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<p>I put department up there as Biomedical Engineering. The full title should be: School of Biomedical Engineering.</p> / <p>The work presented in this thesis was focused on the surface modification of biomaterials with combinations of polyethylene glycol (PEG) and bioactive molecules (protein anticoagulants) for improved blood compatibility. Since the fate of biomaterials in contact with blood depends significantly on plasma protein-surface interactions, the objective of this work was to reduce non-specific protein adsorption using PEG and to promote specific protein interactions that could inhibit clot formation using protein anticoagulants as modifiers.</p> <p>Two anticoagulant molecules were used in this work: hirudin, a specific inhibitor of thrombin and corn trypsin inhibitor (CTI), a specific inhibitor of clotting factor XIIa. Gold, used as a model substrate, was modified with PEG and anticoagulant molecules using two methods referred to as sequential and direct. In the sequential method PEG was first immobilized on the surface and then the bioactive molecule was attached (conjugated) to the PEG. In the direct method, a PEG-bioactive molecule conjugate was first formed and then immobilized on the surface. Surfaces were characterized by contact angle, ellipsometry and x-ray photoelectron spectroscopy (XPS). Uptake of the bioactive molecules was measured by radiolabeling. Biointeraction studies included plasma protein adsorption, bioactivity assays using chromogenic substrates and clotting time assays. For PEG-hirudin and PEG-CTI surfaces (both direct and sequential) the protein resistance was similar to that of the PEG-alone surfaces. Despite having a lower density of bioactive molecule (both hirudin and CTI), the sequential surfaces showed superior bioactivity compared to the direct ones.</p> <p>To determine the optimal ratio of free PEG and bioactive molecule-PEG conjugate on the surface (best combination of protein resistance and bioactivity), PEG-CTI was immobilized on gold substrate with varying ratio of conjugated to free PEG using both direct and sequential methods. As the ratio increased, protein resistance was maintained while specific interactions (bioactivity) increased. The optimal composition appeared to be where all PEG molecules are conjugated to a CTI molecule.</p> <p>In the final part of this project, PEG and CTI were immobilized on polyurethane as a material with applicability to medical device construction. A sequential method was developed for this substrate. Comparison of the PEG-CTI surface with PEG only or CTI only surfaces indicated that the combination of PEG-CTI was effective both in reducing non-specific protein adsorption and promoting the specific interactions of CTI with its target plasma protein, factor XIIa. In fact, the presence of PEG improved CTI interactions with FXIIa compared with CTI only surfaces. Thus, sequential attachment of PEG and CTI may be effective for modifying polyurethane surfaces used in blood-contacting medical devices.</p> / Doctor of Philosophy (PhD)

<p>The controlled synthesis of functional low molecular weight polyethylene and polyethylene mimics is important in tuning polymer properties and is of great industrial interests. Living polymerization is a method that allows for precise control in polymer structure. Although high molecular weight polymers with controlled structures can be efficiently produced via living polymerization, the production of low molecular weight polymers faces the challenges of the use of large amounts of expensive catalyst and the broadening of polydispersity.</p> <p>The synthesis of well-defined functional low molecular weight polyethylene and polyethylene mimics is studied. Promising polymerization systems, including living ring opening metathesis polymerization (ROMP), living coordination polymerization, coordinative chain transfer polymerization (CCTP), and living C1 polymerization, are identified and are analyzed based on product properties, efficiency, cost, and safety.</p> <p>Within the identified systems, living ROMP is selected for study due to the industrial relevance of ROMP polymers, the availability of raw materials, and the ease of reaction setup. The efficiency of ROMP is challenged by polydispersity broadening resulting from slow initiation and poor reactor volume efficiency due to its implementation as a solution polymerization process. The challenges are addressed by the use of excess phosphine and the realization of ROMP as a bulk polymerization process.</p> <p>Experimental results demonstrate that bulk ROMP with and without phosphines yield product with similar or enhanced molecular weight distribution control as solution ROMP. Kinetic studies confirm living polymerization behaviour of bulk ROMP. A mathematical model is developed for the first time using method of moments to describe the kinetics and development of molecular weight distribution of ROMP. The model is a useful tool in preliminary research and commercialization of ROMP. The success of bulk ROMP and the development of a representative model yield ROMP as a promising method for the production of low molecular weight polymers with controlled architecture.</p> / Master of Applied Science (MASc)

An advanced finite element (FE) model of the electrofusion welding of thermoplastic pipes has been developed using the ABAQUS FE package. The heat transfer analysis is coupled with thermal deformation analysis to include the time-dependent closure of the initial gap between the pipe and fitting. The effect of radial melt movement into the interface is modelled using a new `virtual material movement¿ technique. The predicted results (temperature distribution in the weld region, melt affected zones and gap closure time) are compared with experimental data and good agreement is found

