Hydrogels are three dimensional, insoluble, porous and crosslinked polymer networks. Due to their high water content, they have great resemblance to natural tissues, and therefore, demonstrate high biocompatibility. The porous structure provides an aqueous environment for the cells and also allows influx of nutrients needed for cellular viability. In this study, a natural biodegradable material, agarose (Aga), was used and semi-interpenetrating networks (semi-IPN) were prepared with polymers having different charges, such as positively charged chitosan (Ch) and negatively charged alginate (Alg). Hydrogels were obtained by the thermal activation of agarose with the entrapment of Ch or Alg in the Aga hydrogel structures. Chemical composition of hydrogels were determined by ATR-FTIR examinations, mechanical properties of hydrogels were examined through compression tests, morphologies were confirmed by scanning electron microscopy (SEM) and confocal microscopy, thermal properties were evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Moreover, swelling ratios, water contact angles and surface free energies (SFE) were determined. Cell proliferation and cell migration within these hydrogels were examined by using L929 fibroblast cell line. MTS assays were carried out to observe the cell proliferation on hydrogels. Confocal microscopy was used in order to examine the cell behavior such as cell attachment and cell migration towards the hydrogels. It was observed that addition of positively charged Ch into agarose increased the ultimate compressive strength (UCS), decreased elastic modulus (E), increased the thermal stability and hydrophobicity of the semi-IPN hydrogels. On the other hand, addition of negatively charged Alg into agarose decreased UCS, E, thermal stability and hydrophilicity. Cell-material interaction results showed that Aga hydrogels in tissue engineering applications was improved by adding different charged polyelectrolytes. Cell migration within Aga hydrogels was enhanced by adding Ch, and hindered by addition of Alg. Maximum cell proliferation and maximum penetration of the cells were obtained with the Ch/Aga hydrogels most probably due to attraction between the negatively charged cell surface and the positively charged Ch/Aga hydrogel surface. It was shown that cell interaction of agarose hydrogel scaffolds could be enhanced by introducing chitosan within the agarose hydrogels and obtained structures could be candidates for tissue engineering applications.

Zeolite A membranes have great potential in pervaporation separation of ethanol/water mixtures with high flux and selectivity. Zeolite membranes usually synthesized from hydrogels in batch systems. In recent years, zeolite membranes are prepared in semicontinuous, continuous and recirculating flow systems to allow the synthesis of zeolite membranes with enlarged surface areas and to overcome the limitations of batch system at industrial level production. The purpose of this study is to develop a synthesis method for the preparation of good quality zeolite A membranes in a recirculated flow system from hydrogels and to test the separation performance of the synthesized membranes by pervaporation of ethanol/water mixture. In this context, three different experimental synthesis parameters were investigated with zeolite A membranes synthesized in batch system. These parameters were the composition of the starting synthesis hydrogel, silica source and the seeding technique. Syntheses were carried out using hydrogels at atmospheric pressure and at 95 &deg / C. The membranes were characterized by X-ray diffraction, scanning electron microscopy and pervaporation of 90 wt% ethanol-10 wt% water mixtures. v Pure zeolite A membranes were synthesized both in batch and flow systems. The membranes synthesized in batch system have fluxes around 0.2-0.3 kg/m2h and selectivities in the range of 10-100. Membranes with higher selectivities were obtained in batch system by using waterglass as silica source, seeding by dip-coating wiping method, and with a batch composition of 3.4Na2O:Al2O3:2SiO2:155H2O. The membranes prepared in flow system have higher pervaporation performances than the ones prepared in batch system in considering both flux and the selectivity. Fluxes were around 0.3-3.7 kg/m2h and selectivities were in the range of 102-104 for the membranes prepared in flow system which are comparable with the data reported in literature for batch and flow systems. A high quality zeolite A membrane was also synthesized from 3.4Na2O:Al2O3:2SiO2:200H2O hydrogel at 95 &deg / C for 17 hours in flow system. Pervaporation flux of this membrane was 1.2 kg/m2h with a selectivity &gt / 25,000 at 50&deg / C. Although the synthesis method is resulted with high quality membrane, reproducibility of the synthesis method is poor and it should be improved.

