Browsing by Author "Davis, Richey M."
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- Adsorption in Confined Aqueous FilmsGaddam, Prudhvidhar Reddy (Virginia Tech, 2019-07-24)This thesis describes direct measurements of equilibrium adsorption of ions in thin (< 100 nm) aqueous films. Adsorption in thin films is important because it is through adsorption that the stability of colloidal suspensions is frequently tuned. The vast majority of measurements of adsorption to date have been to a single interfaces, whereas the subject of this thesis is adsorption in a thin film between two interfaces. There are two isolated interfaces when particles in a suspension are far apart, but during the collision, a thin film forms between the particles, and the properties of the thin film determines the stability of the colloid. Thus, adsorption in the thin film determines the stability of the colloidal dispersion. There is a distinct gap in the scientific literature concerning adsorption in thin films mainly because there is no technique for measuring such adsorption. To fill this gap in knowledge, I first developed of a technique to directly measure adsorption in thin films, and then applied this technique to explore the behavior of co-ions near charged interfaces as a function of bulk solution composition and the thickness of the film. The adsorption behavior of fluorescein, a di-anion, to negatively charged silica interfaces was studied in dilute electrolytes. The focus was on the effect of the electrostatic screening length, or Debye-length. The separation was measured using interference microscopy and the adsorption of fluorescein was measured using fluorescence microscopy. The Debye-length was altered by variation of the background salt (NaCl) concentration in dilute (<1 M) solution. The surface excess of adsorption for fluorescein was shown to depend on both the Debye-length and the separation distance between two interfaces. Increasing the Debye-length from 4 nm to 21 nm increased the plateau surface excess at large separations, and decreasing the separation lead to a monotonically decreasing surface excess. The surface excess varied over a range that scaled with the Debye-length. The results were compared to solution of the Poisson-Boltzmann model and good agreement was found between the model and the experiment. The effect of background salt concentration on fluorescein adsorption was also studied in concentrated electrolytes (2.5 – 10 M) for various monovalent salts (LiCl, NaCl and CsCl). The results showed that the fitted electrostatic screening length showed an opposite trend to predictions from Poisson-Boltzmann, with the screening-length increasing with increasing salt concentration. That is, the Debye-length prediction was quantitatively incorrect and predicts the incorrect trend. For example, in 10 M LiCl where the Debye-length is 0.1 nm, and therefore colloidal chemists would traditionally predict that double-layer forces are negligible, my results show that the actual decay length is about 10 nm, which is about the same as in 10-3 M LiCl solution. The rate of increase of screening-length as a function of concentration was also an ion specific effect. In addition, the results show that there is an inversion of the surface charge in concentrated salt solution. The original device on which all the above measurements were made had two limitations: (1) the maximum film thickness was 50 nm and (2) the film was asymmetric, which hampered calculation of the surface excess and increased the number of degrees of freedom in modeling of the adsorption. In the last part of my thesis, I describe development of a symmetric sample which (1) enables measurement of films up to 1 µm, (2) simplifies modeling of the optics by eliminating optical interference of the fluorescence excitation, and reduces the number of parameters when comparing to models.
- Adsorption of Novel Block Copolymers for Steric Stabilization and Flocculation of Colloidal Particles in Aqueous EnvironmentsKrsmanovic, Jody Lynn (Virginia Tech, 2003-01-15)The adsorption of several homopolymer polypeptides on Al2O3 and SiO2 particles and surfaces was investigated to identify possible anchor and tail blocks for brush-forming block copolypeptides. Poly-L-(glutamic acid) (GLU) and poly-L-(aspartic acid) (ASP) were found to adsorb on positively charged and nearly neutral Al2O3, while the GLU did not adsorb on negatively charged SiO2. Poly-L-proline (PRO) adsorbed only slightly on the alumina, but showed high affinity adsorption on silica. These results are useful in designing a brush forming block copolymer with the GLU acting as the anchor block and the PRO as the tail block. An important finding in this work is that these unstructured polypeptides, or proteins that only have primary and secondary structure, have adsorption behavior that is similar to that of synthetic polymers. The complexation between a random copolymer of two amino acids, glutamic acid and tyrosine, and poly(ethylene oxide) (PEO) was studied using an in-situ adsorption experiment. It was shown that the adsorption of the random copolymer greatly increased the adsorption of PEO. It was found that the conformation of the copolymer on the surface was controlled by the ionic strength, and the conformation of the adsorbed PEO was controlled by the PEO molecular weight. Both of these factors affected the molar complexation ratio between the PEO and the tyrosine repeat units. The adsorption of two novel triblock copolymers, with PEO tails and anionic hydrophobic center blocks, was studied on alumina and silica surfaces. On silica the adsorption was due to the PEO tails, resulting in low adsorbed amounts. The adsorption was much greater on alumina, indicating either brush formation on the surface or the adsorption of micelles, which are present in solution. The effect of adsorbed polymer on the steric stabilization of alumina particles was studied using sedimentation and electrophoretic mobility experiments. These results do not show conclusively that the triblock copolymer adsorption led to particle stabilization. It is possible that better colloid stabilization of the alumina may be realized by changing the triblock composition to get greater extension and higher packing of the PEO tails.
