One of the main issues with the use of nickel titanium alloy (NiTi) implants in cardiovascular implants (stents) is that these devices must be of very high quality in order to avoid subsequent operations due to failing stents. For small stents with diameters below ca. 2 mm, however, stent characterization is not straightforward. One of the main problems is that there are virtually no methods to characterize the interior of the NiTi tubes used for fabrication of these tiny stents. The current paper reports on a robust hybrid actuator for the characterization of NiTi tubes prior to stent fabrication. The method is based on a polymer/hydrogel/magnetic nanoparticle hybrid material and allows for the determination of the inner diameter at virtually all places in the raw NiTi tubes. Knowledge of the inner structure of the raw NiTi tubes is crucial to avoid regions that are not hollow or regions that are likely to fail due to defects inside the raw tube. The actuator enables close contact of a magnetic polymer film with the inner NiTi tube surface. The magnetic signal can be detected from outside and be used for a direct mapping of the tube interior. As a result, it is possible to detect critical regions prior to expensive and slow stent fabrication processes.

Hydrophobic drug paclitaxel nanoparticles (PAX NPs) and pH sensitive hydrogels were prepared in this study to build a colon targeting nanoparticle based drug delivery system for oral administration. Negative charged PAX NPs at the size of 110 +/- 10 nm were fabricated, characterized and then encapsulated in synthetic / biomacromolecule shell chitosan, dextran-sulfate using a layer by layer (LbL) self-assembly technique. Surface modifications were performed by covalently conjugating with poly (ethylene glycol) (H2N-PEG-carboxymethyl, Mw 3400) and fluorescence labeled wheat germ agglutinin (F-WGA), so as to build a biocompatible and targeted drug delivery system. Extended release of drug paclitaxel can be realized by adding more polyelectrolyte layers in the shell. High cell viability with PEG conjugated and high binding capacities of WGA modified nanoparticles with Caco-2 cells were observed. Preliminary study on stability of the nanoparticles in suspension at different pH was also performed. Two dextran based pH sensitive and enzyme degradable hydrogels: dextran maleic acid (Dex-MA), and glycidyl methacrylated dextran (Dex-GMA) were synthesized for oral delivery of nanoparticles. Hydrogels of both kinds were stable in simulated gastric fluid, but were prone to swelling and degradation in the presence or absence of enzyme dextranase in simulated intestinal fluid. The release profiles of nanoparticles could be tuned from 5 hr to 24 hr periods of time with more than 85% of the nanoparticle released in the simulated intestinal fluid. The release of PAX NPs was completed with longer time periods (45 hr-120 hr). Two possible release mechanisms were discussed for Dex-MA and Dex-GMA-co-AA hydrogels respectively: degradation controlled, and diffusion controlled. These biodegradable hydrogels, which can release nanoparticles depending on pH changes, together with the biocompatible and targeted nanoparticles, may be suitable as a potential colon targeting system for oral delivery of drug nanoparticles.

Due to an increased environmental awareness and thus, concerns over the use of fossil-based monomer for polymer production, there is an ongoing effort to find alternatives to non-renewable traditional monomers. This has ushered in the rapid growth in the development of bio-based materials such as green monomers and biodegradable polymers from vegetable and animal resources. Glycerol, as a renewable bio-based monomer, is an interesting candidate for sustainable polymer production. Glycerol is a renewable material that is a by-product of the transesterification of vegetable oils to biodiesel. Utilization of the excess glycerol derived from the growing biodiesel industry is important to oleochemical industries. The main objective of this thesis was to produce high molecular weight polyglycerol from glycerol and synthesize stimuli-responsive polyglycerol hydrogels. The work began with an investigation of the step-growth polymerization of glycerol to relatively high molecular weight polyglycerol using several catalysts. The catalytic reaction mechanisms were compared and the polymer products were fully analyzed. High molecular weight partially branched polyglycerol with multimodal molecular weight distributions was obtained. The polymerization of glycerol proceeded fastest with sulphuric acid as catalyst as indicated by the highest observed conversion of monomer along with the highest molecular weights. Theoretical models were used to predict the gel point and to calculate monomer functionality. High molecular weight polyglycerol was used to synthesize novel stimuli-responsive hydrogels. Real-time monitoring of step-growth polymerization of glycerol was investigated using in-line and off-line Attenuated Total Reflectance/Fourier Transform infrared (ATR-FTIR) technique.

