No description available.

Stimuli-sensitive hydrogels have an outstanding potential for miniaturized, integrated sensor, and actuator systems and especially for lab-on-chip technology, but the application is still in its infancy. One major reason may be that design and realization of hydrogel-based systems are exceptionally complex and demanding. Here, the design parameters of a key component, the hydrogel-based valve, are discussed in their entirety. Key developments in the fields of stimuli-sensitive hydrogels are highlighted and the necessary know-how in material behavior, microstructuring technologies, modeling and name five essential design guidelines as well as scaling laws for hydrogelbased components, including microfluidic one-directional valves, microelectromechanical systems valves, self-regulating, chemomechanical valves, and chemofluidic transistors, is provided.

No description available.

In recent years, there has been a growing interest within the field of soft materials engineering on the development of advanced hydrogel systems with well-defined chemistries and morphologies that can be customized to suit various applications ranging from biomedical to environmental to personal care. In any case, careful selection of the building block materials, crosslinking chemistry, degradation pathway, and overall hydrogel architecture is essential to ensure the final design (and the resulting degradation components if relevant) are safe/non-toxic, mechanically tunable, and overall translatable for their intended end use given industry safety/production standards. In this thesis, the utility of starch nanoparticles created by a reactive extrusion process was explored as one such building block for creating renewable hydrogels. Starch was reactively extruded by EcoSynthetix Inc. to create starch nanoparticles (SNPs) that are attractive as hydrogel building blocks due to their inherent small size (25-50 nm), generally safe degradation products, overall net neutral charge, high deformability/viscoelastic properties, stability in solution without collapsing or changing size (on the order of months), and the ability to be manufactured at a multiple kg/hr rate; in comparison, other manufacturing methods of SNPs suffer from a lack of scalability or require the use of potentially toxic solvents, making them less amenable to biological or environmental/agricultural applications. The amorphous nature of the starch also allows for facile functionalization to further chemically modify and/or crosslink the SNPs through surface functional group (i.e. hydroxyl) modification chemistries. The nanoparticle nature of the SNP building block, coupled with the facile functionalizability of the SNPs, also makes SNPs ideal building blocks for the design and fabrication of nanoparticle network hydrogels (NNHs) in which NPs create an interconnected network on their own on, in addition to, other polymeric networks at any desired length scale. There are a variety of NNH architectures that can be achieved through careful design considerations. More specifically, herein colloidal NNHs were created using UV photopolymerization post-functionalization with methacrylic anhydride, which leaves a vinyl group on the SNP surface. Alternately, plum pudding NNHs were created by mixing aldehyde-functionalized SNPs with amine-bearing O-carboxymethyl chitosan that were able to chemically react via hydrolytically labile imine bonds. The properties of various types of colloidal and plum-pudding hydrogels based on SNPs were tested and subsequently compared through a range of different performance tests such as rheological and micromechanical force testing, swelling/degradation kinetics, their potential for controlled bioactive release, and overall toxicity (cell and organ level). In addition to these macroscopic performance tests, the internal morphologies of both colloidal and plum pudding NNHs were assessed with small angle and very small angle neutron scattering experiments to glean insight into how these internal structures correlate to macroscopic properties. For all experiments, the effect of using SNPs versus typical cold water-soluble branched starch (SS) was assessed to further understand the impact of making hydrogels from nanoscale rather than soluble polymer building blocks, with the small size of SNPs compared to the large hydrodynamic radius of SS consistently allowing for greater control over the range of potential hydrogel properties. The results of these studies suggest that SNP-based NNHs are promising materials for studying the encapsulation and release of small molecules in both in vitro and in vivo settings. For example, the photopolymerization of methacrylated SNP-based NNH coatings can be fabricated at much higher concentrations than possible with conventional starch (35% for SNP, 10% for SS), leading to denser and stiffer gels compared to SS controls albeit with slightly longer gelation times due to the reduced conformational mobility of the polymerizable methacrylate groups on the SNPs. The addition of charge (cationic or anionic) to the SNP surface further increases the bulk gelation time while significantly reducing the observed changes in SNP deformation during photogelation as confirmed via very small angle neutron scattering experiments. Other functional groups were also demonstrated to be introduced to SNPs to enable different types of gelation for different applications. For example, in situ-gelling and degradable bulk nanoparticle network hydrogels consisting of oxidized starch nanoparticles (SNPs) and carboxymethyl chitosan (CMCh) were created for intranasal delivery that could be delivered into the nose via a commercial atomization device to enable high nasal mucosal retention and functional controlled release of the peptide drug PAOPA, a positive allosteric modulator of dopamine D2 receptor. Selected gels shown to alleviate negative behavioural abnormalities associated with for up to 72 hours in pre-clinical rat models of schizophrenia at a low drug dosage (0.5 mg/kg), compared to just a few hours with the drug alone. Finally, the functionalization of SNPs with hydrophobic groups (via grafting the starch with octenyl succinic acid (OSAn) or succinic anhydride (SAn)) was demonstrated as a promising delivery system for agricultural applications. Hydrophobization increased the contact angle of a sprayed watermelon and pumpkin leaves from <60˚ (unmodified) to ~80˚ when modified (DS 0.25), while confocal fluorescence microscopy confirmed that the hydrophobized SNPs can both adhere to the leaf surface as well as penetrate into the leaves when sprayed due to their small size (25-50 nm). Future work will look at other methods of crosslinking SNPs (i.e. Michael addition, hydrazone, and alkyne-azide “click” chemistry, amongst others) to see if there are beneficial differences compared to analogous hydrogels made from macroscopic alternatives (i.e. polymers alone) and to follow-up the findings already gleaned within this thesis. Further information on the impact and potential follow-up experiments for the work conducted in this thesis will be explained in Chapter 6 on final outlooks and conclusions of the following work. / Thesis / Doctor of Philosophy (PhD) / This thesis describes the chemical and physical modification of commercially-available starch nanoparticles (SNPs) to rationally create novel hydrogel systems. These gel-like networks are made by chemically connecting starch nanoparticles (with sizes on the 10-8 m length scale) by introducing various reactive chemical groups onto the surface of SNPs, enabling the creation of hydrogels with well-defined structures, features, and properties. Careful selection of the crosslinking chemistry made it possible to tune hydrogel properties to specific application requirements, such as the targeted delivery of pharmaceuticals (including the intranasal delivery of antipsychotic drugs to the brain, a key technical challenge to improve the quality of life of patients with mental health challenges) and agrochemical agents or as an anti-fouling coating. The hydrogels created herein are attractive since they directly incorporate nanoscale particles generated from a sustainable source and are generally regarded as safe (GRAS) in terms of their degradation products once they break down, a rare trait for nanoparticles of this size. The existing industrial-scale production of the SNPs also enables facile scaling of these strategies for ultimate commercial translation.

