The interaction of materials with biological systems is of critical importance to a vast number of applications from medical implants, tissue engineering scaffolds, blood-contacting devices, cell-culture products, as well as many other products in industries as diverse as agriculture. This thesis describes a method for the modification of biomaterial surfaces and the generation of tissue engineering scaffolds that utilises the self assembly of poly (styrene)-block-poly (ethylene oxide) (PS-PEO) block copolymers. Block copolymers consist of alternating segments of two or more chemically distinct polymers. The salient feature of these materials is their ability to self organise into a wide range of micro-phase separated structures generating patterned surfaces that have domain sizes in the order of 10-100nm. Further, it is also possible to specifically functionalise only one segment of the block copolymer, providing a means to precisely locate specific biological signals within the 10-100nm domains of a nano-patterned surface, formed via the programmed micro-phase separation of the block copolymer system. The density and spatial location of signalling molecules can be controlled by altering several variables, such as block length, block asymmetry, as well as processing parameters, providing the potential to authentically emulate the cellular micro to nano-environment and thus greatly improving on existing biomaterial and tissue engineering technologies. This thesis achieved several aims as outlined below; Developed methods to control the self-assembly of PS-PEO block copolymers and generate nano-patterned surfaces and scaffolds with utility for biomaterials applications. PS-PEO diblock copolymers were blended with polystyrene (PS) homopolymer and spin cast, resulting in the rapid self-assembly of vertically oriented PEO cylinders in a matrix of PS. Due to the kinetically constrained phase-separation of the system, increasing addition of homopolymer is shown to reduce the diameter of the PEO domains. This outcome provides a simple method that requires the adjustment of a single variable to tune the size of vertically oriented PEO domains between 10-100nm. Polymeric scaffolds for tissue engineering were manufactured via a method that combines macro-scale temperature induced phase separation with micro-phase separation of block copolymers. The phase behaviour of these polymer-solvent systems is described, and potential mechanisms leading to this spectacular structure formation are presented. The result is highly porous scaffolds with surfaces comprised of nano-scale self-assembled block copolymer domains, representing a significant advance in currently available technologies. Characterised the properties of these unique nano-structured materials as well as their interaction with proteinaceous fluids and cells. Nano-patterned PS-PEO self-assembled surfaces showed a significant reduction in protein adsorption compared to control PS surfaces. The adhesion of NIH 3T3 fibroblast cells was shown to be significantly affected by the surface coverage of PEO nano-domains formed by copolymer self-assembly. These nano-islands, when presented at high number density (almost 1000 domains per square micron), were shown to completely prevent cellular attachment, even though small amounts of protein were able to bind to the surface. In order to understand the mechanism by which these surfaces resisted protein and cellular adsorption we utilised neutron reflection to study their solvation and swelling properties. The results indicate that the PEO domains are highly solvated in water; however, the PEO chains do not extend into the solvent but remain in their isolated domains. The data supports growing evidence that the key mechanism by which PEO prevents protein adsorption is the blocking of protein adsorption sites. Control the nano-scale presentation of cellular adhesion and other biological molecules via the self-assembly of functionalised PS-PEO block copolymers Precise control over the nano-scale presentation of adhesion molecules and other biological factors represents a new frontier for biomaterials science. Recently, the control of integrin spacing and cellular shape has been shown to affect fundamental biological processes, including differentiation and apoptosis. We present the self-assembly of maleimide functionalised PS-PEO copolymers as a simple, yet highly precise method for controlling the position of cellular adhesion molecules. By controlling the phase separation of the functional PS-PEO block copolymer we alter the nano-scale (on PEO islands of 8-14 nm in size) presentation of the adhesion peptide, GRGDS, decreasing lateral spacing from 62 nm to 44 nm and increasing the number density from ~ 450 to ~ 900 islands per um2. The results indicate that the spreading of NIH-3T3 fibroblasts increases as the spacing between islands of RGD binding peptides decreases. Further, the same functional PS-PEO surfaces were utilised to immobilise poly-histidine tagged proteins and ECM fragments. The technologies developed in this thesis aim to improve on several weaknesses of existing biomaterials, in particular, directing cellular behaviour on surfaces, and within tissue engineering scaffolds, but also, on the prevention of fouling of biomaterials via non-specific protein adsorption. The application of block copolymer self-assembly for biomaterial and tissue engineering systems described in this thesis has great potential as a platform technology for the investigation of fundamental cell-surface and protein-surface interactions as well as for use in existing and emerging biomedical applications.