- Advanced Polymeric Membranes and Multi-Layered Films for Gas Separation and CapacitorsShaver, Andrew Thomas (Virginia Tech, 2016-06-30)The following studies describe the synthesis and properties of a family of poly(arylene ether ketone)s which are well known to have good thermal stability, mechanical durability, and other film properties. These poly(arylene ether ketone)s were functionalized with fluorine, oxidized, blended, and crosslinked to increase performance with focus on materials for polymeric capacitors and gas separation membranes. There is a need for polymeric capacitors with improved energy storage density and thermal stability. In this work, the affect of polymer molecular structure and symmetry on Tg, breakdown strength, and relative permittivity was investigated. A systematic series of four amorphous poly(arylene ether ketone)s was compared. Two of the polymers had symmetric bisphenols while the remaining two had asymmetric bisphenols. Two contained trifluoromethyl groups while the other two had methyl groups. The symmetric polymers had Tg's of approximately 160 °C while the asymmetric polymers showed higher Tg's near 180 °C. The symmetric polymers had breakdown strengths near 380 kV/mm at 150 °C. The asymmetric counterparts had breakdown strengths near 520 kV/mm even at 175 °C, with the fluorinated polymers performing slightly better in both cases. The non-fluorinated polymers had higher relative permittivities than the fluorinated materials, with the asymmetric polymers being better in both cases. Two amorphous, high glass transition, crosslinkable poly(arylene ether)s for gas purification membranes have been studied. The polymers were polymerized via step growth and contained tetramethyl bisphenol F and either 4,4'-difluorobenzophenone or 4,4'-dichlorodiphenylsulfone. The benzylic methylene group in tetramethyl bisphenol F can undergo oxidation reactions and crosslinking with UV light. The polymers were oxidized under two different conditions, one by chemical treatment using oxone and KBr and one by elevated thermal treatment in air. Thermogravimetric analysis, 1H-NMR and attenuated total reflectance Fourier transform infrared spectroscopy revealed the progress of the thermal oxidation reactions. Both polymers produced tough, ductile films and gas transport properties of the non-crosslinked linear polymers and crosslinked polymer was compared. Crosslinking was performed by irradiating polymer films for one hour on each side in air under a 100W high intensity, long-wave UV lamp equipped with a 365-nm light filter. The O2 permeability of tetramethyl bisphenol F containing non-crosslinked poly(arylene ether ketone) was 2.8 Barrer, with an O2/N2 selectivity of 5.4. Following UV crosslinking, the O2 permeability decreased to 1.8 Barrer, and the O2/N2 selectivity increased to 6.2. Poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) is a commercial polymer that is utilized for gas separation membranes. It has a relatively high free volume with high gas permeabilities but suffers from low gas selectivities. In this study, PPO polymers with number average molecular weights of 2000, 6000, 17,000, 19,000 and 22,000 were synthesized and blended with a poly(arylene ether ketone) synthesized from bisphenol A and difluorobenzophenone (BPA-PAEK) to make UV-crosslinkable films. The ketone and benzylic methylene groups on the BPA-PAEK and the PPO polymers respectively formed crosslinks upon exposure to broad wavelength UV light. The crosslinked blends had increased selectivities over their linear counterparts. DSC thermograms showed that the blends with all but the lowest molecular weight PPO had two Tg's, thus suggesting that two phases were present, one high in PBA-PAEK and the other high in PPO composition. The PBA-PAEK blend with the 2000 Mn PPO showed only one Tg between the two control polymers. Despite the immiscibility of these films, the gel fractions after UV exposure were high. Gel fractions as a function of the amount of the 22,000 Mn PPO were explored and did not show any significant change. UV spectroscopy of the individual components and the blends showed that more broad wavelength light was transmitted through the PPO component, so it was reasoned that films that was high in PPO composition crosslinked to deeper depths. The O2/N2 permeabilities and selectivities were measured for the linear and crosslinked films. Between the 33/67, 67/33, and 90/10 22k PPO/BPA PAEK crosslinked blended films, the 90/10 PPO/BPA PAEK gained the most selectivity and maintained a larger amount of its permeability. In comparison to commercial gas separation polymers, the non-crosslinked 33/67 22,000 Mn PPO/BPA PAEK blend outperformed polysulfone and cellulose acetate with a 2.45 degree of acetylation. Overall, we were able to blend a small amount of BPA PAEK with the commercially used PPO to create a mechanically robust crosslinked polymer film.
- Aggregation Behavior of Keratin Proteins Determined by Dynamic Light ScatteringEgert, Alexandra Marie (Virginia Tech, 2015-05-20)Keratin is a biomaterial derived from biological sources and can be used in a variety of medical applications. This study focuses on keratin derived from human hair. Unfortunately, there is not a lot of information in the literature describing how keratin reacts to subtle changes in an aqueous solution such as differences in pH, keratin concentration, buffer concentration, salt concentration, and temperature. To have a better understanding of this effect, dynamic light scattering was used to test the size ranges and volume percentages in each range. Dynamic light scattering shows the size of the keratin in each environment and its consistency with time. The results showed that there is a difference in keratin behavior between water and buffer solutions, but very subtle differences between each buffer, buffer concentration, keratin concentration, pH and temperature. Keratins aggregate extensively in un-buffered conditions (i.e. pure water), which has implications to both purification and fabrication of biomaterials as water is used extensively in these processes. Interestingly, there was little effect of keratin concentration, pH, and temperature on the buffers used in this study, suggesting there may be a wide range of conditions in which aggregation can be minimized.