The aim of the thesis was to develop water soluble poly(2-oxazoline) (POx) copolymers with new side group functionalities, which can be used for the formation of hydrogels in biomedical applications and for the development of peptide-polymer conjugates. First, random copolymers of the monomer MeOx or EtOx with ButEnOx and EtOx with DecEnOx were synthesized and characterized. The vinyl functionality brought into the copolymer by the monomers ButEnOx and DecEnOx would later serve for post-polymerization functionalization. The synthesized copolymers were further functionalized with thiols via post-polymerization functionalization using a newly developed synthesis protocol or with a protected catechol molecule for hydrogel formation. For the formation of peptide-polymer conjugates, a cyclic thioester, namely thiolactone acrylamide and an azlactone precursor, whose synthesis was newly developed, were attached to the side chain of P(EtOx-co-ButEnOx) copolymers. The application of the functionalized thiol copolymers as hydrogels using thiol-ene chemistry for cross-linking was demonstrated. The swelling behavior and mechanical properties were characterized. The hydrophilicity of the network as well as the cross-linking density strongly influenced the swelling behavior and the mechanical strength of the hydrogels. All hydrogels showed good cell viability results. The hydrogel networks based on MeOx and EtOx were loaded with two dyes, fluorescein and methylene blue. It was observed that the uptake of the more hydrophilic dye fluorescein depended more on the ability of the hydrogel to swell. In contrast, the uptake of the more hydrophobic dye methylene blue was less dependent on the swelling degree, but much more on the hydrophilicity of the network. For the potential application as cartilage glue, (biohybrid) hydrogels were synthesized based on the catechol-functionalized copolymers, with and without additional fibrinogen, using sodium periodate as the oxidizing agent. The system allowed for degradation due to the incorporated ester linkages at the cross-linking points. The swelling behavior as well as the mechanical properties were characterized. As expected, hydrogels with higher degrees of cross-linking showed less swelling and higher elastic modulus. The addition of fibrinogen however increased the elasticity of the network, which can be favorable for the intended application as a cartilage glue. Biological evaluation clearly demonstrated the advantage of degradable ester links in the hydrogel network, where chondrocytes were able to bridge the artificial gap in contrast to hydrogels without any ester motifs. Lastly, different ways to form peptide-polymer conjugates were presented. Peptides were attached with the thiol of the terminal cysteine group to the vinyl side chain of P(EtOx-co-ButEnOx) copolymers by radical thiol-ene chemistry. Another approach was to use a cyclic thioester, thiolactone, or an azlactone functionality to bind a model peptide via native chemical ligation. The two latter named strategies to bind peptides to POx side chains are especially interesting as one and in the case of thiolactone two free thiols are still present at the binding site after the reaction, which can, for example, be used for further thiol-ene cross-linking to form POx hydrogels. In summary, side functional poly(oxazoline) copolymers show great potential for numerous biomedical applications. The various side chain functionalities can be introduced by an appropriate monomer or by post-polymerization functionalization, as demonstrated. By their multi-functionality, hydrogel characteristics, such as cross-linking degree and mechanical strength, can be fine-tuned and adjusted depending on the application in the human body. In addition, the presented chemoselective and orthogonal reaction strategies can be used in the future to synthesize polymer conjugates, which can, for example, be used in drug delivery or in tissue regeneration. / Das Ziel der Arbeit war es, wasserlösliche Poly(2-oxazolin) (POx) Copolymere mit neuen Seitenkettenfunktionalitäten zu entwickeln, welche zur Synthese von Hydrogelen für biomedizinische Anwendungen und zur Entwicklung von Peptid-Polymer