Synthetic antioxidants have traditionally been added directly to food products in a single initial dose to protect against oxidation of lipids and generation of free radicals. Natural antioxidants have been shown to undergo loss of activity and become prooxidants at high concentrations; therefore, a need exists to develop active packaging which can gradually deliver antioxidants in a controlled manner. The objectives of this research were to (1) form and characterize cyclodextrin inclusion complexes with the natural antioxidants, alpha-tocopherol and quercetin, (2) incorporate cyclodextrin inclusion complexes of natural antioxidants into linear low density polyethylene (LLDPE), and (3) measure the release kinetics of inclusion complexes of natural antioxidants from LLDPE into a model food system. Cyclodextrin inclusion complexes of alpha-tocopherol and quercetin were formed by the coprecipitation method and characterized in the solid state by NMR, IR spectroscopy, and thermal analyses. Solid inclusion complex products of alpha-tocopherol:beta-cyclodextrin and quercetin:gamma-cyclodextrin had molar ratios of 1.7:1 as determined by UV spectrophotometry, which were equivalent to 18.1% (w/w) alpha-tocopherol and 13.0% (w/w) quercetin. Free and cyclodextrin complexed antioxidant additives were compounded with a twin-screw mixer into two LLDPE resin types followed by compression molding into films. Release of alpha-tocopherol and quercetin from LLDPE films into coconut oil at 30 °C was quantified by HPLC during 4 weeks of storage. The total release of alpha-tocopherol after 4 weeks was 70% from the free form and 8% from the complexed form averaged across both LLDPE resins. The mechanism by which alpha-tocopherol was released was modified due to its encapsulation inside the beta-cyclodextrin cavity within the LLDPE matrix as indicated by its diffusion coefficient decreasing by two orders of magnitude. Molecular encapsulation of natural antioxidants using cyclodextrins may be used as a controlled release mechanism within polymer food packaging to gradually deliver an effective antioxidant concentration to a food product, thereby, limiting oxidation, maintaining nutritional quality, and extending shelf life. / Ph. D.

Fouling properties of materials such as polyethylene glycol (PEG) have been extensively studied over the past decades. Traditionally, the factors believed to result in protein adsorption resistance have included i) steric exclusion arising from the compression of longer chains and ii) grafting density contribution which may provide shielding from the underlying material. Recent studies have suggested that PEG interaction with water may also play a role in its ability to resist protein adsorption suggesting that steric exclusion may not be the only mechanism occurring during PEG/protein interactions. Star-shaped PEG polymers have been utilized in protein adsorption studies due to their high PEG segment concentration, which allows to increase the PEG chain grafting density compared to that achieved with linear PEG chains. Most studies that have investigated the interactions of tethered linear and star-shaped PEG layers with proteins have considered linear PEG molecules with molecular weights several orders of magnitude smaller than those considered for star-shaped PEG molecules (i.e. 10 000 g/mol vs. 200 000 g/mol, respectively). Additionally, the star-shaped PEG molecules which have been considered in the literature had up to ~70 arms and were therefore modeled by hard-sphere like structures and low chain densities near the surface due to steric hindrance. This resulted in some difficulties to achieve grafted PEG chain overlap for star molecules. Here, triethoxysilane end-functionalized linear PEG molecules have been synthesized and utilized to form star-shaped PEG derivatives based on ethoxy hydrolysis and condensation reactions. This resulted in PEG stars with up to ~4 arms, which were found to result in grafted star-shaped PEG chains with significant chain overlap. Linear PEG derivatives were synthesized so that their molecular weight would match the overall molecular weight of the star-shaped PEG molecules. These 2 PEG molecular architectures were covalently self-assembled to hydroxylated silicon wafers and the thickness, grafting density, and conformation of these films were studied. The adsorption of human albumin (serum protein) on linear and star-shaped PEG films was compared to that obtained on control samples, i.e. uncoated silicon wafers. Both film architectures were found to significantly lower albumin adsorption. / Ph. D.