- Alternative strategies to incorporate biomolecules within electrospun meshes for tissue engineringVaidya, Prasad Avdhut (Virginia Tech, 2014-10-15)Rupture of the anterior cruciate ligament (ACL) is one of the most common ligamentous injuries of the knee. Post rupture, the ACL does not heal on itself due to poor vasculature and hence surgical intervention is required to treat the ACL. Current surgical management of ACL rupture consists of reconstruction with autografts or allografts. However, the limitations associated with these grafts have prompted interest in tissue engineered solutions that combine cells, scaffolds and stimuli to facilitate ACL regeneration. This thesis describes a ligament tissue engineering strategy that involves incorporating biomolecules within fibers-based electrospun meshes which mimics the extra-cellular matrix microarchitecture of ligament. However, challenges exist with incorporation of biomolecules. Therefore, the goal of this research project was to develop two techniques to incorporate biomolecules within electrospun meshes: (1) co-axially electrospinning fibers that support surface-grafting of biomolecules, and (2) co-axially electrospinning fibers decorated with biomolecule-loaded microspheres. In the first approach, chitosan was co-axially electrospun on the shell side of poly caprolactone (PCL) and arginine-glycine-aspartate (RGD) was attached to the electrospun meshes. Bone marrow stromal cells (BMSCs) attached, spread and proliferated on these meshes. In the second approach, fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA) loaded chitosan-alginate (CS-AL) microspheres were fabricated. The effects of cation to alginate ratio, type of alginate and concentration of CaCl2 on microsphere size, FITC-BSA loading and release were systematically evaluated. The CS-AL microspheres were then incorporated into the sheath phase of co-axially electrospun meshes to achieve microsphere-decorated fiber composite meshes. The results from these model study suggest that both approaches are tractable for incorporating biomolecules within fibers-based electrospun meshes. Both these approaches provide platform for future studies that can focus on ligament-relevant biomolecules such as FGF-2 and GDF-5.
- Ammonium Bisphosphonate Polymeric Magnetic Nanocomplexes for Platinum Anticancer Drug Delivery and Imaging with Potential Hyperthermia and Temperature-Dependent Drug ReleaseZhang, Rui; Fellows, Benjamin; Pothayee, Nikorn; Hu, Nan; Pothayee, Nipon; Jo, Ami; Bohórquez, Ana C.; Rinaldi, Carlos; Mefford, Olin Thompson; Davis, Richey M.; Riffle, Judy S. (Hindawi, 2018-08-05)Novel magnetite-ammonium bisphosphonate graft ionic copolymer nanocomplexes (MGICs) have been developed for potential drug delivery, magnetic resonance imaging, and hyperthermia applications. The complexes displayed relatively uniform sizes with narrow size distributions upon self-assembly in aqueous media, and their sizes were stable under simulated physiological conditions for at least 7 days. The anticancer drugs, cisplatin and carboplatin, were loaded into the complexes, and sustained release of both drugs was observed. The transverse NMR relaxivities (s) of the complexes were 244 s−1 (mM Fe)−1 which is fast compared to either the commercial T2-weighted MRI agent Feridex IV® or our previously reported magnetite-block ionomer complexes. Phantom MRI images of the complexes demonstrated excellent negative contrast effects of such complexes. Thus, the bisphosphonate-bearing MGICs could be promising candidates for dual drug delivery and magnetic resonance imaging. Moreover, the bisphosphonate MGICs generate heat under an alternating magnetic field of 30 kA·m−1 at 206 kHz. The temperature of the MGIC dispersion in deionized water increased from 37 to 41°C after exposure to the magnetic field for 10 minutes, corresponding to a specific absorption rate of 77.0 W·g−1. This suggests their potential as hyperthermia treatment agents as well as the possibility of temperature-dependent drug release, making MGICs more versatile in potential drug delivery applications.
- Application of COSMO-SAC to Solid Solubility in Pure and Mixed Solvent Mixtures for Organic Pharmacological CompoundsMullins, Paul Eric (Virginia Tech, 2007-01-24)In this work, we present two open literature databases, the VT-2005 Sigma Profile Database and the VT-2006 Solute Sigma Profile Database, that contain sigma profiles for 1,645 unique compounds. A sigma profile is a molecular-specific distribution of the surface-charge density, which enables the application of solvation-thermodynamic models to predict vapor-liquid and solid-liquid equilibria, and other properties. The VT-2005 Sigma Profile Database generally focuses on solvents and small molecules, while the VT-2006 Solute Sigma Profile Database primarily consists of larger, pharmaceutical-related solutes. We design both of these databases for use with the conductor-like screening model−segment activity coefficient (COSMO-SAC), a liquid-phase activity-coefficient model. The databases contain the necessary information to perform binary and multicomponent VLE and SLE predictions. We offer detailed tutorials and procedures for use with our programs so the reader may also use their own research on our research group website (www.design.che.vt.edu). We validate the VT-2005 Sigma Profile Database by pure component vapor pressure predictions and validate the VT-2006 Solute Sigma Profile Database by solid solubility predictions in pure solvents compared with literature data from multiple sources. Using both databases, we also explore the application of COSMO-SAC to solubility predictions in mixed solvents. This work also studies the effects of conformational isomerism on VLE and SLE property prediction. Finally, we compare COSMO-SAC solubility predictions to solubility predictions by the Non-Random Two-Liquid, Segment Activity Coefficient (NRTL-SAC) model. We find UNIFAC is a more accurate method for predicting VLE behavior than the COSMO-SAC model for many of the systems studied, and that COSMO-SAC predicts solute mole fraction in pure solvents with an average root-mean-squared error (log10(xsol)) of 0.74, excluding outliers, which is greater than the RMS error value of 0.43 using the NRTL-SAC model.