Acrylamide based hydrogels were synthesized through copolymerization reaction of allyl methacrylate with acrylamide. Copolymerization reactions were carried out with solution polymerization in tetrahydrofuran by using &alpha / -&alpha / -azoisobutyronitrile as an initiator at 60 0 C. Three copolymer compositions were studied having 5, 15, 25 molar percentage of allyl methacrylate as feed concentrations. The synthesized copolymers were characterized by FTIR, NMR, DSC, TGA and GPC. 1H-NMR spectra were used to confirm the chemical structures of the copolymers and to determine the comonomer compositions of the copolymers. DSC and TGA analysis were conducted to determine the thermal properties of the copolymers and TGA results showed that copolymers have two step degradation behavior. Molecular weights of the copolymers were determined by GPC. Swelling capacities of the obtained hydrogels were investigated and swelling capacity of the gels reached to 77% as maximum value.

The studies of the dynamics, phase behavior, interparticle interactions, and hydrodynamics of stimuli-responsive pNIPAm-co-AAc microgels were described in this thesis. Due to their responsiveness to external stimuli, these colloidal particles serve as excellent model systems to probe the relationship between colloidal interactions and phase behavior. As a first step, we established our core experimental methodology, by demonstrating that particle tracking video microscopy is an effective technique to quantify various parameters in colloidal systems. Then we used the technique in combination with a microfluidic device that provides in situ control over sample pH to probe the phase behavior of pNIPAm-co-AAc microgel suspensions. In essence, the experimental set-up enables changes in effective particle volume fractions by changing pH, which can be used to construct the phase diagram. In order to explain the unique features of the microgel phase diagram, we measured the underlying pairwise interparticle potential of pNIPAm-co-AAc microgels directly in quasi-2D suspension and proved that the interactions are pH dependent and can range from weakly attractive to soft repulsive. Finally, the hindered Brownian diffusion due of colloidal particles confined by hard walls was investigated systematically and striking differences between hard sphere and soft sphere were found, with soft pNIPAm-co-AAc microgels showing surprising mobility even under strong confinement.

Craniosynostosis is the premature fusion of one or more cranial sutures in the developing skull. If left untreated, craniosynostosis can result in developmental delays, blindness, deafness, and other impairments resulting from an increase in the intracranial pressure. In many cases, the treatment consists of complex calvarial vault reconstruction with the hope of restoring a normal skull appearance and volume. Re-synostosis, the premature re-closure following surgery, occurs in up to 40% children who undergo surgery. If this occurs, a second surgery is needed to remove portions of the fused skull in an attempt to correct the deformities and/or relieve an increase in intracranial pressure. These subsequent surgeries are associated with an incredibly high incidence of life threatening complications. To address this unmet clinical need we have developed strategies to delay the post-operative bone growth in a clinically relevant murine model of re-synostosis. The overall objective of this thesis was to develop a hydrogel based therapy to delay rapid bone regeneration in a murine model of re-synostosis. The overall hypothesis was that delivery of key BMP inhibitors involved in regulating normal suture development and regeneration will delay the rapid bone growth that in seen in a pediatric murine model of re-synostosis. The overall approach is to use micro-computed tomography (µCT) to determine the time course of suture fusion and to identify genes associated with key developmental time points, to develop a pediatric specific mouse model that displays rapid re-synostosis, and lastly to develop a hydrogel based therapy to delay the re-synostosis of this cranial defect.

