capables de moduler une catalyse enzymatique lorsqu’ils sont sollicités mécaniquement. Nous avons d’abord étudié l’effet de l’étirement sur les chaînes constitutives de films multicouches de polyélectrolytes, matrices souvent utilisées pour le développement de biomatériaux intelligents. Dans le cadre d’une nouvelle stratégie axée sur la modulation mécanique de la conformation, nous avons ensuite élaboré des matrices étirables à base de poly(éthylène glycol)s. Nous avons en particulier développé de tout nouveaux revêtements covalents appelés nanogels qui se sont avérés être déposables sur le silicone étirable et fonctionnalisables avec différentes biomacromolécules, ouvrant ainsi de nouvelles routes biomimétiques. / The fascinating process by which mechanical signals are transformed into biochemical reactions in Nature is called mechanotransduction. The goal of my PhD was to mimic Nature by elaborating new types of mechanocatalytic materials, i.e materials able to modulate a catalytic activity when mechanically stimulated. We first aimed at understanding the impact of stretching on the structural properties of polyelectrolyte multilayers films, polymeric matrices often used for the design of smart biomaterials. Within the framework of a new strategy essentially relying on mechanically induced conformational changes, we then developed stretchable polymeric matrices based on poly(ethylene glycol)s. We more particularly designed new types of covalent coatings, called nanogels. We showed that these architectures were buildable on stretchable silicone and that they could be functionalized with different types of biomacromolecules; thus opening new biomimetic routes.

Ce travail a eu pour objectif la mise au point d'un nouveau procédé de filage par voie humide dans des conditions de coagulation interrompue pour la formation des fibres creuses mono- et multi-membranaire à base d’hydrogels de chitosane. Pour cela, l’étude du rôle des paramètres de filage (vitesse d’extrusion et d’étirage) et des paramètres physico-chimiques de coagulation (concentration du collodion, nature et concentration de l’agent coagulant) a d'abord permis d’élaborer des fibres creuses à partir d’un macrofilament liquide. Cette approche a été généralisée pour la fabrication de fibres creuses multi-membranaires en mettant au point un procédé de neutralisation à plusieurs étapes au moyen de bains successifs coagulation/lavage conduisant ainsi à la formation d’un assemblage de membranes et d’espaces membranaires. En modifiant la viscosité du collodion et la nature et concentration de la base neutralisante, la microstructure des hydrogels de chitosane a été analysée par diffusion/diffraction de rayonnement (X et lumière) et microscopie électronique. Selon les conditions de coagulation, il est possible de former des hydrogels par assemblages d'agrégats ou encore des structures bien organisées comme les gels de chitosane avec micro-canaux. En résumé, ce travail a permis d’apporter de nouveaux éléments sur le phénomène de coagulation du chitosane pour la formation d’une large gamme de matériaux bio-inspirés "leurres des milieux biologiques" à propriétés biologiques contrôlées pour l'ingénierie tissulaire: tube creux ou multi-membranaires comme substituts vasculaires, ou comme guides pour régénération nerveuse / The main objective of this work was to develop an interrupted wet-spinning process for the elaboration of hollow and multi-membrane chitosane fibers. The knowledge of the specific role of the processing parameters (extrusion rate and coagulation time) and physico-chemical parameters of coagulation (chitosane dope concentration, nature and concentration of the coagulant agent) allow us to elaborate hollow fibers from a liquid macrofiber of chitosane by interrupting the coagulation step through water washing. This approach was generalized for the elaboration of multi-membrane hollow fibers by alternating coagulation baths and water washing baths in a sequenced coagulation process. By modifying the dope viscosity and the nature and concentration of the coagulant agent, the microstructure of chitosan hydrogels was studied by specific scattering and microscopy techniques. Depending on the coagulation conditions, it was possible to process hydrogels with different microstructure consisting of aggregates assembled into micrometric clusters or capillary gels with more organized structures of periodic parallel micro-channels. This work opens the way to elaboration of a wide range of chitosan physical hydrogels based on the concept of “decoy of biological media” with tuneable biological properties for tissue engineering: hollow tubes and multi-membrane tubes as blood vessel substitutes or nerve guides