- Application of Extended DLVO Theory: Modeling of Flotation and Hydrophobicity of DodecaneMao, Laiqun (Virginia Tech, 1998-05-23)The extended DLVO theory was used to develop a flotation model by considering both hydrodynamic and surface forces involved in the process. A stream function was used to estimate the kinetic energies for thinning the water films between bubbles and particles, which were compared with the energy barriers, created by surface forces, to determine the probability of adhesion. A general expression for the probability of detachment was derived from similar mechanism for chemical reaction, and the kinetic energy for detachment was estimated with French and Wilson's model. The hydrophobic force parameter (K132) calculated from the rate constants of single bubble flotation tests showed that, K132 for bubble-particle interaction were close to the geometric means of K131 for particle-particle interactions and K232 for bubble-bubble interaction, indicating that the combining rules developed for dispersion forces may be useful for hydrophobic forces. The model was used to predict flotation results as functions of several important parameters such as contact angle, double-layer potentials, particle size, bubble size, etc. The predictions were consistent with experience, and could be explained in view of the various subprocesses considered in the model development. Furthermore, the model suggested optimum conditions for achieving the maximum separation efficiency. The extended DLVO theory was also used to determine the hydrophobic force between two oil/solution interfaces from the equilibrium film thicknesses of dodecylammonium chloride (RNH3Cl) solutions obtained using Thin Film Balance (TFB) technique. The results showed that, the oil droplets were inherently hydrophobic, and the hydrophobic force played an important role in the stability of emulsions. This force decreased with increasing surfactant concentration, and also changed with pH and the addition of electrolyte. The interfacial area occupied by molecules indicated that, the dodecane molecules might present between two surfactant ions at interface, thus the hydrophobicity of oil/solution interface was less sensitive to the addition of the surfactant than that of air/solution interface. Thermodynamic analysis suggested that, there might exist a relationship between the interfacial hydrophobicity and the interfacial tension.
- Application of Fluid Flow for Functional Tissue Engineering of Bone Marrow Stromal CellsKreke, Michelle Renee (Virginia Tech, 2005-04-19)In the United States, nearly half a million bone graft operations are performed annually to repair defects arising from birth defects, trauma, and disease, making bone the second most transplanted tissue. Autogenous bone is the current gold standard for bone grafts; however it is in limited supply and results in a second injury at the donor site. A promising alternative is a tissue engineered bone graft composed of a biomaterial scaffold, pharmaceutics, and osteoprogenitor cells. One source of osteoprogenitor cells is bone marrow stroma, which can be obtained from the patient - minimizing the risk of an immune response - directed in vitro to proliferate, and differentiate into a bone-like tissue. To date, tissue engineered bone grafts have not been clinically effective; thus, strategies must be developed to improve efficacy. I hypothesize that to facilitate tissue healing in a manner similar to autogenous bone tissue engineering bone must possess a mineralized collagen matrix to support tissue integration, and angiogenic factors to stimulate vascular infiltration, and osteogenic factors to direct normal bone remodeling. I propose that these factors can be synthesized by osteoprogenitor cells in vitro when cultured under the appropriate conditions. Previous work has demonstrated that perfusion culture of osteoprogenitor cells within 3D scaffolds stimulates phenotypic markers of osteoblastic differentiation, but those studies did not determine whether the effects were a consequence of shear stress or increased nutrient availability. Consequently, this work has involved studies in a planar geometry, where nutrient effects are negligible. Three studies that characterize the effect of fluid flow on osteoblastic differentiation of osteoprogenitor cells are presented here. The objective of the first study was to determine the effect of shear stress magnitude on cell density and osteocalcin deposition. In this study, radial flow chambers were used to generate a spatially dependent range of shear stresses (0.36 to 2.7 dynes/cm2) across single substrates, and immunofluorescent techniques were used to assay cell phenotype as a function of shear stress. The objective of the second study was to determine the effect of the duration of fluid flow on cell density and phenotypic markers of differentiation. Here, parallel plate flow chambers were used to generate a single shear stress at the cell surface, and entire cell layers were assayed for expression of osteoblastic genes. The objective of the third study was to compare continuous and intermittent fluid flow strategies. In this study, a microprocessor-controlled actuator was added to the flow loop to periodically halt flow, and markers of mechanosensation and osteoblastic differentiation were measured. These studies demonstrated that shear stresses of 0.36 to 2.7 dynes/cm2 stimulate late phenotypic markers of osteoblastic differentiation but not cell proliferation. In addition, this osteogenic effect is sensitive to duration of fluid flow but insensitive to the magnitude of shear stress. Further, intermittent fluid flow enhances cell retention, biochemical markers of mechanotransduction, and synthesis of the angiogenic factor vascular endothelial growth factor (VEGF). Thus, these studies suggest that intermittent fluid flow may be an attractive component of a biodynamic bioreactor for in vitro manufacture of clinically effective tissue engineered bone grafts. Future studies will further investigate intermittent fluid flow strategies and three-dimensional studies with scaffolds suitable for bone tissue engineering.