Spinal cord injury and stroke are two devastating neurological events that lack effective clinical treatments. Recent neuroregenerative approaches involving the delivery of cells or drugs to the injured tissue have shown promise, but face critical challenges to clinical translation. Herein, hyaluronan-methylcellulose (HAMC) hydrogels were investigated as a versatile means of overcoming the challenges facing central nervous system cell and drug delivery. HAMC was shown to support the viability of encapsulated human umbilical tissue-derived cells, demonstrating utility as a scaffold for therapeutic cell delivery to the injured spinal cord. In a drug delivery context, release of the neuroregenerative drug cyclosporin A from the hydrogel was tunable over 2-28 days and the drug diffused to the stem cell niche in the brain and persisted for up to 24 days at a stable concentration when the HAMC-based system was implanted epi-cortically. HAMC is thus a promising tool for emerging neuroregenerative therapies.

Spinal cord injury and stroke are two devastating neurological events that lack effective clinical treatments. Recent neuroregenerative approaches involving the delivery of cells or drugs to the injured tissue have shown promise, but face critical challenges to clinical translation. Herein, hyaluronan-methylcellulose (HAMC) hydrogels were investigated as a versatile means of overcoming the challenges facing central nervous system cell and drug delivery. HAMC was shown to support the viability of encapsulated human umbilical tissue-derived cells, demonstrating utility as a scaffold for therapeutic cell delivery to the injured spinal cord. In a drug delivery context, release of the neuroregenerative drug cyclosporin A from the hydrogel was tunable over 2-28 days and the drug diffused to the stem cell niche in the brain and persisted for up to 24 days at a stable concentration when the HAMC-based system was implanted epi-cortically. HAMC is thus a promising tool for emerging neuroregenerative therapies.

The search for cellulosic based products as a viable alternative for petroleum-based products was the impetus for covalently crosslinking lignocellulosic fibers and nanocellulose whiskers with poly(methyl vinyl ether) co maleic acid (PMVEMA) - polyethylene glycol (PEG). The lignocellulosics used were ECF bleached softwood (pine) and ECF bleached birch kraft pulp. This thesis also tests the hypothesis that water absorption and retention can be improved by grafting PMVEMA-PEG to the surface of ECF bleached kraft pulp hardwood and softwood fibers via microwave initiated crosslinking. The crosslinking of the PMVEMA to hardwood and softwood kraft ECF bleached pulp fibers resulted in enhanced water absorbing pulp fibers where the PMVEMA is grafted onto the surface of the fibers. The crosslinking was initiated both thermally and via microwave irradiation and the water absorption and water retention was measured as the percent of grafted PMVEMA. This was the first application of microwave crosslinking of pulp fibers with the goal of creating water absorbing pulp fibers. Ultimately, the water absorption values ranged from 28.70 g water per g dry crosslinked pulp fiber (g/g) to 230.10 g/g and the water retention values ranged from 26% to 71% of the water retained that was absorbed by the crosslinked pulp fibers. The microwave initiated crosslinked fibers had comparable results to the thermally crosslinked fibers with a decreased reaction time, from 6.50 min (thermal) to 1 min 45 sec (microwave). Cellulose nanowhiskers, crystalline rods of cellulose, have been investigated due to their unique properties, such as nanoscale dimensions, low density, high surface area, mechanical strength, and surface morphology and available surface chemistry. Prior to this study, the crosslinking of cellulose whiskers with the matrix via solution casting of liquid suspensions of whiskers and matrix had not been explored. The hypothesis to be investigated was that incorporating cellulosic whiskers with the PMVEMA-PEG matrix and crosslinking the whiskers with the matrix would yield films that demonstrate unique properties when compared to prior work of crosslinking of PMVEMA-PEG to macroscopic ECF bleached kraft pulp fibers. Solution cast composites of cellulose nanowhiskers-PMVEMA-PEG were crosslinked at 135 °C for 6.5 min and analyzed for crosslinking, thermal stability, strength and mechanical properties, whisker dispersion, and water absorption and uptake rates. The whisker-composites demonstrated unique properties upon crosslinking the whiskers with PMVEMA-PEG, especially the elongation at break and tensile strength upon conditioning of the final materials at various relative humidities. In addition, the whiskers improved the thermal stability of the PMVEMA-PEG matrix. This is significant as methods of improving processing thermal stability are key to developing new materials that utilize cellulose whiskers, PMVEMA, and PEG. This thesis addresses the hypothesis that cellulose nanowhiskers that are crosslinked with a matrix can create new whisker-matrix composites that behave differently after crosslinking.

