The aim of this thesis is to determine the feasibility of an injectable delivery system based on 5-ethylene ketal ε-caprolactone for localized delivery of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) for treating critical limb ischemia. HGF and VEGF were chosen because of their ability to simultaneously stimulate the proliferation and migration of endothelial cells, to initiate the formation of blood vessels and the recruitment of pericytes to stabilize the blood vessels. Homopolymer of 5-ethylene ketal ε-caprolactone and its copolymer with D,L-Lactide were synthesized by ring opening polymerization using hydrophobic initiator (octan-1-ol) or an hydrophilic initiator (MPEG), and stannous octanoate as a co-initiator/catalyst. The resulting polymers were amorphous and viscous liquids at room temperature. The viscosity, biodegradation rate, and release rate were varied by copolymerizing with D,L-lactide and/or initiating with MPEG or octan-1-ol. In vitro, the polymers degraded with surface erosion characterized by a nearly linear mass loss with time with no significant change in number average molecular weight and glass transition temperature. The ratio of EKC to DLLA in the copolymer remained the same throughout the degradation studies. A similar degradation mechanism was observed in vivo when the copolymer initiated with octan-1-ol was implanted subcutaneously in rats. In vivo, the polymer exhibited a moderate chronic inflammatory response, characterized by the presence of neutrophils, macrophages, fibroblasts and fibrous capsule formation. The inflammatory response decreased with time but was still on going after 18 weeks of subcutaneous implantation. Protein release from the polymer was transported by convection through the hydrated polymer region, at a rate determined by the osmotic pressure generated and the hydraulic conductivity of the polymer. Highly bioactive VEGF and HGF were released in a sustained manner, without burst effect for over 41 days when delivered simultaneously, using the osmotic release mechanism. VEGF was released at the rate of 36 ± 7 ng/day for 41 days, while HGF was released at the rate of 16 ± 2 ng/day for 70 days. Factors that influenced release of proteins were their solubility in the concentrated trehalose solution and hydraulic permeability of the polymer. This delivery system can serve as a potential vehicle for controlled release of VEGF and HGF for treating critical limb ischemia or the controlled release of other proteins for other clinical applications. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2012-05-23 10:18:48.307

La modélisation des phénomènes physiologiques induits par un écoulement, tels que l'écoulement sanguin au travers d'une sténose ou l'écoulement d'air lors de la production de parole, repose souvent sur des théories quasi-unidimensionnelles ou bi-dimensionnelles. Cependant, il est établi que le développement des couches limites dépend de la section transversale. Le but de cette thèse est de modéliser, simuler et caractériser l'importance potentielle de la section transversale sur les écoulements laminaires, contrôlés en pression, en l'absence ou en présence d'une constriction. Des coordonnées de translation sont utilisées pour obtenir des solutions pour des écoulement visqueux au travers d'une section de forme arbitraire. Cette paramétrisation est appliquée à la résolution des équations physiques pour des formes à deux et à trois dimensions. Un modèle d'écoulement simplifié quasi-tridimensionnel, qui prend en compte les pertes dissipatives par convection, la viscosité et la forme de la section est présenté et appliqué à la description de l'écoulement le long d'une sténose. Des données expérimentales et issues de simulations numériques sont collectées afin de caractériser l'influence de la forme de la section transversale dans le cas d'une constriction. simulation numérique sont comparées. / Physical models of physiological flow-induced phenomena, such as blood flow through a stenosis or air flow during human speech production, often rely on a quasi-one-dimensional or two-dimensional flow model, so that details of the cross section shape are neglected. Nevertheless, boundary layer development is known to depend on the cross section shape. The aim of this thesis is to model, simulate and characterize the potential impact of the cross section shape for pressure-driven laminar channel flow without and with constriction. Stretched coordinates are introduced to obtain viscous flow solutions for channels with an arbitrary cross section. The proposed cross section shape parametrization is applied to solve physical equations for two-dimensional and three-dimensional shapes. A simplified quasi-three-dimensional flow model, which accounts for kinetic losses, viscosity and the cross section shape, is presented and applied to describe the flow through a stenosis. Finally, flow data are gathered experimentally and numerically in order to characterize the influence of the cross section shape in the case of a constricted channel. Modeled, experimental and numerical data are compared.

