Healing large bone defects remains a clinical challenge. While autografts are the gold standard treatment for large bone defects, they are limited by availability and donor site pain. Growth factor treatments such as BMP therapy provide a promising alternative but are expensive and present clinical safety concerns, primarily due to delivery of BMPs at supraphysiological doses. Integrins are ECM receptors which mediate crucial cell functions such as adhesion and differentiation. Therefore, understanding the role of integrins in bone formation and directing desired interactions may enable modulation of host cell functions for therapeutic applications. In this work, beta 1 integrins were deleted in osteolineage cells of transgenic mice at three different stages of differentiation to elucidate their role in bone development. We also engineered bioartificial PEG-based matrices which target the pro-osteogenic alpha 2 beta 1 integrin to promote bone healing. Conditional deletion of beta 1 integrins in osteochondroprogenitor cells under the Twist 2 promoter resulted in severe pre-natal skeletal mineralization defects and embryonic lethality. Targeted deletion of beta 1 integrins in osterix-expressing osteoprogenitors resulted in growth abnormalities, reduced calvarial mineralization, impaired femur development, and tooth defects. However, mice lacking beta 1 integrins in osteocalcin-expressing osteoblasts and osteocytes displayed only a mild skeletal phenotype, indicating that beta 1 integrins play an important role in early skeletal development, but are not required for mature osteoblast function. PEG hydrogels functionalized with the integrin-specific GFOGER ligand enhanced bone regeneration, induced defect bridging in combination with low doses of rhBMP-2 and stimulated improved bone healing compared collagen sponges, which are the clinical standard delivery vector for BMP-2 therapy. These results suggest that treatment with bioartificial integrin-specific PEG hydrogels may be a promising clinical strategy for bone regeneration in large bone defects.

Health monitoring of aeronautic structures and human beings is becoming crucial because of the human safety issues. In this thesis integrated (IUTs) and flexible ultrasonic transducers (FUTs) have been developed using a sol-gel spray piezoelectric film fabrication technology. IUTs can be fabricated directly onto the structures with curved surfaces even on-site. FUTs were made using membrane substrates of thickness less than 75 mum. In-situ monitoring of AI airframe thickness was carried out and the thickness measurement accuracy was better than 36 mum and 41 mum for IUT and FUT, respectively. The thickness of the ice on top of the AI airframe was also measured. Two crucial piezoelectric constants d33 and d31 of the composite film were measured with laser interferometer and optical coherence tomography system, respectively. Pulse and breath of a human being were also monitored using flexible piezoelectric membrane sensors. In addition, bones in human body were observed using FUTs as well and their performance is comparable to that of commercial ultrasonic transducers.

Interactions of colloidal particles with surfaces occur in natural and engineered systems, and they influence the transport of contaminants through diffusion, aggregation, filtration, and sedimentation. To quantify the transport and fate of colloidal particles and their influence on environmental systems, it is important to understand their interactions with surfaces. These interactions are influenced by physical and chemical surface properties such as hydrophobicity, charge density, and roughness, as well as environmental conditions such as relative humidity (RH). In atmospheric systems, RH induces the capillary force and also influences the contributions of van der Waals and electrostatic forces. To investigate the role of surface properties and RH in the interaction of colloidal particles with surfaces, atomic force microscopy was employed to measure the adhesion and friction forces of colloidal particles including Bacillus thuringiensis spores, silica, and gold at various experimental conditions with several types of surfaces including mica, silica, and radioactive gold. Contributions to the adhesion force by van der Waals, capillary, and electrostatic forces were theoretically calculated and compared to measured forces. Through experimental results and theoretical studies, it was identified how surface properties of interacting surfaces and experimental conditions influence the interfacial interactions of colloidal particles in atmospheric systems. The role of RH in adhesion and friction depends on the hydrophobicity or contact angles of interacting surfaces and surface roughness. Relative humidity also influences the contribution of electrostatic force to the total adhesion force by screening the strength of surface potential or providing a passage for charge leakage. The results of this thesis provide a better understanding of particulate processes that are influenced by the interactions of colloidal particles with surfaces and can be useful in monitoring and control of contamination in atmospheric systems.