- Applications of Layer-by-Layer Films in Electrochromic Devices and Bending ActuatorsJain, Vaibhav (Virginia Tech, 2009-09-02)This thesis presents work done to improve the switching speed and contrast performance of electrochromic devices. Layer-by-Layer (LbL) assembly was used to deposit thin electrochromic films of materials ranging from organic, inorganic, conducting polymers, etc. The focus was on developing new materials with high contrast and long lifecycles. A detailed switching-speed study of solid-state EC devices of already-developed (PEDOT (Poly(3,4-ethylenedioxythiophene)), polyviologen, inorganic) materials and some new materials (Prodot-Sultone) was performed. Work was done to achieve the optimum thickness and number of bilayers in LbL films resulting in high-contrast and fast switching. Device sizes were varied for comparison of the performance of the lab-made prototype device with the commercially available "small pixel" size displays. Symmetrical EC devices were fabricated and tested whenever conducting polymers are used as an EC material. This symmetrical configuration utilizes conducting polymers as an electroactive layer on each of two ITO-coated substrates; potential is applied to the two layers of similar conducting polymers and the device changes color from one redox state to another. This method, along with LbL film assembly, are the main factors in the improvement of switching speed results over already-published work in the literature. PEDOT results show that EC devices fabricated by LbL assembly with a switching speed of less than 30 ms make EC flat-panel displays possible by adjusting film thickness, device size, and type of material. The high contrast value (84%) for RuP suggests that its LbL films can be used for low-power consumption displays where contrast, not fastest switching, is the prime importance. In addition to the electrochromic work, this thesis also includes a section on the application of LbL assembly in fabricating electromechanical bending actuators. For bending actuators based on ionic polymer metal composites (IPMCs), a new class of conductive composite network (CNC) electrode was investigated, based on LbL self-assembled multilayers of conductive gold (Au) nanoparticles. The CNC of an electromechanical actuator fabricated with 100 bilayers of polyallylamine hydrochloride (PAH)/Au NPs exhibits high strain value of 6.8% with an actuation speed of 0.18 seconds for a 26 µm thick IPMC with 0.4 µm thick LbL CNCs under 4 volts.
- Benign Processing of High Performance Polymeric Foams of Poly(arylene ether sulfone)VanHouten, Desmond J. (Virginia Tech, 2008-12-02)This work is concerned with the production of high performance polymer foams via a benign foaming process. The first goal of this project was to develop a process and the conditions necessary to produce a low density (>80% density reduction) foam from poly(arylene ether sulfone) (PAES). Water and supercritical carbon dioxide (scCO2) were used as the blowing agents in a one-step batch foaming process. Both water and scCO2 plasticize the PAES, allowing for precise control on both the foam morphology and the foam density. To optimize the foaming conditions, both thermogravimetric analysis and differential scanning calorimetery (DSC) were used to determine the solubility and the reduced glass transition temperature (Tg) due to plasticization of the polymer. It was determined that 2 hours was sufficient time to saturate the PAES with water and scCO2 when subjected to a temperature of 220 oC and 10.3 MPa of pressure. Under these conditions, a combination of 7.5% of water and scCO2 were able to diffuse into the PAES specimen, correlating to ~60 oC reduction in the Tg of the PAES. The combination of water and scCO2 produced foam with up to an 80% reduction in density. The compressive properties, tensile modulus, and impact strength of the foam were measured. The relative compressive properties were slightly lower than the commercially available structural foam made of poly(methacrylimide). The second objective of the dissertation was to enhance the compressive properties of the PAES foam, without concern for the foam density. Foam was produced over a range of density, by controlling the cell size, in order to optimize the compressive properties. Carbon nanofibers (CNFs) were also added to the PAES matrix prior to foaming to both induce heterogeneous nucleation, which leads to smaller cell size, and to reinforce the cell walls. Dynamic mechanical thermal analysis (DMTA), on saturated CNF-PAES, was used to determine the reduced Tg due to plasticization and establish the temperature for pressure release during foaming. DMTA proved to be more effective than DSC in establishing quantitative results on the reduction in the Tg. The CNF-PAES foam produced had compressive properties up to 1.5 times the compressive properties of the PAES foam.