Konjugaten genutzt werden können. Zunächst wurden Copolymere aus den Monomeren MeOx oder EtOx mit ButEnOx und EtOx mit DecEnOx synthetisiert und anschließend charakterisiert. Die Monomere wurden statistisch miteinander copolymerisiert, indem sie zusammen zum Start der Reaktion in das Reaktionsgefäß gegeben wurden. Die Vinyl Funktionalität, die durch die Monomere ButEnOx und DecEnOx eingebracht wurde, kann später zur nachträglichen Funktionalisierung am Polymer verwendet werden. Die synthetisierten Copolymere wurden weiterhin mit Thiolen oder mit funktionellen Catecholgruppen ausgestattet, um Hydrogele herzustellen. Um Peptid-Polymer Konjugate zu bilden, wurden zyklische Thioester, genauer Thiolacton acrylamid und ein Azlacton Präkursor, dessen Synthese neu entwickelt wurde, an die Seitenkette von P(EtOx-co-ButEnOx) Copolymere angebunden. Im Folgenden wurde die Anwendung der thiol funktionalisierten Copolymere als Hydrogele, welche mittels radikalischer Thiol-ene Chemie vernetzt wurden, präsentiert. Das Quellverhalten und die mechanischen Eigenschaften wurden analysiert. Sowohl die Hydrophilie des Netzwerkes als auch die Vernetzungsdichte beeinflusste das Quellverhalten und die mechanische Festigkeit stark. Alle Hydrogele zeigten gute Zellverträglichkeit. Die Hydrogele basierend auf MeOx und EtOx wurden außerdem mit den Farbstoffen Fluorescein und Methylenblau beladen. Es wurde beobachtet, dass von den beiden Farbstoffen die Aufnahme des hydrophileren Farbstoffs Fluorescein stärker vom Quellungsgrad des Hydrogels abhing. Hingegen war die Aufnahme des hydrophoberen Farbstoffs Methylenblau weniger davon abhängig wie sehr das Hydrogel quellen konnte, sondern stärker von der Hydrophilie des Hydrogel-Netzwerkes. Um die potenzielle Anwendung als Knorpelkleber zu testen, wurden (biohybrid) Hydrogele basierend auf Catechol-funktionalisiertem Copolymeren mit und ohne zusätzliches Fibrinogen und dem Oxidationsmittel Natriumperiodat hergestellt. Das System war durch die eingebauten Ester Vernetzungspunkte abbaubar. Das Quellverhalten und die mechanischen Eigenschaften wurden charakterisiert. Wie zu erwarten, zeigten Hydrogele mit stärkerer Vernetzung eine geringe Quellung und einen höheren elastischen Modulus. Die Zugabe von Fibrinogen jedoch erhöhte die Elastizität des Netzwerkes, welches förderlich für die avisierte Anwendung als Knorpelkleber sein kann. Die biologische Auswertung zeigte, dass die Ester-haltigen, abbaubaren Vernetzungspunkte von großem Vorteil sind. Die Chondrozyten konnten ohne Probleme den Defektspalt überbrücken, was nicht möglich war, sobald keine Ester Funktionalitäten im Hydrogel eingebunden waren. Zuletzt wurden verschiedene Möglichkeiten Peptid-Polymer Konjugate zu synthetisieren präsentiert. Zum einen wurden Peptide mit der Thiolgruppe des endständigen Cysteins an die Vinyl Seitenkette der P(EtOx-co-ButEnOx) Copolymere mittels radikalischer Thiol-en Chemie angebunden. Des Weiteren wurde ein zyklischer Thioester, das Thiolacton, und eine Azlacton Funktionalität verwendet, um ein Modell Peptid mittels nativer chemischer Ligation zu binden. Die zwei zuletzt genannten Strategien, um Peptide an Polymere zu binden, sind besonders interessant, da hier ein beziehungsweise im Fall der Thiolacton Funktionalität zwei freie Thiole an der Bindungsstelle nach der Reaktion entstehen. Diese könnten genutzt werden, um zum Beispiel über Thiol-en Chemie Peptid-haltige Hydrogele herzustellen. Zusammenfassend zeigen seitenkettenfunktionale Poly(oxazolin) Copolymere ein großes Potenzial für biomedizinische Anwendungen. Die vielen verschiedenen Seitenkettenfunktionalitäten können durch das passende Monomer oder durch Post-Polymerisationsfunktionalisierung eingebracht werden, wie in dieser Arbeit gezeigt. Durch ihre Multifunktionalität können Hydrogel Charakteristika, wie der Vernetzungsgrad und die mechanische Festigkeit, fein eingestellt und angepasst werden, je nach Anwendungsbereich im menschlichen Körper. Die entwickelten chemoselektiven und orthogonalen Reaktionswege können in der Zukunft genutzt werden, um Polymer Konjugate zu synthetisieren, welche zum Beispiel für das Drug Delivery oder im Bereich der Geweberegneration zum Einsatz kommen.