Ce travail concerne le développement de nouvelles méthodes de filage du chitosane ainsi que l’étude des propriétés morphologiques, mécaniques et biologiques des fibres obtenues, en vue de leur utilisation sous forme de fils et textiles dans des applications biomédicales (en particulier, la constitution de prothèses pariétales pour la chirurgie viscérale et de pansements pour le traitement des plaies chroniques). Les monofilaments sont élaborés à partir de solutions hydroalcooliques de chitosane. Les deux procédés décrits sont basés sur la gélification physique du polymère sans utiliser d’agent réticulant externe. L’étude systématique des paramètres physico-chimiques mis en jeu au cours de la formation des fibres a permis de déterminer les paramètres clés permettant le contrôle de la morphologie cristalline des fibres, notamment les fractions cristalline anhydre et hydratée. Les propriétés mécaniques des fibres de chitosane sont stables au moins jusqu'à 6 mois de stockage à l'ambiante, et ont pu être optimisées en jouant à la fois sur des paramètres « procédé » (étirages du filament aux différentes étapes du procédé d’élaboration) et sur des paramètres physicochimiques (concentration en chitosane dans le collodion, masse moléculaire du polymère et composition du solvant hydroalcoolique). L’observation de la morphologie des fibres à différentes échelles par diffusion/diffraction des rayons X et microscopie électronique en relation avec les propriétés mécaniques a permis d’appréhender l'évolution microstructurale au cours de l'étirage, notamment le mécanisme de formation de fibrilles d'une part, et les échelles clés pour l'interprétation du comportement à rupture des fibres (morphologie en agrégats de 100-300 nm). Enfin, une implantation en souscutané chez le rat de fibres de chitosane possédant différentes morphologies cristallines (anhydre et hydratée) a validé le potentiel de ces fibres pour leurs applications biologiques avec une excellente tolérance des biomatériaux implantés (réponses inflammatoire et tissulaire très limitées) et une faible biodégradabilité après 90 jours d'implantation / This work deals with the development of new chitosan fiber spinning processes and the study of morphological, mechanical and biological properties of obtained fibers, in the perspective of their use as yarns or textiles in biomedical applications (in particular, the design of abdominal reinforcement meshes for visceral surgery and wound dressings for the treatment of chronic wounds). The monofilaments were elaborated from hydroalcoholic chitosan solutions. The two processes that we described are based on the physical gelation of the polymer without using any external crosslinking agent. The systematic study of physico-chemical parameters occurring during the fiber formation allowed to determine the key parameters controlling the crystalline morphology of fibers, especially the anhydrous and hydrated crystalline fractions. The mechanical properties of chitosan fibers are stable at least up to 6 months of storage at ambient atmosphere, and were optimized by acting on processing parameters (filament stretching at different steps of its elaboration) and physico-chemical parameters (chitosan concentration in the dope, molecular weight of the polymer and composition of the hydroalcoholic solvent). The observation of the fiber morphology at different length scales by X-ray diffusion/diffraction and electronic microscopy in relation to their mechanical properties allowed us to comprehend the microstructural evolution during fiber stretching, including the mechanism of fibril formation and the key length scales to understand the behaviour at break of fibers (100-300 nm aggregate morphology). Finally, a subcutaneous implantation of chitosan fibers with different crystalline morphologies (anhydrous and hydrated) validated the potential of these fibers in their biological applications with an excellent tolerance of implanted biomaterials (very low inflammatory and tissue reactions) and a low biodegradability after 90 days of implantation

No description available.

Space-resolved stimulation of active hydrogel layers can be achieved for example by using a micro-heater array. In the current work, we present the interaction of (i) such a rigid array of heating elements that can be selectively activated and (ii) an active thermo-responsive hydrogel layer that responds to the local stimulus change. Due to the respective local actuation, (iii) the surface form of a passive top-layer can be manipulated. We present continuum-based simulative predictions based on the Temperature Expansion Model and compare them to experimental outcomes for the system.

No description available.

Blood vessels including the arteries, veins, and capillaries are a critical and indispensable component of various organisms. Some studies estimate that if all the blood vessels present in our body are arranged in line, they would amount to a total length of approximately 60,000 miles. This distance is enough to circle the world two and a half times! In addition to being all pervasive, blood vessels perform certain key functions such as delivery of oxygen and nutrients to various tissues in the body. They also assist in the spread of diseases such as cancer. Therefore, it is important to study vessels from the point of view of tissue engineering applications. In this study, I have adapted the design of an open-source 3D printed device to create channels in Poly (ethylene glycol) Maleimide (PEG-Mal) hydrogels using the subtractive technique. The PEG-Mal hydrogels can be formed in various formulations to mimic the biophysical and biochemical properties of various tissues such as bone marrow, brain, and lung. These channels created within hydrogels can be easily perfused with physiologically relevant flow rates found in blood vessels and capillaries. Additionally, I have also optimized the hydrogel formulations to improve channel reproducibility. It was found that the number of arms of PEG-Mal contributed the most to channel reproducibility with higher success rates of channel formation in 8-arm gels when compared to 4-arm gels. Therefore, this project delineates the formation of simple in vitro channels in hydrogels which combines properties of the tissue specific extracellular matrix with hemodynamics. It is expected that such a system will find potential use in various tissue engineering and disease modeling studies.