A novel injectable hydrogel system for cell delivery in craniofacial bone tissue engineering was developed in this work. The hydrogel employs a dual solidification mechanism by containing units that gel upon temperature increase to physiological temperature and groups that allow for covalent crosslinking. The successful synthesis of macromers for hydrogel fabrication was demonstrated and structure-property relations were established. The hydrophilic-hydrophobic balance of the macromers was found to be an important design criterion towards their resulting thermal gelation properties. When tested with cells in vitro , macromers with different molecular compositions, molecular weights and transition temperatures were all found to be cytocompatible. The introduction of a chemically crosslinkable group in the macromers resulted in hydrogels with improved stability. The effect of the addition of these highly reactive groups on cell viability was evaluated and parameters that enable viable cell encapsulation in the hydrogels were determined. It was shown that there was a dose- and time-dependent effect of the macromers on cell viability. Increased degrees of modification were found to decrease the thermal transition temperature as well as the cytocompatibility of the macromers. Hydrogels were fabricated at physiological temperature upon physical gelation and chemical crosslinking with the addition of a thermal free radical initiator system. The swelling behavior of the hydrogels was characterized and it was found to be controlled by the chemistry of the macromer end group, the concentration of the initiator system used, the fabrication interval as well as the incubation temperature and medium. In order to evaluate the hydrogels as cell carriers, mesenchymal stems cells were encapsulated in the hydrogels over a 21-day period. Cells retained their viability over the duration of the study and exhibited markers of osteogenic differentiation when cultured with appropriate supplements. These findings hold promise for the use of these hydrogel systems for cell encapsulation in tissue engineering applications.

This study was aimed at designing a cell carrier from an intelligent polymer to achieve loading of mechanical stress for the purpose of improving the tissue engineering capability in vitro. Ethyleneglycoldimethacrylate (EGDMA) crosslinked poly(Nisopropylacrylamide) (pNIPAM) films were prepared by radical polymerization with ultraviolet light (UV) in the presence of photoinitiator 2,2&#039 / -azoisobutyronitrile (AIBN) in isopropanol/water (1:1). Patterns were formed on the surface of the polymers by using silicon wafers with microridges (2 &amp / #956 / m) and grooves (10 &amp / #956 / m) that were prepared by photolithography technique as the template. The surfaces of the films were also modified by adsorption of ELP-RGD6 polypeptide. Bone marrow stem cells (BMSCs) isolated from 6 week old Sprague-Dawley rats were seeded onto the pNIPAM films with different surface topography and chemistry and cultured under static and dynamic conditions. Dynamic conditions were generated by cyclic temperature changes (15 min at 29&deg / C, 30 min at 37&deg / C) for 10 times a day during 5 days starting on the second day post-cell seeding. ELP-RGD6 on the films enhanced initial cell attachment but had no effect on proliferation in long term culturing. However, for the dynamic culturing, ELP was crucial for both retaining cells attached on the surface when the surface became hydrophilic and resulted in weakened cell attachment, and for better communication between cell and material which enhanced the ability of pNIPAM films to transfer mechanical stress on the cells. Dynamic conditions improved cell proliferation but decreased differentiation. Presence of the patterns also influenced the differentiation but did not affected proliferation.