<p> The ability of a never-dried paper web on a paper machine to resist breakage is commonly referred to as paper wet-web strength. Low wet-web strength can lead to frequent breaks which interrupt production and lower paper machine efficiency. Currently, no commercial products provide the function of enhancing wet-web strength. Boronic acid derivatized polyvinylamine (PVAm-PBA) showed high instantaneous wet adhesion to regenerated cellulose membranes. The objective of the research summarized in this thesis was to determine the factors and mechanisms dictating PVAm-PBA adhesion to wet cellulose. In addition, narrowly distributed PVAm microgel was prepared and the wet adhesion of boronate-microgels to cellulose is reported.</p> <p> The phase behavior and surface tension of PVAm-PBA were measured as functions of pH and the degree of PBA substitution. The pH ranges over which phase separation occurred increased with PBA substitution. 150 kDa PVAm-PBA with 4% derivatization phased separated at pH 8.5 to 9.5.The copolymer based on 51 % substitution was insoluble over most of the pH range. The hydrophobicity of copolymers was reflected in the significant lowering of surface tension particularly at high pH. Additionally, fructose, which binds to borate, influenced the titration curves but did not influence surface tension.</p> <p> Pairs of wet, regenerated cellulose films were laminated with PVAm-PBA and the forces required to delaminate the never-dried laminates, were measured as functions of adhesive structure and application conditions. The greatest wet adhesion was obtained with 150 kDa PVAm with 16% of the amines bearing phenylboronic moieties. The pH at which the PVAm-PBA was adsorbed onto the cellulose was the dominant process parameter. The specific role of the phenyl boronic groups was illustrated in two ways: a) replacing the B(OH)2 with OH (i.e. phenol) gave much lower adhesion; and, b) wet adhesion was greatly reduced by the presence of sorbitol which effectively competes with cellulose for boronate binding sites.</p> <p> The interaction of boronate and cellulose was studied. Owing to poor solubility of cellulose, two model polymers: dextran and hydroxyethyl cellulose (HEC) and two saccharides: glucose and cellobiose were measured by boron NMR measurement, tensile extension, fluorescence spectra, viscometer and peeling test methods. In conclusion, carbon-1, 2 diols at one end of cellulose chain can react with boronic acid. By contrast, carbon-2, 3 diols, which are abundant on cellulose chains, cannot react with boronic acid and the other diols, such as carbon-3, 4 diols and carbon-4, 6 diols cannot react with boronic acid. The high adhesion of boronate containing polymers to cellulose membranes was attributed to boronate ester formation with the cellulose end groups on the membrane surfaces. </p> <p> Finally, a simple and effective methodology was demonstrated for the preparation of polyvinylamine microgel with a narrow distribution. Boronate derivatives of PVAm microgels displayed very high wet adhesion to cellulose over a broad pH range.</p> / Thesis / Doctor of Philosophy (PhD)

No description available.

No description available.

No description available.

No description available.