Tissue-engineering (TE) is one of the most innovative approaches for tackling many diseases and body parts that need to be replaced, by developing artificial tissues and organs. For this, tissue scaffolds play an important role in various TE applications. A tissue scaffold is a 3D (3D) structure with interconnected pore networks and used to facilitate cell growth and transport of nutrients and wastes while degrading gradually itself. Many fabrication techniques have been developed recently for incorporating living cells into the scaffold fabrication process and among them; dispensing-based rapid prototyping techniques have been drawn considerable attention due to its fast and efficient material processing. This research is aimed at conducting a preliminary study on the dispensing-based biofabrication of 3D cell-encapsulated alginate hydrogel scaffolds. Dispensing-based polymer deposition system was used to fabricate 3D porous hydrogel scaffolds. Sodium alginate was chosen and used as a scaffolding biomaterial. The influences of fabrication process parameters were studied. With knowledge and information gained from this study, 3D hydrogel scaffolds were successfully fabricated. Calcium chloride was employed as crosslinker in order to form hydrogels from alginate solution. The mechanical properties of formed hydrogels were characterized and examined by means of compressive tests. The influences of reagent concentrations, gelation time, and gelation type were studied. A post-fabrication treatment was used and characterized in terms of strengthening the hydrogels formed. In addition, the influence of calcium ions used as crosslinker on cell viability and proliferation during and after the dispensing fabrication process was examined and so was the influence of concentration of calcium solutions and exposing time in both media and alginate hydrogel. The study also showed that the density of encapsulated cells could affect the viscosity of alginate solution. In summary, this thesis presents a preliminary study on the dispensing-based biofabrication of 3D cell-encapsulated alginate hydrogel scaffolds. The results obtained regarding the influence of various factors on the cell viability and scaffold fabrication would form the basis and rational to continue research on fabricating 3D cell-encapsulated scaffolds for specific applications.

Due to an increased environmental awareness and thus, concerns over the use of fossil-based monomer for polymer production, there is an ongoing effort to find alternatives to non-renewable traditional monomers. This has ushered in the rapid growth in the development of bio-based materials such as green monomers and biodegradable polymers from vegetable and animal resources. Glycerol, as a renewable bio-based monomer, is an interesting candidate for sustainable polymer production. Glycerol is a renewable material that is a by-product of the transesterification of vegetable oils to biodiesel. Utilization of the excess glycerol derived from the growing biodiesel industry is important to oleochemical industries. The main objective of this thesis was to produce high molecular weight polyglycerol from glycerol and synthesize stimuli-responsive polyglycerol hydrogels. The work began with an investigation of the step-growth polymerization of glycerol to relatively high molecular weight polyglycerol using several catalysts. The catalytic reaction mechanisms were compared and the polymer products were fully analyzed. High molecular weight partially branched polyglycerol with multimodal molecular weight distributions was obtained. The polymerization of glycerol proceeded fastest with sulphuric acid as catalyst as indicated by the highest observed conversion of monomer along with the highest molecular weights. Theoretical models were used to predict the gel point and to calculate monomer functionality. High molecular weight polyglycerol was used to synthesize novel stimuli-responsive hydrogels. Real-time monitoring of step-growth polymerization of glycerol was investigated using in-line and off-line Attenuated Total Reflectance/Fourier Transform infrared (ATR-FTIR) technique.