Diese Arbeit befasst sich mit der Synthese und der Charakterisierung von thermoresponsiven Polymeren und ihrer Immobilisierung auf festen Oberflächen als nanoskalige dünne Schichten. Dabei wurden thermoresponsive Polymere vom Typ der unteren kritischen Entmischungstemperatur (engl.: lower critical solution temperature, LCST) verwendet. Sie sind bei niedrigeren Temperaturen im Lösungsmittel gut und nach Erwärmen oberhalb einer bestimmten kritischen Temperatur nicht mehr löslich; d. h. sie weisen bei einer bestimmten Temperatur einen Phasenübergang auf. Als Basismaterial wurden verschiedene thermoresponsive und biokompatible Polymere basierend auf Diethylenglykolmethylethermethacrylat (MEO2MA) und Oligo(ethylenglykol)methylethermethacrylat (OEGMA475, Mn = 475 g/ mol) über frei radikalische Copolymerisation synthetisiert. Der thermoresponsive Phasenübergang der Copolymere wurde in wässriger Lösung und in gequollenen vernetzten dünnen Schichten beobachtet. Außerdem wurde untersucht, inwiefern eine selektive Proteinbindung an geeignete funktionalisierte Copolymere die Phasenübergangstemperatur beeinflusst. Die thermoresponsiven Copolymere wurden über photovernetzbare Gruppen auf festen Oberflächen immobilisiert. Die nötigen lichtempfindlichen Vernetzereinheiten wurden mittels des polymerisierbaren Benzophenonderivates 2 (4 Benzoylphenoxy)ethylmethacrylat (BPEM) in das Copolymer integriert. Dünne Filme der Copolymere mit ca. 100 nm Schichtdicke wurden über Rotationsbeschichtung auf Siliziumwafer aufgeschleudert und anschließend durch Bestrahlung mit UV Licht vernetzt und auf der Oberfläche immobilisiert. Die Filme sind stabiler je größer der Vernetzeranteil und je größer die Molmasse der Copolymere ist. Bei einem Waschprozess nach der Vernetzung wird beispielsweise aus einem Film mit moderater Molmasse und geringem Vernetzeranteil mehr unvernetztes Copolymer ausgewaschen als bei einem höhermolekularen Copolymer mit hohem Vernetzeranteil. Die Quellbarkeit der Polymerschichten wurde mit Ellipsometrie untersucht. Sie ist größer je geringer der Vernetzeranteil in den Copolymeren ist. Schichten aus thermoresponsiven OEG Copolymeren zeigen einen Volumenphasenübergang vom Typ der LCST. Der thermoresponsive Kollaps der Schichten ist komplett reversibel, die Kollapstemperatur kann über die Zusammensetzung der Copolymere eingestellt werden. Für einen Vergleich dieser Eigenschaften mit dem gut charakterisierten und derzeit wohl am häufigsten untersuchten thermoresponsiven Polymer Poly(N-isopropylacrylamid) (PNIPAM) wurden zusätzlich photovernetzte Schichten aus PNIPAM hergestellt und ebenfalls ellipsometrisch vermessen. Im Vergleich zu PNIPAM verläuft der Phasenübergang der Schichten aus den Copolymeren mit Oligo(ethylenglykol)-seitenketten (OEG Copolymere) über einen größeren Temperaturbereich. Mit Licht einer Wellenlänge > 300 nm wurden die photosensitiven Benzophenongruppen selektiv angeregt. Bei der Verwendung kleinerer Wellenlängen vernetzten die Copolymerschichten auch ohne die Anwesenheit der lichtempfindlichen Benzophenongruppen. Dieser Effekt ließ sich zur kontrollierten Immobilisierung und Vernetzung der OEG Copolymere einsetzen. Als weitere Methode zur Immobilisierung der Copolymere wurde die Anbindung über Amidbindungen untersucht. Dazu wurden OEG Copolymere mit dem carboxylgruppenhaltigen 2 Succinyloxyethylmethacrylat (MES) auf mit 3 Aminopropyldimethylethoxysilan (APDMSi) silanisierte Siliziumwafer rotationsbeschichtet, und mit dem oligomeren α, ω Diamin Jeffamin® ED 900 vernetzt. Die Vernetzungsreaktion erfolgte ohne weitere Zusätze durch Erhitzen der Proben. Die Hydrogelschichten waren anschließend stabil und zeigten neben thermoresponsivem auch pH responsives Verhalten. Um zu untersuchen, ob die Phasenübergangstemperatur durch eine Proteinbindung beeinflusst werden kann, wurde ein polymerisierbares Biotinderivat 2 Biotinyl-aminoethylmethacrylat (BAEMA) in das thermoresponsive Copolymer eingebaut. Der Einfluss des biotinbindenen Proteins Avidin auf das thermoresponsive Verhalten des Copolymers in Lösung wurde untersucht. Die spezifische Bindung von Avidin an das biotinylierte Copolymer verschob die Übergangstemperatur deutlich zu höheren Temperaturen. Kontrollversuche zeigten, dass dieses Verhalten auf eine selektive Proteinbindung zurückzuführen ist. Thermoresponsive OEG Copolymere mit photovernetzbaren Gruppen aus BPEM und Biotingruppen aus BAEMA wurden über Rotationsbeschichtung auf Gold- und auf Siliziumoberflächen aufgetragen und durch UV Strahlung vernetzt. Die spezifische Bindung von Avidin an die Copolymerschicht wurde mit Oberflächenplasmonenresonanz und Ellipsometrie