The increasing production and usage of engineered nanoparticles has raised concerns about potential ecological and human exposures and the risks these novel materials may pose. Nanoparticles are often manufactured with an organic macromolecular coating, and they will attain further coatings of adsorbed natural organic matter (NOM) in the environment. The overall objective of this thesis is to improve our ability to quantify the effects of adsorbed coatings on nanoparticle fate in the environment. The physicochemical properties of the coating or the adsorbing macromolecule are expected to strongly mediate the surface interactions, and hence the environmental fate, of coated nanoparticles. To this end, this research focuses on assessing a coating characterization method and applying extensive characterization of NOM coatings to enable the development of correlations to predict nanoparticle deposition onto model environmental surfaces and aggregation. The first objective is to assess the applicability of a soft particle electrokinetic modeling approach to characterize adsorbed layer thickness, which contributes to repulsive steric forces that will affect nanoparticle deposition. A statistical analysis determined that high uncertainty in fitted layer thicknesses will limit this approach to thin, low-charged coatings (for which it may be advantageous to typical sizing methods such as dynamic light scattering). Application of this method in experimental studies further confirmed the model limitations in estimating layer thicknesses and the inability of this measurement (and other commonly measured properties) to fully explain nanoparticle deposition behavior. These results demonstrated the need for improved detail and accuracy in coating characterization. The second objective is to correlate the properties of NOM to its effects on gold nanoparticle aggregation, with particular focus on the role of heterogeneity or polydispersity of the NOM molecular weight. Multiple types of NOM collected from representative water bodies and soils were used, both in whole and separated into molecular weight (MW) fractions, and characterized for chemical composition and MW distribution. While average MW of the NOM provided good correlation with aggregation rate, the highest MW components were found to contribute disproportionately in stabilizing nanoparticles against aggregation, highlighting the importance of measuring and accounting for high MW components to explain nanoparticle aggregation. However, an outlier from the MW trend was identified, emphasizing the need for additional characterization (e.g. of reduced sulfur content or the conformation of the adsorbed NOM) to fully explain the effects of NOM on nanoparticle aggregation. Altogether, this research provides novel knowledge that will guide future application of characterization methods to predict attachment processes for coated nanoparticles in the environment.

Increased demand for rare earth elements (REEs) for applications in modern technologies has led to an increase in REE exploration. Several deposits are expected to begin mining within a decade, but few studies have examined the possible environmental effects created by these mines. Metal toxicity is thought to be greater in aqueous environments when metals occur as free ions rather than complexes, and the speciation can also impact the treatment technologies utilized to reduce metal concentrations. This research investigates the mineralogical source of REEs and the mechanism of REE mobility in low-temperature waters that have interacted with pilot plant tailings from the Nechalacho deposit, Northwest Territories. The Nechalacho deposit is owned by Avalon Rare Metals Inc. and located approximately 100 km east of Yellowknife. The deposit is hosted within a hydrothermally altered layered nepheline-sodalite syenite in the peralkaline Blatchford Lake complex. The main REE ore minerals are zircon, fergusonite, allanite, monazite, bastnäsite, and synchisite-parasite. Characterization of the tailings using mineral liberation analyzer (MLA) show that the ore minerals are fine grained and well liberated. Bastnäsite and synchisite-parasite are the only potentially soluble ore minerals at low temperature and near-neutral pH. Shake flask experiments were designed to simulate the interaction of tailings with three different leach waters to identify soluble phases and mobile elements. Decanted solutions from the shake flasks were filtered to 0.45µm and 0.01µm. Speciation modelling of the 0.01µm filtrate suggests that carbonate ligands will form the dominant complexes with the REEs, and <2% occur as free metal ions. Higher proportions of LREEs (1-6%) occur as free metal ions than HREEs (<1%) and LREEs occur in higher concentrations (2 to 8 times greater) than the HREE. REEs were found in the colloidal fraction ([REEcolloid] = [REE0.45µm] – [REE0.01µm]). Ionic strength is the dominant control on distribution of REEs between colloidal and dissolved fraction. Colloids captured on filters from ultrafiltration analyzed using scanning electron microscopy and synchrotron microanalysis show REEs are hosted in colloidal rare earth minerals (e.g. zircon) and also show colloidal humic acid, Fe-oxides and Mn-oxides. Speciation modeling shows that REE sorption to these phases is probable. / Thesis (Master, Geological Sciences & Geological Engineering) -- Queen's University, 2014-05-28 11:06:41.351

The research described covers fundamental studies of environmentally-responsive microgel-based thin films as a function of film architecture, microgel chemistry, film thickness, and environmental stimulus. Studies of multi-layer microgel thin films were conducted primarily using atomic force microscopy (AFM), quartz crystal microgravimetry (QCM), and surface plasmon resonance (SPR), each of which probed different aspects the film architecture as a function of pH of the environment around the film. Binary thin films were constructed by changing the ratios and composition of the microgels in solution to create multi-functional thin films for surface modification applications and were studied using AFM. The basic understanding of how these components create films at surfaces gives us insight into how the films perform and will allow for greater diversity without the guesswork. The morphology of films created from microgels with a degradable cross-linker was examined by AFM as a function of degradation of the particles structure. This thesis focuses mainly on very thin microgel films (<5 layers) studied using QCM, SPR, and AFM. Additional studies involving the characterization of semi-soft colloidal paint-on photonics are discussed in Appendix A.

Poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-AAc) copolymeric multi-responsive microgels demonstrate responsivity to temperature, pH, and ionic strength. A temperature-programmed polymerization protocol is proposed for the synthesis of large pNIPAm-AAc microgel particles with a hydrodynamic diameter of 2~5 μm. Immediately after preparation of concentrated pNIPAm-AAc dispersions in closed system, the average hydrodynamic diameter is smaller than the unperturbed diameter probably due to osmotic de-swelling effect. During the aging process, pNIPAm-AAc microgel particles start to swell while their dynamics slow down. The snapshots of phase behavior of pNIPAm-AAc microgel dispersions at different pH values are illustrated. The formation of crystalline phase should follow a nonergodic path in which microgel particles swell to the extent that they build up weak attractive interaction to allow them to associate while maintaining the opportunity of rearrangement to minimize local Gibbs free energy. The age-dependent thermostability of pNIPAm-AAc microgel dispersions suggests strong attractive interactions evolve between particles during aging-convoluted crystallization. Finally, to introduce multiple biological "handle"s on the microgel particles for biomedical applications, the Cu(I)-catalyzed azide-terminal alkyne 1,3-dipolar cycloaddition, also called Sharpless-Meldal "click" reaction, is used to functionalize pNIPAm-AAc microgel particles.

Colloidal particles are small particles ranging in size from nanometres to micrometres suspended in a fluid. Amongst many scientific and biological applications, they have been used to model crystallisation, vitrification, and particle interactions along with the use of colloidal model systems for the study of the fundamental nature of the fluid-crystal and fluid-glass phase transitions. It has been shown that colloidal particles can be trapped and manipulated using strongly-focused light beams known as optical tweezers, and this has paved the way for research into the area of micromanipulation using optical trapping. Holographic elements can replace multiple lenses in creating large numbers of optical tweezers and this is known as holographic optical trapping (HOT). A computer generated hologram can be designed to create large structured light fields, consisting of multiple foci, to enable trapping of multiple particles in arbitrary configurations. The overall aim of this project was to design, develop and test the suitability of a simple, inexpensive optical trapping arrangement suitable for multiple optical trapping. To achieve this, a theoretically-exact expression for the wavefront of a single point source was implemented in the coding scheme, allowing for the fast creation of multiple point sources suitable for holographic optical trapping experiments. Compensation for the spherical aberration present in the focusing optics was implemented into the coding scheme. Kodalith photographic film was chosen as the holographic recording medium for its high contrast and availability. The film has proven to be a successful medium, when used to record photographically-reduced images of high-quality printouts of the computed diffraction pattern, as it was able to successfully reproduce complex light fields. It is believed that this will be the first time that this film has been implemented for optical trapping purposes. The main limitations concerning the performance of the holograms recorded on Kodalith were the phase nonuniformities caused by unevenness in the film thickness which resulted in a failure to separately resolve light traps separated by less than about 5 (Mu)m. Index matching of the film between sheets of flat glass helped to compensate for these limitations. Holographic optical trapping was successfully observed using a variety of different initial beam powers, holographic aperture settings and light field configurations. Trapping experiments on of two types of particles (PMMA and polystyrene) were successfully conducted, with as little as ~ 150 (Mu)W per trap being required for multiple polystyrene trapping. However, particles were weakly trapped and were easily dislodged at these powers, and a higher power per trap of around 1 mW is preferred. The use of a relatively low numerical aperture (NA) 50 mm SLR lens for focusing the holographic optical traps was successful, proving that optical trapping can be conducted without the use of high NA microscope-objective lenses commonly used in other set ups. Holographic trapping of colloidal particles was successfully conducted at RMIT University for the first time proving the validity of the coding scheme, the recording method and the trapping arrangement.

Thesis (PhD)--University of South Australia, 2001.

An improved crystallisation spectrometer has been designed, built and tested. It is to be used by others to gain new knowledge about the solidification of matter by study of the crystallisation of hard sphere colloid samples that are an established model for the behaviour of some aspects of atoms. In this crystallisation spectrometer, expanded and collimated green laser light is Bragg scattered from the colloidal crystals as they form, and the diffracted light is focused by a liquid filled hollow glass hemispherical lens onto low cost CCD array detectors that are rotated about the optical axis to average the intensities around the whole Debye-Scherrer cone of scattered light. The temperature of the sample is controlled to +/-0.1„a, and because of the ability to change the refractive index of the sample particles with temperature, this is utilised to control the amount of scattering from the sample Also, this spectrometer uniquely exploits the refractive index match of the colloidal particles, the solvent, the bath liquid, and the glass used for both the sample bottle and the hollow glass hemisphere. A unique facility has been incorporated to permit tumbling of the sample prior to the measurement commencing to shear-melt any pre-existing crystals. This ensures that the sample is completely fluid and is at the correct temperature at the start of the measurement. The instrument is assembled on an optical table and is computer controlled. Results presented show that this new spectrometer with its use of the whole Debye-Scherrer cone of Bragg scattered light and other enhancements gives insight into the crystallisation process more than one order of magnitude of time earlier than previous light scattering experiments, providing new knowledge about the crystallisation process.