The primary objective of this study was to quantify and characterise lipid deposition on soft (hydrogel) contact lenses, particularly those containing siloxane components. Studies involving a variety of <em>in vitro</em> doping and <em>in vivo</em> worn contact lenses were undertaken, in which lipid deposition was analyzed by either TLC or HPLC. Specific experiments were completed to optimize a method to extract the lipid from the lens materials, to compare the total lipid deposition on nine different hydrogel lenses and to analyze the effect that lipid deposition had on wettability. A method for extracting lipid from contact lenses using 2:1 chloroform: methanol was developed. This study also showed that siloxane-containing contact lens materials differ in the degree to which they deposit lipid, which is dependent upon their chemical composition. Small differences in lipid deposition that occur due to using variations in cleaning regimens were not identifiable through TLC, and required more sophisticated analysis using HPLC. Contact lens material wettability was found to be influenced by <em>in vitro</em> lipid deposition. Specifically, conventional hydrogels and plasma surface-treated silicone-hydrogel materials experienced enhanced wettability with lipid deposition. Reverse-phase HPLC techniques were able to quantify lipid deposits with increased sensitivity and accuracy. From the HPLC studies it was found that contact lens material, concentration of the lipid doping solution, and the composition of the lipid doping solution in <em>in vitro</em> deposition studies influenced the ultimate amount and composition of lipid deposits. <em>In vivo</em> HPLC studies showed that the final lipid deposition pattern was influenced by the interaction between the composition of the tear film and the various silicone hydrogel contact lens materials. In conclusion, HPLC analysis methods were more sensitive and quantitative than TLC. Lipid deposition was ultimately influenced by the concentration and composition of the lipid in the tear film and the contact lens material. Contact lens wettability was influenced by the presence and deposition of lipid onto the contact lens surfaces. Finally, this reverse-phase HPLC lipid analysis protocol was not the most sensitive, robust, or accurate. In the future, other methods of analysis should be explored.