untersucht. Die Bindungskapazität der Schichten war umso größer, je kleiner der Vernetzeranteil, d. h. je größer die Maschenweite des Netzwerkes war. Die Quellbarkeit der Schichten wurde durch die Avidinbindung erhöht. Bei hochgequollenen Systemen verursachte eine Mehrfachbindung des tetravalenten Avidins allerdings eine zusätzliche Quervernetzung des Polymernetzwerkes. Dieser Effekt wirkt der erhöhten Quellbarkeit durch die Avidinbindung entgegen und lässt die Polymernetzwerke schrumpfen. / This work describes the synthesis and characterization of thermoresponsive polymers and their immobilisation on solid substrates as nanoscale thin films. The used polymers were of the lower critical solution temperature (LCST) type. They are well soluble in a solvent below a and get insoluble above a certain temperature, thus they exhibit a phase transition at a critical temperature. Different thermoresponsive biocompatible copolymers based on oligo(ethylene glycol) methyl ether methacrylate (OEGMA475) and di(ethylene glycol) methyl ether methacrylate (MEO2MA) were synthesized by free radical polymerization. The phase transition was observed in solution and in thin immobilized copolymer layers. Further regarding the phase transition the influence of selective protein binding onto functionalized copolymers was studied. Solid surfaces were modified with thermoresponsive copolymers based on MEO2MA, OEGMA475 and 2 (4 benzoylphenoxy)ethyl methacrylate (BPEM) as photo crosslinkable groups. Thin films of 100 nm thickness were spin-casted onto silicon wafers and subsequently crosslinked and immobilized by irradiation with UV-light. Their stability is controlled by the crosslinker ratio and by the molar mass of the copolymers. For instance a washing process after crosslinking removes more unbound polymer if the polymer contains less crosslinker and has a lower molecular weight. The swellability of the films was investigated by ellipsometry. It gets higher with lower crosslinker ratio. Layers of thermoresponsive copolymers exhibited a swelling/ deswelling phase transition of the lower critical solution temperature (LCST) type. The transition is completely reversible and the transition temperature can be adjusted by the composition of the copolymers. Compared to similarly synthesized photo-crosslinked layers of the well investigated thermoresponsive copolymer poly-(N-isopropyl acrylamide) (PNIPAM) the phase transition exceeds a larger temperature range. The photo-crosslinking of the OEG copolymers was accomplished in a controlled manner with light of wavelengths > 300 nm. Light of smaller wavelengths crosslinked the copolymer layers even without the presence of photosensitive groups. This effect could be exploited for a controlled immobilization and crosslinking of the OEG copolymers. As further method for crosslinking the formation of amide bonds was investigated. Therefore OEG copolymers containing 2 succinyloxyethyl methacrylate (MES) were spin-casted onto silicon substrates silanized with (3 aminopropyl)dimethylethoxysilane (APDMSi) and crosslinked with oligomeric α, ω diamine Jeffamin® ED 900. The crosslinking reaction was carried out by annealing the dry substrate. No further additives were added for the reaction. After annealing the hydrogel layers were stable against washing and showed thermoresponsive and pH responsive behaviour. In order to investigate whether the phase transition can be affected by specific protein binding, a polymerizable biotin derivative biotinyl-2-aminoethyl methacrylate (BAEMA) was integrated into the base thermoresponsive OEG copolymer. The influence of avidin on its thermoresponsive behaviour was investigated. The specific binding of avidin to the bioitinylated copolymer caused a marked shift of the transition temperature to higher temperatures. Control experiments proved that this effect can be ascribed to a specific protein binding. Thermoresponsive OEG Copolymers with photo-crosslinkable groups from BPEM and biotin groups from BAEMA were spin casted onto gold and silicon substrates and subsequently crosslinked by irradiation with UV light. The specific binding of Avidin onto the copolymer layer was investigated by surface plasmon resonance spectroscopy and ellipsometry. The binding capacity was higher if the mesh size of the hydrogel layers was higher. Upon binding of the Avidin the swellability of the layers was increased. At temperatures below the phase transition for loosely crosslinked copolymer layers an additional crosslinking effect of Avidin was observed. This effect counteracts the swelling of the hydrogel and leads to a shrinkage of the hydrogel layer.