- Biologically Controlled Mineralization and Demineralization of Amorphous SilicaWallace, Adam F. (Virginia Tech, 2008-04-24)Living systems possess seemingly bottomless complexity. Attempts to parse the details of one cellular process from all other concurrent processes are challenging, if not daunting undertakings. The apparent depth of this problem, as it pertains to biomineralization, is related to the small number of existing studies focused on the development of a mechanism-based understanding of intracellular mineralization processes. Molecular biologists and geneticists have only begun to turn their attention towards identification and characterization of molecules involved in regulating and controlling biomineral formation. With this new knowledge, a number of new and exciting research opportunities are currently awaiting development upon a barren landscape. Silica biomineralization is one of these emerging frontiers. As new information about the chemical and structural nature of the macromolecules involved in biosilicification is revealed, the means these species employ to control the temporal and spatial onset of silica deposition in vivo become available for exploration. The first chapter of this dissertation outlines those aspects of silicate metabolism that are directly relevant to the controlled biomineralization of silica in eukaryotic organisms and identifies pervasive and unanswered questions surrounding biosilica formation. Particular attention is paid to the diatoms, which are the most abundant, and extensively investigated silica-mineralizing organisms in modern seas. The extent, and mechanism through which specific organic moieties work individually or in concert to direct mineral formation at biological interfaces is a central concern of modern biomineralization research. Chapter two addresses this forefront issue for silica mineralizing systems, and reports the results of an experimental investigation designed to measure the effects of individual surface-bound organic functional groups on the rate of surface-directed silica nucleation. Chapter three discusses an additional aspect of this research aimed at investigating the reactivity of nanoparticulate biogenic silica produced by marine phytoplankton and terrestrial plants in natural environments. Density Functional Theory and ab initio molecular orbital calculations are employed to explore potential mechanisms underlying the catalytic activity of divalent metal cations during the hydrolysis of Si – O bonded networks.
- Biomanufacturing of Bacteria-Mediated Drug Delivery Systems and Investigation of Their Interaction with the Tumor MicroenvironmentZhan, Ying (Virginia Tech, 2024-05-14)The limited transport of conventional chemotherapy within the tumor microenvironment (TME) is due to irregular vascularization, increased tumor interstitial pressure, and a dense extracellular matrix (ECM). The lack of selectivity of anticancer drugs often leads to systemic toxicity and damage to healthy tissues. Bacteria-based cancer therapy (BBCT) is a promising alternative, as tumor-targeting bacteria have been shown to preferentially colonize primary and metastatic tumors and induce anti-tumor effects. In this dissertation, we focus on several aspects of bacteria-nanoparticle conjugates, wherein BBCT is synergistically combined with nanomedicine to augment the efficacy of both treatment modalities. We explore biofabrication of our bacteria-nanoparticle conjugates called NanoBEADS (Nanoscale Bacteria Enabled Autonomous Drug Delivery Systems) and their interaction with the TME. Specifically, (1) we investigate the effects of two bacteria-NP conjugation chemistry and assembly process parameters of mixing method, volume, and duration, on NP attachment density and repeatability. We evaluate the influence of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS. (2) We investigate the effect of dense stroma and ECM production on the intratumoral penetration of bacteria with a mathematical model of bacterial intratumoral transport and growth. (3) We develop a microfluidic device with multicellular tumor spheroids to study the transport of tumor-targeting bacteria and support real-time imaging and long-term experiments. (4) We develop a new type of bacteria-based bio-hybrid drug delivery system using engineered cell surface display for enhancing the attachment of nanoparticles.
- Bioresorbable Electrospun Tissue Scaffolds of Poly(ethylene glycol-b-lactide) Copolymers for Bone Tissue EngineeringBadami, Anand Shreyans (Virginia Tech, 2004-10-01)Poly(α-hydroxy esters) are a class of biocompatible resorbable polyesters including poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) that are FDA-approved for clinical use. Preliminary tissue culture studies have demonstrated that these poly(α-hydroxy esters) support bone tissue development both in vitro and in vivo, but biocompatibility issues still exist. Tissue scaffolds fabricated from these materials by current methods have biocompatibility limitations because they are chemically and topographically inert to cells. The chemical composition of these scaffolds does not influence cell behavior (i.e. proliferation, differentiation) and their surface topography is on a scale length larger than a cell, which is too large to affect cell adhesion or orientation. It is hypothesized that poly(α-hydroxy ester) tissue scaffolds can be made more bioactive by (1) incorporating poly(ethylene glycol) (PEG) into the polymer interface to promote osteoblastic differentiation and (2) controlling topography to direct cell behavior. The novel processing technique of electrospinning allows the fabrication of nanofiber scaffolds with topographical features the size of focal adhesion contacts capable of influencing cell behavior. Thus, the overall objective of this research project is to characterize electrospun PEG-PLA diblock copolymers as substrates for bone tissue engineering. To accomplish this, PEG-PLLA and PEG-PDLLA diblock copolymers were synthesized with target molecular weights of 42,000 g/mol (PEG:2000, PLLA or PDLLA:40,000). Next, these two polymers and commercially available PLLA and PDLLA were electrospun to form scaffolds with fibers of diameters 0.14 to 2.1 μm. Finally, cell culture studies were performed to characterize cell morphology, proliferation, and osteoblastic differentiation. Results indicate electrospun fiber scaffolds limit cell spreading and persist in cell culture for two weeks. Analysis of cells cultured over 14 days revealed that there were no differences in cell density between polymers with and without PEG. Cell density increased with fiber diameter, indicating that fiber diameter affects cell adhesion and proliferation and suggesting that cells may migrate into scaffolds with large diameter fibers. In contrast to cell density, ALP activity, an indicator of osteoblastic differentiation, was unaffected by fiber diameter.