Nanomaterials such as graphene oxide and carbon nanotubes, have demonstrated excellent properties for membrane desalination, including decrease of maintenance, increase of flux rate, simple solution casting, and impressive chemical inertness. Here, two projects are studied to investigate nanocarbon based membrane desalination. The first project is to prepare hybrid membranes with amyloid fibrils intercalated with graphene oxide sheets. The addition of protein amyloid fibrils expands the interlayer spacing between graphene oxide nanosheets and introduces additional functional groups in the diffusion pathways, resulting in increase of flux rate and rejection rate for the organic dyes. Amyloid fibrils also provide structural assistance to the hybrid membrane, which supresses cracking and instability of graphene oxide sheets. The second project is to fabricate polymer nanocomposite membranes with carbon nanotubes encapsulated by polymerized surfactants. The designed polymerizable surfactant forms lyotropic liquid crystalline mesophases in an aqueous medium with hexagonal packing of cylindrical micelles. The adsorption of surfactants on the surface of carbon nanotubes allows a stable dispersion of carbon nanotubes encapsulated in the cylindrical micelles, resulting in the ordered structure. After photo-polymerization, the composite membranes display enhanced dye rejection. Both projects have shown promising ways to improve membrane filtration by using nanomaterials.

The effects of system pressure on the performance stability of flow-through capacitive deionization (CDI) cells was investigated. Initial data showed that the highly porous carbon electrodes possessed air/oxygen in the micropores, and the increased system pressure boosts the gases solubility in saline solution and carries them out of the cell in the effluent. Upon applying a potential difference to the electrodes, capacitive-based ion adsorption occurs in competition with faradaic reactions that consume oxygen. Through the addition of backpressure, the rate of degradation decreases, allowing the cell to maintain its salt adsorption capacity (SAC) longer. The removal of oxygen from the pore space of the electrodes makes it no longer immediately accessible to faradaic reactions, thus hindering the rate of reactions and giving the competing ion adsorption an advantage that is progressively seen throughout the life of the cell. A quick calculation shows that the energy penalty to power the pump is fairly insignificant, especially in comparison to the cost of replacing the electrodes in the cell. Thus, operating at elevated pressures is shown to be cost effective for continuous operation through the reduced electrode replenishment costs.

This research was designed to provide an understanding of physical wind mechanisms within the complex terrain of the Great Valley of Eastern Tennessee to assess the impacts of regional air flow with regard to synoptic and mesoscale weather changes, wind direction shifts, and air quality. Meteorological data from 2008–2009 were analyzed from 13 meteorological sites along with associated upper level data. Up to 15 ancillary sites were used for reference. Two-step complete linkage and K-means cluster analyses, synoptic weather studies, and ambient meteorological comparisons were performed to generate hourly wind classifications. These wind regimes revealed seasonal variations of underlying physical wind mechanisms (forced channeled, vertically coupled, pressure-driven, and thermally-driven winds). Synoptic and ambient meteorological analysis (mixing depth, pressure gradient, pressure gradient ratio, atmospheric and surface stability) suggested up to 93% accuracy for the clustered results. Probabilistic prediction schemes of wind flow and wind class change were developed through characterization of flow change data and wind class succession. Data analysis revealed that wind flow in the Great Valley was dominated by forced channeled winds (45–67%) and vertically coupled flow (22–38%). Down-valley pressure-driven and thermally-driven winds also played significant roles (0–17% and 2–20%, respectively), usually accompanied by convergent wind patterns (15–20%) and large wind direction shifts, especially in the Central/Upper Great Valley. The behavior of most wind regimes was associated with detectable pressure differences between the Lower and Upper Great Valley. Mixing depth and synoptic pressure gradients were significant contributors to wind pattern behavior. Up to 15 wind classes and 10 sub-classes were identified in the Central Great Valley with 67 joined classes for the Great Valley at-large. Two-thirds of Great Valley at-large flow was defined by 12 classes. Winds flowed on-axis only 40% of the time. The Great Smoky Mountains helped create down-valley pressure-driven winds, downslope mountain breezes, and divergent air flow. The Cumberland Mountains and Plateau were associated with wind speed reductions in the Central Great Valley, Emory Gap Flow, weak thermally-driven winds, and northwesterly down sloping. Ridge-and-valley terrain enhanced wind direction reversals, pressure-driven winds, as well as locally and regionally produced thermally-driven flow.