En la actualidad el mercado carece de prendas elásticas para uso profesional puesto que los elastanos habitualmente utilizados son inestables frente a altas temperaturas y químicos agresivos, e.g. termofijado, mantenimiento de indumentaria industrial etc. Recientemente se han venido utilizado filamentos olefínicos obtenidos a partir de copolímeros al azar de etileno-octeno (Dow XLA fibers producidos por The Dow Chemical Company). Aunque más resistentes a las temperaturas debido a la reticulación, su bajo punto de fusión, alrededor de 50ºC, limita el comportamiento elástico en tejidos pesados y tupidos para indumentaria profesional. La investigación tiene por objeto la obtención de monofilamentos elásticos a partir copolímeros de bloque de etileno-octeno (cuyo punto de fusión es más elevado) y con éstos, tejidos para indumentaria profesional que ofrezcan mayor fuerza de encogimiento a las temperaturas típicas de los pre-tratamientos, tintura y acabado (50ºC-120ºC). El objetivo es hacer que los tejidos encojan más durante las operaciones en húmedo bajo temperatura para mejorar así su elasticidad y aumentar el peso en comparación con los tejidos actuales manufacturados con los convencionales copolímeros homogéneos de etileno-octeno reticulados Los tejidos deberán garantizar las siguientes propiedades durante todo su ciclo de vida: estabilidad dimensional, relación elasticidad-crecimiento mejorado, resistencia química, resistencia térmica, durabilidad ante los lavados industriales y un mejor confort termofisiológico y sensorial. / Due to the lack of stability of elastane based materials against high temperatures and harsh chemicals, e.g. thermofixation and professional wear maintenance, elastic garments with elastane content are not yet fully commercial products. The Dow Chemical Company has recently commercialized a random ethylene-octene copolymer based fiber named Dow XLA fiber. Despite its higher temperature resistance as one of the crosslinking effects, its very low melting point, around 50ºC, establishes some limitations in elasticity such in heavy weight and high densely woven fabric cases typically found in professional wear applications. The target for the investigation is to produce block ethyleneoctene copolymer based filaments in which the melting point is supposed to be higher than in random copolymer materials. Different workwear fabrics will be manufactured with yarns containing such elastic filaments. It is supposed these fabrics to show high shrinkage forces even at dyeing and finishing temperatures, (50ºC-120ºC). The goal is to produce fabrics with superior shrinkage performance in order to achieve an excellent elastic power and the final desired fabric weight. Properties such as dimensional stability, stretch and growth ratio, temperature and chemical resistance and durability against industrial laundering should not be affected by the passage of the time. To validate this point these properties will be measured in the fabrics off loom and after the garment cycle life. These fabrics are also supposed to show better thermophysiological and sensorial properties than random copolymer fiber based textiles

Estimating reactivity ratios in multicomponent polymerizations is becoming increasingly important. At the same time, using cumulative models is becoming imperative, as some multicomponent systems are inherently so fast that instantaneous "approximate" models can not be used. In the first part of the thesis, triad fractions (sequence length characteristics) are employed in a multiresponse scenario, investigating different error structures and levels. A comparison is given between instantaneous triad fraction models and instantaneous composition model, which represent the current state-of-the-art. In the second part of the thesis, extensions are discussed with cumulative composition and triad fraction models over the whole conversion range, thus relating the problem of reactivity ratio estimation to the optimal design of experiments (i. e. optimal sampling) over polymerization time and conversion. The performance of cumulative multiresponse models is superior to that of their instantaneous counterparts, which can be explained from an information content point of view. As a side-project, the existence of azeotropic points is investigated in terpolymer (Alfrey-Goldfinger equation) and tetrapolymer (Walling-Briggs equation) systems.