<p>Traditional small molecule chemotherapeutics show limited effectiveness in the clinic as their poor pharmacokinetics lead to rapid clearance from circulation and their exposure to off-target tissues results in dose-limiting toxicity. The objective of this dissertation is to exploit a class of recombinant chimeric polypeptides (CPs) to actively target drugs to tumors as conjugation to macromolecular carriers has demonstrated improved efficacy by increasing plasma retention time, reducing uptake by healthy tissues, and enhancing tumor accumulation by exploiting the leaky vasculature and impaired lymphatic drainage characteristic of solid tumors. CPs consist of two principal components: (1) a thermally responsive elastin-like polypeptide (ELP) that displays a soluble-to-aggregate phase transition above a characteristic transition temperature (Tt); and (2) a cysteine-rich peptide fused to one end of the ELP to which small molecule therapeutics can be covalently attached (the conjugation domain). This work describes the development of CP drug-loaded nanoparticles that can be targeted to solid tumors by the external application of mild regional hyperthermia (39-43°C). </p><p>Highly repetitive ELP polymers were assembled by Plasmid Reconstruction Recursive Directional Ligation (PRe-RDL), in which two halves of a parent plasmid, each containing a copy of an oligomer, were ligated together to dimerize the oligomer and reconstitute the functional plasmid. Chimeric polypeptides were constructed by fusing the ELP sequence to a (CGG)8 conjugation domain, expressed in Escherichia coli, and loaded with small molecule hydrophobes through site specific attachment to the conjugation domain. Drug attachment induced the assembly of nanoparticles that retained the thermal responsiveness of the parent ELP in that they experienced a phase transition from soluble nanoparticles to an aggregated phase above their Tt. Importantly, the Tt of these nanoparticles was near-independent of the CP concentration and the structure of the conjugated molecule as long as it displayed an octanol-water distribution coefficient (LogD) > 1.5. </p><p>A series of CP nanoparticles with varying ratios of alanine and valine in the guest residue position was used to develop a quantitative model that described the CP transition temperature in terms of three variables - sequence, chain length, and concentration - and the model was used to identify CPs of varying molecular weights that displayed transition temperatures between 39°C and 43°C. A murine dorsal skin fold window chamber model using a human tumor xenograft was used to validate that only the thermoresponsive CP nanoparticles (and not the controls) exhibited a micelle-to-aggregate phase transition between 39-43°C in vivo. Furthermore, quantitative analysis of the biodistribution profile demonstrated that accumulation of these thermoresponsive CP nanoparticles was significantly enhanced by applying heat in a cyclical manner. It is hoped that this work will provide a helpful resource for the use of thermoresponsive CP nanoparticles in a variety of biomedical applications.</p> / Dissertation

Increasing demands for organ transplants and the depleting supply of available organs has heightened the need for alternatives to this growing problem. Tissue engineers strive to regenerate organs in the future; however doing so requires a fundamental understanding of organ development and its key processes. The first chapter of this thesis provides a brief overview of developmentally inspired engineering, specifically in the context of how I approach this challenge in this thesis. The second chapter provides an in depth review of current and past work focused on organ regeneration from a developmentally-inspired perspective, and using tooth formation as a model system. The third chapter describes the design and fabrication of a thermoresponsive polymer inspired by an embryonic induction mechanism, and demonstrates its ability to induce tooth differentiation in vitro and in vivo. This is effectively a 3D `shrink wrap'-like polymer sponge that constricts when it is warmed to body temperature and induces compaction of cells contained within it, hence recapitulating the mesenchymal condensation process that has been shown to be a key induction mechanism that triggers formation of various epithelial organs, including tooth in the embryo. The fourth chapter describes the fabrication of a novel microarray screening platform consisting of a unique set of ECM proteins (collagen VI, tenascin, and combination of the two at different coating densities) on an array of soft substrates (~130-1500 Pa) that are physiologically relevant to the embryonic microenvironment. This technology demonstrated the capacity to analyze combinatorial effects of these ECM proteins and soft substrates on cell density, cell area and odontogenic differentiation in murine mandible embryonic mesenchymal cells. The fifth chapter of this thesis summarizes and discusses the advantages, limitations and future potential of the findings described in the previous two chapters in the context of organ engineering and regeneration. Taken together, the work and results presented in this thesis have led to the development of new insights, approaches and tools for studying organ formation and potentially inducing organ regeneration, which are inspired by key developmental mechanisms used during embryonic organ formation. / Engineering and Applied Sciences