- Blends of Biodegradable Thermoplastics With Lignin EstersGhosh, Indrajit (Virginia Tech, 1998-04-22)Thermoplastic blends of several biodegradable polymers with lignin (L) and lignin esters were prepared by solvent casting and melt processing. Among the biodegradable thermoplastics were cellulose acetate butyrate (CAB), poly-hydroxybutyrate (PHB), poly-hydroxybutyrate-co-valerate (PHBV), and a starch-caprolactone blend (SCL). Lignin esters included acetate (LA), butyrate (LB), hexanoate (LH), and laurate (LL). Blend characteristics were analyzed in terms of thermal and mechanical properties. The results indicate widely different levels of interaction between two polymer constituents. Melt blended samples of CAB/LA and CAB/LB were compatible on a 15-30 nm scale when probed by dynamic mechanical thermal analysis, and the glass transition temperatures of the blends followed Fox equation, whereas those of CAB/LH and CAB/LL showed distinct broad transitions on the same scale. Melt blending produced well dispersed phases whereas large phase separation evolved out of solvent castings. Crystallinity and melting points of PHB and PHBV were affected by the incorporation of lignin component, revealing some interaction between the blend constituents. Blends of SCL with L and LB revealed significant effect on crystallinity and melting temperatures of poly-caprolactone component, revealing polymer-polymer interaction between SCL and lignin components. An increased degree of crystallinity was observed in the case of higher-Tg L compared to lower Tg LB. Improvememt in modulus (and in some cases strength also) was observed in almost all blends types due to the glassy reinforcing behavior of lignin.
- Block and Graft Copolymers Containing Carboxylate or Phosphonate AnionsHu, Nan (Virginia Tech, 2014-11-06)This dissertation focuses on synthesis and characterization of graft and block copolymers containing carboxylate or phosphonate anions that are potential candidates for biomedical applications such as drug delivery and dental adhesives. Ammonium bisdiethylphosphonate (meth)acrylate and acrylamide phosphonate monomers were synthesized based on aza-Michael addition reactions. Free radical copolymerizations of these monomers with an acrylate-functional poly(ethylene oxide) (PEO) macromonomer produced graft copolymers. Quantitative deprotection of the alkylphosphonate groups afforded graft copolymers with zwitterionic ammonium bisphosphonate or anionic phosphonate backbones and PEO grafts. The zwitterionic copolymers spontaneously assembled into aggregates in aqueous media. The anionic copolymers formed aggregates in DMF and DMSO, while only small amounts of aggregates were present in copolymer/methanol or copolymer/water solutions. Binding capabilities of the acrylamide phosphonic acids were investigated through interactions with hydroxyapatite. Previously our group has prepared poly(ethylene oxide)-b-poly(acrylic acid) (PEO-b-PAA) copolymers and used these polymers as carriers for both MRI imaging agents and cationic drugs. To enhance the capabilities of those carriers in tracking and crosslinking, we have designed, synthesized and characterized amine functionalized PEO-b-PAA copolymers. First, heterobifunctional poly(ethylene oxide) (PEO) with three different molecular weights were synthesized. Modification on one of these afforded a PEO macroinitiator with a bromide on one end and a protected amine on the other end. ATRP polymerization of tert-butyl acrylate (tBuA) in the presence of this initiator and a copper (I) bromide (CuBr) catalyst yielded a diblock copolymer. The copolymer was deprotected by reaction with trifluoroacetic acid (TFA) and formed an amine terminated H2N-PEO-b-PAA. Recently our group has utilized the novel ammonium bisdiethylphosphonate (meth)acrylate and acrylamide phosphonate copolymers to incorporate Carboplatin. The resulting complexes exhibited excellent anticancer activity against MCF-7 breast cancer cells which might be related to ligand exchange of the dicarboxylate group of Carboplatin with the phosphonic acid moieties in the copolymer. Hence, complexation of small-molecule phosphonic acids with Carboplatin was investigated. Three compounds, vinylphosphonic acid, 3-hydroxypropyl ammonium bisphosphonic acid and 2-hydroxyethyl ammonium phosphonic acid were complexed with Carboplatin under acidic and neutral conditions. Covalent bonding of these acids to carboplatin was only observed under acidic pH. The covalently bonded percentage was 17%, 37% and 34%, respectively. More in-depth investigation was of great importance to further understand this complexation behavior.
- Breakup and coalescence in turbulent two-phase flowsHunt, William E. (Virginia Tech, 1995-07-05)Many engineering processes involve a gas and a liquid or two immiscible liquids in turbulent flow. The turbulent flows present in two-phase systems will cause the bubbles or drops of a dispersion to undergo breakup and coalescence, and the resulting changes in the dispersion may significantly affect the engineering process under consideration. For this reason, many researchers have studied breakup and coalescence in turbulent two phase flows. Models that can be used to simulate changes in a dispersion over time have been proposed, but these models contain constants that change with experimental conditions and empirical equations that can only be considered valid for certain experimental setups. The goal of this study was to develop general models that could be used to predict changes in bubble or drop size distributions over time for turbulent flows in agitated vessels and pipes. Computer programs were written to reproduce the results of three agitated vessel studies. These programs used existing population balance models to approximate the changes in a dispersion over time measured in previous experiments. A new model for breakup in agitated vessels was then developed and verified with existing experimental data. A new model for coalescence in agitated vessels was also developed and verified with existing experimental data. Both of these models are based on theory and are more readily extendible than previous breakup and coalescence models. The work for agitated vessels was then extended to turbulent two-phase pipe flow. Since there was only a limited amount of experimental data available for breakup and coalescence in pipes, the model for turbulent pipe flow could not be verified.