Introduction Contact lenses suffer from the same problems of deposition that other biomaterials exhibit, being rapidly coated with a variety of proteins, lipids and mucins. The first event observed at the interface between a contact lens and tear fluid is protein adsorption. Protein deposits on contact lenses are associated with diminished visual acuity, dryness and discomfort and lid-related inflammatory changes. The aim of this thesis was to determine the quantity and the conformational state of lysozyme deposited on contact lens materials over various time periods and also to determine the clinical relevance of protein deposits on contact lenses. The specific aims of each chapter of this thesis were as follows: • Chapter 4: To determine the total lysozyme deposition on conventional and silicone hydrogel contact lens materials as a function of time by artificially doping lenses with 125I-labeled lysozyme. • Chapter 5: To determine the conformational state of lysozyme deposited on conventional and silicone hydrogel contact lens materials as a function of time using an in vitro model. • Chapter 6: To quantify the total protein, total lysozyme and the conformational state of lysozyme deposited on a novel, lathe-cut silicone hydrogel contact lens material after three-months of wear. • Chapter 7: To determine the relationship between protein deposition and clinical signs & symptoms after one-day wear of etafilcon lenses in a group of symptomatic and asymptomatic lens wearers. • Chapter 8: To determine the influence of individual tear proteins (lysozyme, lactoferrin and albumin) on the adhesion of Gram positive and Gram negative bacteria to conventional and silicone hydrogel contact lens materials. Methods • Chapter 4: Conventional hydrogel FDA group I (polymacon), group II (alphafilcon A and omafilcon A), group IV (etafilcon A and vifilcon A), polymethyl methacrylate and silicone hydrogel lens materials (lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A and senofilcon A) were incubated in a lysozyme solution containing 125I-labeled lysozyme for time periods ranging from 1 hour to 28 days. After each time period, lysozyme deposited on contact lens materials was determined using a Gamma Counter. • Chapter 5: Conventional hydrogel FDA groups I, II, IV and silicone hydrogel lens materials were incubated in lysozyme solution for time periods ranging from 1 hour to 28 days. After each time period, the lysozyme deposited on the lenses was extracted and the sample extracts were assessed for lysozyme activity and total lysozyme. • Chapter 6: 24 subjects completed a prospective, bilateral, daily-wear, nine month clinical evaluation in which the subjects were fitted with a novel, custom-made, lathe-cut silicone hydrogel lens material (sifilcon A). After 3 months of wear, the lenses were collected and total protein, total lysozyme and active lysozyme deposition were assessed. • Chapter 7: 30 adapted soft contact lens wearers (16 symptomatic and 14 asymptomatic) were fitted with etafilcon lenses. Objective measures and subjective symptoms were assessed at baseline and after hours 2, 4, 6 and 8. After 2, 4, 6 and 8 hour time points, lenses were collected and total protein, total lysozyme and active lysozyme deposition were assessed. • Chapter 8: Three silicone hydrogel (balafilcon A, lotrafilcon B & senofilcon A) and one conventional hydrogel (etafilcon A) lens materials were coated with lysozyme, lactoferrin and albumin. Uncoated and protein-coated contact lens samples were incubated in a bacterial suspension of Staphylococcus aureus 31 and two strains of Pseudomonas aeruginosa (6294 & 6206). The total counts and the viable counts of the adhered bacteria were assayed. Results • Chapter 4: Lysozyme accumulated rapidly on conventional hydrogel FDA group IV lenses, reached a maximum on day 7 and then plateaued with no further increase. PMMA showed a deposition pattern similar to that seen on lotrafilcon A and lotrafilcon B silicone hydrogel lenses. After 28 days, conventional hydrogel FDA group IV lenses deposited the most lysozyme. • Chapter 5: After 28 days, lysozyme deposited on group IV lenses exhibited the greatest activity. Lysozyme deposited on polymacon, lotrafilcon A and lotrafilcon B exhibited the lowest activity. Lysozyme deposited on omafilcon, galyfilcon, senofilcon, and balafilcon exhibited intermediate activity. • Chapter 6: The total protein recovered from the custom-made lenses was 5.3±2.3 µg/lens and the total lysozyme was 2.4±1.2 µg/lens. The denatured lysozyme found on the lenses was 1.9±1.0 µg/lens and the percentage of lysozyme denatured was 80±10%. • Chapter 7: Correlations between subjective symptoms and protein deposition showed poor correlations for total protein/ lysozyme and any subjective factor, and only weak correlations between dryness and active lysozyme. However, stronger correlations were found between active lysozyme and subjective comfort. • Chapter 8: Different tear proteins had varying effects on the adhesion of bacteria to contact lens materials. Lysozyme deposits on contact lenses increased the adhesion of Gram positive Staphyloccocus aureus 31 strain, while albumin deposits increased the adhesion of both the Gram positive Staphyloccocus aureus and Gram negative Pseudomonas aeruginosa 6206 & 6294 strains. Lactoferrin deposits increased the total counts of both the Gram positive and Gram negative strains, while they reduce the viable counts of the Gram negative strains. Conclusions • Chapter 4: Lysozyme deposition is driven by both the bulk chemistry and also the surface properties of conventional and silicone hydrogel contact lens materials. The surface modification processes or surface-active monomers on silicone hydrogel lens materials also play a significant role in lysozyme deposition. • Chapter 5: The reduction in the activity of lysozyme deposited on contact lens materials is time dependent and the rate of reduction varies between lens materials. This variation in activity recovered from lenses could be due to the differences in surface/ bulk material properties or the location of lysozyme on these lenses. • Chapter 6: Even after three-months of wear, the quantity of protein and the conformational state of lysozyme deposited on these novel lens materials was very similar to that found on similar surface-coated silicone hydrogel lenses after two to four weeks of wear. These results indicate that extended use of the sifilcon A material is not deleterious in terms of the quantity and quality of protein deposited on the lens. • Chapter 7: In addition to investigating the total protein deposited on contact lenses, it is of significant clinical relevance to determine the conformational state of the deposited protein. • Chapter 8: Uncoated silicone hydrogel lens materials bind more Gram positive and Gram negative bacteria than uncoated conventional hydrogel lens materials. Lysozyme deposited on contact lens materials does not possess antibacterial activity against all bacterial strains tested, while lactoferrin possess an antibacterial effect against certain Gram negative strains tested in this study. This thesis has provided hitherto unavailable information on contact lens deposition and its influence on subjective symptoms and bacterial binding. These results suggest that protein deposition has a significant potential to cause problems. Therefore, it is important that practitioners advise their patients regarding the importance of lens disinfection and cleaning and appropriate lens replacement schedules. These results will also be useful for the contact lens industry and the general field of biomaterials research.