Les réactions de Diels-Alder (DA) sont connues pour leur thermo-réversibilité. A basse température, le diène et les fonctions réactives diénophiles réagissent ensemble par la réaction de (DA) pour donner l’adduit. Le but de notre thèse est d’élaborer des réseaux réticulés thermoréversibles à base époxy-amine en utilisant des réactions de Diels-Alder. La thèse est composée de cinq chapitres dont le premier est consacré à la partie bibliographique. Celle-ci résume une partie des travaux réalisés sur la synthèse d'adduits et expose les différentes conditions utilisées pour aboutir à la synthèse, ainsi que les différentes méthodes d’analyse pour la caractérisation de ces adduits. Le deuxième chapitre est consacré à la synthèse et caractérisations des pré-polymères multi-diéne furanne ester. La synthèse de ces pré-polymères a été réalisée et confirmée par la RMN-1H, avec l’apparition de nouveaux signaux entre 4 et 5 ppm prouvant l’estérification. L’analyse IR- TF confirme l’apparition des deux bandes de vibration correspondantes à la fonction ester. Le troisième chapitre est consacré à la synthèse et caractérisations des pré-polymères acides multi-diénophiles (diénophiles ouverts) et une tri-maléimide diénophile (diénophile fermé). Les analyses RMN-1H et IR-TF confirment, respectivement, la disparition des protons de la fonction amine et les deux bandes anhydride, avec ouverture de la fonction époxy. Le quatrième chapitre est consacré à la synthèse et caractérisations de pré-polymères multi-diène furane. Ceux-ci ont été réalisés par la réaction de copolymérisation entre les fonctions époxydes de la DGEBA et la phényl diglycidyl éther (PGE) avec la furfurylamine (FAM). La RMN-1H a permis de calculer la fonctionnalité en fonction furane des diènes et de déterminer leur masse molaire moyenne en nombre. L’analyse thermogravimétrie (ATG) et l’analyse thermique par DSC ont montré que ces diènes sont des composés amorphes présentant une Tg de l’ordre de 20°C et restent stables thermiquement jusqu'à une température de 230°C. Enfin, dans le cinquième et dernier chapitre, la synthèse de réseaux thermoréversibles formés par la réaction de Diels-Alder entre les pré-polymères diène et la tri-maléimide diénophile sera présentée. La thermoréversibilité, les propriétés thermiques et d’autoréparation des réseaux seront étudiées / The Diels-Alder (DA) reactions are known for their thermo-reversibility. At low temperatures, the diene and dienophile reactive functional groups react together by the reaction of (DA) to give the adduct. The aim of this thesis is to develop the thermo crosslinked networks based epoxy-amine using Diels-Alder reaction. The thesis consists of five chapters; the first is devoted to the bibliographic part. It summarizes some of the work on the synthesis of adducts and describes various conditions used to achieve the synthesis, and the different methods of analysis for the characterization of these adducts. The second chapter is devoted to the synthesis and characterization of multi-diene pre-polymers furan ester. The synthesis of these pre-polymers was carried out and confirmed by 1H-NMR, with the appearance of new signals between 4 and 5 ppm proving the esterification. FT-IR analysis confirmed the appearance of two bands corresponding to the ester vibration bands. The third chapter is devoted to the synthesis and characterization of pre-polymers multi-dienophiles acids (open dienophiles) and a tri-maleimide dienophile (dienophile closed). 1H-NMR analysis and FT-IR confirm respectively, the disappearance of the amine protons and two anhydride bands, with opening of the epoxy function. The fourth chapter is devoted to the synthesis and characterization of pre-polymers multi-furan diene. These were synthesized by the copolymerization reaction between the epoxy functions of DGEBA and diglycidyl phenyl ether (PGE) with furfurylamine (FAM). 1H-NMR was used to calculate the functionality dienes and to determine their number-average molar mass. The thermo gravimetric analysis (TGA) and the thermal analysis by DSC showed that these dienes are amorphous compounds having a Tg about 20°C and are thermally stable up to a temperature of 230°C. In the fifth and final chapter, the synthesis of thermo-reversible networks formed by the Diels-Alder reaction between pre-polymers diene and tri-maleimide dienophile will be presented. The thermoreversibility, thermal properties and self-healing networks are studied

This thesis investigated a new group of poly(Bd)/poly(Bd-co-MAA) core-shell particles that were ionically crosslinked and cast as nanostructured ionomer films from aqueous dispersions. The new group of poly(Bd)/poly(Bd-co-MAA) core-shell particles were studied for structure-property relationships and morphology. The covalent crosslinking content in the core and the shell were varied at constant ionic crosslinking. Stress-strain data showed control of the nanostructured films. The chain transfer agent used during the preparation of the nanoparticles core-shells was shown to independently tune the mechanical properties of the films.