This dissertation describes the essential modeling components and techniques for building comprehensive polymer process models for metal-catalyzed polyolefin processes. The significance of this work is that it presents a comprehensive approach to polymer process modeling applied to large-scale commercial processes. Most researchers focus only on polymerization mechanisms and reaction kinetics, and neglect physical properties and phase equilibrium. Both physical properties and phase equilibrium play key roles in the accuracy and robustness of a model. This work presents the fundamental principles and practical guidelines used to develop and validate both steady-state and dynamic simulation models for two large-scale commercial processes involving the Ziegler-Natta polymerization to produce high-density polyethylene (HDPE) and polypropylene (PP). It also provides a model for the solution polymerization of ethylene using a metallocene catalyst. Existing modeling efforts do not include physical properties or phase equilibrium in their calculations. These omissions undermine the accuracy and predictive power of the models. The forward chapters of the dissertation discuss the fundamental concepts we consider in polymer process modeling. These include physical and thermodynamic properties, phase equilibrium, and polymerization kinetics. The later chapters provide the modeling applications described above. / Ph. D.

Properties of both chemical contaminants and polymers can impact contaminant diffusivity and solubility in new and aged polyethylene materials for pipes and geomembranes. Diffusivity, solubility, polymer and chemical properties were measured for thirteen contaminants and six polyethylene materials that were new and/or aged in chlorinated water. Tree regression was used to select variables, and linear regression was used to develop predictive equations for contaminant diffusivity and solubility in polyethylene. Organic contaminant properties had greater predictive capability than polyethylene properties. Model coefficients significantly changed between new materials to chlorine-aged materials, indicating changes of polyethylene properties impact the interaction between contaminants and polymers. The metallic flavor of copper in drinking water influences the taste of water and can cause the taste problems for water utilities. The mechanism of metallic flavor caused by these metals is related to free or soluble ions. Free copper concentrations were measured at different pH in diluted artificial saliva using a cupric ion selective electrode. Three major proteins in human saliva: α-amylase, mucin and lactoferrin, were added in the artificial saliva and the impacts on the chemical speciation of copper were analyzed. Inorganic saliva components, typically phosphate, carbonate and hydroxide combined with copper and greatly influenced the levels of free copper in the oral cavity. Proteins such as α-amylase, mucin and lactoferrin also impacted the chemical speciation of copper, with different affinity to copper. Mucin had the greatest affinity with copper than α-amylase. / Master of Science

Oxidative processes are linked to a number of major disease states as well as the breakdown of many materials. Of particular importance are reactive oxygen species (ROS), as they are known to be endogenously produced in biological systems as well as exogenously produced through a variety of different means. In hopes of better understanding what controls the behavior of ROS, researchers have studied radical chemistry on a fundamental level. Fundamental knowledge of what contributes to oxidative processes can be extrapolated to more complex biological or macromolecular systems. Fundamental concepts and applied data (i.e. interaction of ROS with polymers, biomolecules, etc.) are critical to understanding the reactivity of ROS. A detailed review of the literature, focusing primarily on the hydroxyl radical (HO•) and hydrogen atom (H•) abstraction reactions, is presented in Chapter 1. Also reviewed herein is the literature concerning high density polyethylene (HDPE) degradation. Exposure to treated water systems is known to greatly reduce the lifetime of HDPE pipe. While there is no consensus on what leads to HDPE breakdown, evidence suggests oxidative processes are at play. The research which follows in Chapter 2 focuses on the reactivity of the hydroxyl radical and how it is controlled by its environment. The HO• has been thought to react instantaneously, approaching the diffusion controlled rate and showing little to no selectivity. Both experimental and calculational evidence suggest that some of the previous assumptions regarding hydroxyl radical reactivity are wrong and that it is decidedly less reactive in an aprotic polar solvent than in aqueous solution. These findings are explained on the basis of a polarized transition state that can be stabilized via the hydrogen bonding afforded by water. Experimental and calculational evidence also suggest that the degree of polarization in the transition state will determine the magnitude of this solvent effect. Chapter 3 discusses the results of HDPE degradation studies. While HDPE is an extremely stable polymer, exposure to chlorinated aqueous conditions severely reduces the lifetime of HDPE pipes. While much research exists detailing the mechanical breakdown and failure of these pipes under said conditions, a gap still exists in defining the species responsible or mechanism for this degradation. Experimental evidence put forth in this dissertation suggests that this is due to an auto-oxidative process initiated by free radicals in the chlorinated aqueous solution and propagated through singlet oxygen from the environment. A mechanism for HDPE degradation is proposed and discussed. Additionally two small molecules, 2,3-dichloro-2-methylbutane and 3-chloro-1,1-di-methylpropanol, have been suggested as HDPE byproducts. While the mechanism of formation for these products is still elusive, evidence concerning their identification and production in HDPE and PE oligomers is discussed. Finally, Chapter 4 deals with concluding remarks of the aforementioned work. Future work needed to enhance and further the results published herein is also addressed. / Ph. D.