Quellfähige Verbundwerkstoffe aus Ton und Polyakrylamid können große Quantitäten von Wasser absorbieren, behalten aber dabei eine hohe mechanische Festigkeit und gute Dämpfungseigenschaften und stellen daher eine neue Klasse von Hydrogelen mit potentiell interessanten technologischen Eigenschaften dar. Solche superabsorbierende Verbundwerkstoffe (SAPC) werden durch Polymerisation mit einem Elektronenstrahl oder Bestrahlung mit UV-Licht hergestellt. Die Untersuchung der Eigenschaften von SAPC mit Hilfe von XRD, SEM, DSC, TGA, FTIR und NMR (27Al, 29Si und C) zeigen, dass in der SAPC-Struktur das Akrylamid (AM) mit Montmorillonit in dreierlei unterschiedlichen Weisen verbunden ist: a. AM interkaliert in den Zwischenschichtraum von Montmorillonit in bimolekularen Schichten, die durch van-der-Waals-Kräfte und Wasserstoffbindungen verknüpft sind; b. AM gebunden an der Oberfläche von Montmorillonit durch Wasserstoffbindungen; c. AM als freies Polymernetzwerk. Die Ergebnisse der rheologischen, mechanischen und thermischen Untersuchungen von SAPC zeigen eine völlig vernetzte Struktur mit vergleichsweise hoher mechanischer Festigkeit und thermischer Stabilität. Die Verwendung von SAPC bei der Ölgewinnung (Erhöhung der Ausbeute), im Umweltschutz (Reduzierung sauerer Berge), der Agri- und Silvikultur (Pflanzen, Samenbau), der petrochemischen Industrie (Entwässern), im Bauingenieurwesen (Zementbeimischung) und als Sensorsubstanz demonstriert, dass SAPC ein hohes Potential für umweltfreundliche und wirtschaftliche alternative Zwecke hat.

The Styx Mill Reserve is located in Belfast, Christchurch and is managed by the Christchurch City Council. Who aim to re-establish indigenous vegetation to large proportions of the area. These efforts have been successful in some sections of the Reserve; but large areas of the Reserve remain in grass and other weeds. The purpose of this investigation was to evaluate the presence of 5 hypothesised edaphic1 zones in a 10 ha study area, with a future aim of matching establishment practices to these edaphic sites. Findings indicated that all zones have significantly different vegetation and soil characteristics. Consequentially methods of native re-vegetation must be different in each zone if successful re-establishment of native species is to occur. Based on confirmed edaphic zones and client input, a site matched management plan and species list for one zone was developed. This aimed to increase the health and survival rates of plantings. Site modification followed techniques used at sites with similar conditions that have had successes in establishing woody vegetation. The effect of hydrogel on heath and survival levels was also trialled. To assess species suitability, five species were selected based on their abilities to survive the site conditions. Due to a combination of frost damage and ungulate browse, only totara survived and demonstrated good health scores. The frost factor is difficult to mitigate, hence species affected severely by frost are not recommended. The browse issue is easier to mitigate and it is felt that the two species heavily browsed, but not frosted are likely to be suitable. This resulted in ribbonwood, totara and kōhūhū being recommended. The time period did not allow assessment of the hydrogel treatment. Insufficient trial numbers exist to continue trials assessing future growth and survival rates over a longer time scale.

Drug delivery methods for the treatment of brain tumor cells have been both inefficient and potentially dangerous for cancer patients. Drug delivery must be done in a controlled manner so that the effective amount of medication is delivered to the patient and ensure over-dosage does not cause adverse side reactions in the patient. The focus of this investigation is to design a drug delivery system that would allow for site-specific administration of the drug, protection of the drug from the surrounding environment, and controlled sustained release of the drug. We have proposed a model that incorporates a niosome, which is a non-ionic surfactant vesicle, within a biodegradable polymer hydrogel. The drug is encapsulated in the niosome, and the niosome is embedded within a three-dimensional hydrogel network. It is therefore critical that the release rate of the drug from the niosome be studied. This investigation provides information about the release rate and behavior of the drug within the niosome as it is placed in a semi-permeable membrane. The niosome and dye solution in the cellulose membrane are placed in contact with water or PBS. Intensity measurements are taken using fluorescence spectrometry, and the readings are converted to concentration and moles values. The release rates of the dye from of the niosome and across the membrane are studied as the concentration data is collected over time. The results indicate that most of the niosomes will release their dye within ten hours. The water will create instability in the niosomes, while the PBS solution will maintain the stability of the niosomes. The concentration that diffuses across the cellulose membrane will steadily increase and can be predicted well by a simple diffusion model. We hope to use the information provided in this study to continue to design a drug delivery method that will stabilize the niosomes and allow for the maximum control over the release rate of the drug.