Cette thèse s’articule autour de systèmes innovants de délivrance d’anticancéreux pour répondre aux limitations actuelles des systèmes de type nanoparticules. Celles-ci permettent l’encapsulation d’anticancéreux pour prolonger leur temps de circulation dans le sang et diminuer leurs effets secondaires. Néanmoins les produits disponibles en cliniques ne permettent pas un contrôle précis de la libération de la substance active, ni un ciblage de la tumeur.Pour répondre à ces deux limitations, nous avons synthétisé un copolymère thermosensible ayant une température critique haute de solubilité (upper critical solution temperature, UCST) pour formuler des nanoparticules encapsulant physiquement la doxorubicine. Celles-ci permettent la libération contrôlée de la substance active par hyperthermie modérée à 43 °C. Nous avons étudié notre système d’un point de vue physico-chimique et évalué sa cytotoxicité in vitro sur des cellules de cancer de l’ovaire.Nous avons également opté pour une approche via couplage chimique entre une substance active, le paclitaxel, et le polymère afin de permettre l’administration par la voie sous-cutanée d’anticancéreux. En effet, cette voie d’administration est peu utilisée pour les anticancéreux car certains d’entre eux induisent une toxicité locale au site d’injection de type irritation / nécrose de la peau. Nous avons évalué si d’une part, l’approche prodrogue polymère hydrophile permet d’empêcher cette toxicité locale et si d’autre part, l’approche prodrogue polymère UCST permet d’obtenir des nanoparticules stables à température ambiante en vue d’une administration par la voie sous-cutanée. Une fois administrées, les nanoparticules deviennent hydrophiles par le changement de température, 34 °C dans le tissu sous-cutané, et peuvent donc diffuser librement jusqu’à atteindre la circulation sanguine. Nos travaux ont permis d’évaluer l’approche prodrogue polymère hydrophile in vivo chez la souris nude, ainsi que de décrire pour la première fois la synthèse de prodrogues polymères UCST. / This thesis focuses on innovative drug delivery systems of anticancer drugs to tackle the current limitations of formulations based on nanoparticles. These allow encapsulation of anticancer drugs to prolong their circulation time in the blood stream and to decrease side effects. Yet, nanoparticle formulations available in the clinic do not allow a precise control on the drug release nor targeting of the tumor.To overcome these hurdles, we have synthesized a thermoresponsive copolymer exhibiting an upper critical solution temperature (UCST) to formulate nanoparticles physically encapsulating doxorubicin. These allow controlled release of the anticancer drug by mild hyperthermia at 43 °C. We have studied our system from a physico-chemical point of view and evaluated its cytotoxicity in vitro on ovarian cancer cells.We have also tried a chemical coupling approach between the polymer and the anticancer drug, paclitaxel, to allow innocuous subcutaneous administration. In did, this route of administration is seldom used for anticancer drugs as some of them induce local toxicity at the site of injection in the form of skin irritation / necrosis. We assessed if a hydrophilic polymer prodrug approach allows innocuous subcutaneous administration of an irritant drug; and if a UCST polymer prodrug approach enables formation of stable nanoparticles at room temperature for subcutaneous administration. Once in the subcutaneous tissue at 34 °C, they would solubilize and become hydrophilic thus could freely diffuse to reach the blood circulation. We have managed to evaluate the hydrophilic polymer prodrug approach in vivo on nude mice and we are the first to describe the synthesis of UCST polymer prodrug.