- Catalytic Transformation of Greenhouse Gases in a Membrane ReactorPrabhu, Anil K. (Virginia Tech, 2003-03-13)Supported Ni and Rh catalysts were developed for the reforming of two greenhouse gases, methane and carbon dioxide to syngas (a mixture of hydrogen and carbon monoxide). This is an endothermic, equilibrium limited reaction. To overcome the thermodynamic limitations, a commercially available porous membrane (Vycor glass) was used in a combined reactor-separator configuration. This was to selectively remove one or more of the products from the reaction chamber, and consequently shift the equilibrium to the right. However, the separation mechanism in this membrane involved Knudsen diffusion, which provided only partial separations. Consequently, there was some transport of reactants across the membrane and this led to only marginal improvements in performance. To overcome this limitation, a new membrane was developed by modifying the Vycor substrate by the chemical vapor deposition of a silica precursor. This new membrane, termed Nanosil, provided high selectivity to hydrogen at permeabilities comparable to the support material. Application of this membrane in the combined reactor-separator unit provided higher conversions than that obtained using the Vycor membrane.
- Cell Migration on Opposing Rigidity Protein Gradients: Single Cell and Co-culture StudiesJain, Gaurav (Virginia Tech, 2014-10-31)Cell migration is a complex physiological process that is important from embryogenesis to senescence. In vivo, the migration of cells is guided by a complex combination of signals and cues. Directed migration is typically observed when one of these cues is presented to cells as a gradient. Several studies have been conducted into directed migration on gradients that are purely mechanical or chemical. Our goal was to investigate cellular migratory behavior when cells are presented with a choice and have to choose between increasing substrate rigidity or higher protein concentration. We chose to focus on this unique environment since it recapitulates several interfacial regions in vivo. We have designed novel hydrogels that exhibit dual and opposing chemical and mechanical profiles using photo-polymerization. Our studies demonstrate that durotaxis, a well-known phenomenon, can be reversed when cells sense a steep protein profile in the opposite direction. Fibroblasts were co-cultured with macrophages to obtain an understanding on how migration occurs when two different cell types are present in the same microenvironment. First, we investigated the migratory behavior of macrophages. These cell types exhibited a statistically significant preference to move towards the rigid/low collagen region of the interface. Interestingly, fibroblasts when co-cultured with macrophages, exhibited a preference for the low modulus-high collagen region of the interface. However, with the current sample size, these trends are statistically insignificant. On the contrary, the presence of fibroblasts in the cellular microenvironment did not result in the reversal of durotaxis exhibited by macrophages. Macrophages secreted significantly higher levels of secreted tumor necrosis factor (TNF-alpha) in mono-cultures in contrast to fibroblast-macrophage co-cultures. This trend could be an indication of macrophage plasticity between mono- and co-cultures. In summary, we have designed dual and opposing rigidity-protein gradients on a hydrogel substrate that can provide new insights into cellular locomotion. These results can be used to design biomimetic interfaces, biomaterial implants and for tissue engineering applications.
- Cellulose Esters and Cellulose Ether Esters for Oral Drug Delivery SystemsArca, Hale Cigdem (Virginia Tech, 2016-11-01)Amorphous solid dispersion (ASD) is a popular method to increase drug solubility and consequently poor drug bioavailability. Cellulose ω-carboxyesters were designed and synthesized specifically for ASD preparations in Edgar lab that can meet the ASD expectations such as high Tg, recrystallization prevention and pH-triggered release due to the free -COOH groups. Rifampicin (Rif), Ritonavir (Rit), Efavirenz (Efa), Etravirine (Etra) and Quercetin (Que) cellulose ester ASDs were investigated in order to increase drug solubility, prevent release at low pH and controlled release of the drug at small intestine pH that can improve drug bioavailability, decrease needed drug content and medication price to make it affordable in third world countries, and extent pill efficiency period to improve patient quality of life and adherence to the treatment schedule. The studies were compared with cellulose based commercial polymers to prove the impact of the investigation and potential for the application. Furthermore, the in vitro results obtained were further supported by in vivo studies to prove the significant increase in bioavailability and show the extended release. The need of new cellulose derivatives for ASD applications extended the research area, the design and synthesis of a new class of polymers, alkyl cellulose ω-carboxyesters for ASD formulations investigated and the efficiency of the polymers were summarized to show that they have the anticipated properties. The polymers were synthesized by the reaction of commercial cellulose alkyl ethers with benzyl ester protected, monofunctional hydrocarbon chain acid chlorides, followed by removal of protecting group using palladium hydroxide catalyzed hydrogenolysis to form the alkyl cellulose wcarboxyalkanoate. Having been tested for ASD preparation, it was proven that the polymers were efficient in maintaining the drug in amorphous solid state, release the drug at neutral pH and prevent the recrystallization for hours, as predicted.