While a number of PEGylated proteins have been studied for injectable applications and reviewers have used this data to speculate possible oral delivery improvements, a detailed investigation of PEGylated insulin for oral delivery and the development of an optimized pH-sensitive carrier for PEGylated insulin conjugates had yet to be accomplished. In order to proceed with oral delivery study, improvements in yield, with respect to previous PEGylation methods were necessary to enable the completion of high throughput drug delivery studies. Subsequently, a reaction scheme for the covalent attachment of PEG to insulin using nitrophenyl carbonate-PEG was developed. It was demonstrated that this reaction occurred at a 1:1 ratio and was site specific at the B29Lys position. A P(MAA-g-EG) hydrogel carrier was developed to optimize loading and release behavior for PEGylated insulin. It was demonstrated that the density and length of polymer grafts affected both loading and release behavior of PEGylated insulin. The best performing grafted polymers had a 3:1 methacrylic acid: ethylene glycol (MAA:EG) ratio and achieved loading efficiencies from 96% to nearly 100%. With respect to release, polymer particles containing fewer, but longer grafts shown to release faster than polymers with shorter grafts with the same MAA:EG ratio. Finally, the effects of PEGylation on intestinal absorption was investigated using an intestinal epithelial model as well as a rat model. It was demonstrated that PEGylated insulin in the presence of P(MAA-g-EG) microparticles did not significantly alter the tight junctions over unmodified insulin. However, the conjugate permeabilities across the membrane were reduced. The pharmacological availability (PA) was then verified by injecting the insulin conjugates subcutaneously in fasted Sprague-Dawley rats. It was determined that PEG 1000 insulin (1KPI) had a PA roughly equivalent to insulin, while it was reduced by 59% for 2KPI and by 81% for 5KPI. The effectiveness of utilizing PEGylated insulin as an oral drug delivery candidate was evaluated with a closed loop intestinal study, in which PEGylated insulin or insulin in solution was delivered directly to the jejunum. It was shown that 1KPI and insulin performed identically; with a pharmacological availability of 0.56%. 2KPI, however improved the pharmacological availability of insulin by 2.8 times. These results demonstrate that PEGylation holds promise for improving the oral delivery of proteins. / text

The emerging class of biologic drugs, including proteins, peptides, and gene therapies, are widely administered by injection, despite potential systemic side effects. Rational design of targeted carriers that can be delivered non-invasively, with reduced side effects, is essential for the success of these therapies, as well as for the improvement of patient compliance and quality of life. One potential approach is to take advantage of specific physiological cues, such as enzymes, which would trigger drug release from a drug carrier. Enzymatic cleavage is highly specific and could be tailored for certain diseased tissues where specific enzymes are up regulated. Enzymatically-degradable hydrogels, which incorporate an enzyme- cleavable peptide into the network structure, have been extensively reported for releasing drugs for tissue engineering applications. These studies showed that a rapid response and corresponding drug release occurs upon enzyme exposure, whereas minimal degradation occurs without enzyme. Recently, Michael addition reactions have been developed for the synthesis of such enzymatically-degradable hydrogels. Michael addition reactions occur under mild physiological conditions, making them ideally suited for polymerizing hydrogels with encapsulated biologic drugs without affecting its bioactivity, as in traditional polymerization and particle synthesis. The focus of my research was to create enzymatically-degradable hydrogel microparticles, using Michael addition chemistry, to evaluate for use as an inhalable, disease-responsive delivery system for biologic drugs and nanoparticles. In this dissertation, I utilize bioconjugation and Michael addition chemistries in the design and development of enzymatically-degradable hydrogels, which may be tailored to a multitude of disease applications. I then introduce a new method of hydrogel microparticle, or microgel, synthesis known as the Michael Addition During Emulsion (MADE) method. These microgel carriers were evaluated in vitro, and found to exhibit triggered release of encapsulated biologic drugs in response to enzyme, no significant cytotoxic effects, and the ability the avoid rapid clearance by macrophages. Lastly, in vivo studies in mice were conducted, and microgels were found to exhibit successful delivery to the deep lung, as well as prolonged pulmonary retention after intratracheal aerosol delivery. In conclusion, a new class of enzymatically-degradable microgels were successfully developed and characterized as a versatile and promising new system for pulmonary, disease-responsive delivery of biologic drugs. / text