A stimuli-responsive microgel is a three-dimensional polymer network that is able to absorb and expel a solvent (commonly water). These materials are unique in the fact that their sponge-like behavior can be actuated by environmental cues, like temperature, ion concentration, pH, and light. Because of the dynamic properties of these materials they have found applications in drug-delivery systems, micro-assays, selective filtration, artificial muscle, and non-fouling surfaces. The most well-known stimuli-responsive polymer is Poly(N-isopropylacrylamide) or PNIPAAm and it experiences a switchable swelling or deswelling over a critical temperature ( Tc=~32°C). Below the critical temperature, the gel begins mixing with the surrounding solvent and swells; above this temperature, the opposite is true. The unconstrained hydrogel will continue to swell in all directions until equilibrium is established between its propensity for mixing with the surrounding solvent and the elastic restoring forces of the gel matrix. The strength of the elastic restoring forces is dependent on the interconnectedness of the polymer network and is therefore a function of crosslink density. An increase in crosslink density results in a decreased swelling and vice versa. If the hydrogel is mechanically constrained to a surface, it can experience various wrinkling and buckling conformations upon swelling, as the stresses associated with its confinement are relieved. These conformation characteristics are a strong function of geometry (aspect ratio) and extent of swelling (i.e. crosslink density). In order to capitalize on the utility of this material, it is imperative that its volume transition is well characterized and understood. Toward this end, pNIPAAm gels have been created with 1x10-7 to 2x10-³ mol/cm³ crosslink density and characterized. This was done by first examining its bulk, unattached swelling ability and then by evaluating its microscale properties as a surfaceconfined monolithe. The latter was achieved through the use of confocal microscopy and copolymerization with a fluorescent monomer. This method allows for a detail analysis of the deformations experienced (bulk-structural bending and surface undulating) and will ultimately lend itself to the correlation between crosslink density and the onset of mechanical phenomena.

Research of new sustainable and low cost materials, such as cellulose, is of high interest. Modifications of the cellulose can be performed in order to create a “smart” material which responds to external stimuli, such as variations in pH and temperature, by changing its properties. This “smart” behavior is observed in some polymers, however, for certain applications they exhibit poor mechanical properties. These polymers can be bound by physical adsorption to cellulose, both in macro and nano scale, creating an improved “smart” composite material. In this project, thermoresponsive block-copolymers with different lengths of poly (diethylene glycol) methacrylate (PDEGMA) and poly N-(2-dimethylamino ethyl) methacrylate (PDMAEMA) in only one length, PDMAEMA-b-PDEGMA, were synthesized employing atom transfer radical polymerization (ATRP). 1H-NMR, SEC and DLS were used to characterize the block-copolymers. UV-Vis spectroscopy was employed to confirm the thermo-responsive behavior of the charged and uncharged block-copolymers, being lower for the higher molecular weight ones due to the higher polymer-polymer interactions. In a second step, PDMAEMA was charged positively by quaternization of its amine group with ICH3. Polyelectrolyte titration was used to determine the total number of charges in the quaternized block-copolymers. In addition, TEMPO-oxidized nanofibrillated cellulose (NFC) was produced by procedures found in literature. Finally, adsorption of the cationic block-copolymers onto the anionic NFC in tris base at pH 8.3 was performed and purified by consecutive filtrations, creating a novel smart composite material with different PDEGMA lengths in the block-copolymer. FT-IR confirmed that the block-copolymers were successfully adsorbed to the NFC. TGA results showed a higher thermal stability for the composite than for the TEMPO-NFC and quaternized block-copolymers. The block-copolymer modified NFC exhibited thermoresponsive behavior with LCST’s ranging from 30 to 44 °C, from higher to lower molecular weights, respectively.  Adsorption of polyelectrolytes in modified cellulose could be a promising way to create smart improved materials in further research.