Estimating reactivity ratios in multicomponent polymerizations is becoming increasingly important. At the same time, using cumulative models is becoming imperative, as some multicomponent systems are inherently so fast that instantaneous "approximate" models can not be used. In the first part of the thesis, triad fractions (sequence length characteristics) are employed in a multiresponse scenario, investigating different error structures and levels. A comparison is given between instantaneous triad fraction models and instantaneous composition model, which represent the current state-of-the-art. In the second part of the thesis, extensions are discussed with cumulative composition and triad fraction models over the whole conversion range, thus relating the problem of reactivity ratio estimation to the optimal design of experiments (i. e. optimal sampling) over polymerization time and conversion. The performance of cumulative multiresponse models is superior to that of their instantaneous counterparts, which can be explained from an information content point of view. As a side-project, the existence of azeotropic points is investigated in terpolymer (Alfrey-Goldfinger equation) and tetrapolymer (Walling-Briggs equation) systems.

Electrochemical polymerization of pyrrole functionalized polystyrene (PStPy) with pyrrole was carried out in water-sodium dodecyl sulfate solvent-electrolyte couple. Characterization of the resulting copolymer was performed via Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and four probe conductivity measurements. Glucose oxidase and polyphenol oxidase enzymes were immobilized in polypyrrole (PPy) and conducting copolymer of pyrrole functionalized polystyrene with pyrrole (P(PStPy-co-Py). Resulting enzyme electrodes were characterized by kinetic parameters / Vmax and Km. Behavior of enzyme electrodes upon temperature and pH changes were investigated. Glucose oxidase electrode was used for the determination of glucose in orange juice and polyphenol oxidase electrode was used for the determination of polyphenolic compounds in red wine.

Interfacial features of polymers are a complex, fascinating topic, and industrially very important. There is clearly a need to understand interactions between polymer layers as they can be used for controlling surface properties, colloidal stability and lubrication. The aim of my Ph.D study was to investigate fundamental phenomena of polymers at interfaces, covering adsorption, interactions between polymer layers and surfactants, surface forces and friction between adsorbed layers. A branched brush layer with high water content was formed on silica surfaces by a diblock copolymer, (METAC)m-b-(PEO45MEMA)n, via physisorption. The adsorption properties were determined using several complementary methods. Interactions between pre-adsorbed branched brush layers and the anionic surfactant SDS were investigated as well. Surface forces and friction between polymer layers in aqueous media were investigated by employing the Atomic Force Microscopy (AFM) colloidal probe technique. Friction forces between the surfaces coated by (METAC)m-b-(PEO45MEMA)n in water are characterized by a low friction coefficient. Further, the layers remain intact under high load and shear, and no destruction of the layer was noted even under the highest pressure employed, about 50 MPa. Interactions between polymer layers formed by a temperature responsive diblock copolymer, PIPOZ60-b-PAMPTMA17 (phase transition temperature of 46.1 °C), was investigated in the temperature interval 25-50 °C by using the AFM colloidal probe technique. Friction between the layers increases with increasing temperature (25-45 °C), while at 50 °C friction was found to be slightly lower than that at 45 °C. We suggest that this is due to decreased energy dissipation caused by PIPOZ chains crystallizing in water above the phase transition temperature. The structure of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers was determined by X-ray reflectometry. Surface forces and friction between DPPC bilayer-coated silica surfaces were measured utilizing the AFM colloidal probe technique. Our study showed that DPPC bilayers are able to provide low friction forces both in the gel (below ≈ 41°C) and in the liquid crystalline state (above ≈ 41°C). However, the load bearing capacity is lower in the gel state. This is attributed to a higher rigidity and lower self-healing capacity of the DPPC bilayer in the gel state. Friction forces in single asperity contact acting between a micro-patterned silicon surface and an AFM tip was measured in air. We found that both nanoscale surface heterogeneities and the µm-sized depressions affect friction forces, and considerable reproducible variations were found along a particular scan line. Nevertheless, Amontons’ first rule described average friction forces reasonably well. Amontons’ third rule and Euler’s rule were found to be less applicable to our system. / <p>QC 20141209</p>

No description available.

Recent advancements in pharmaceutical technology based on principles of nanotechnology, polymer chemistry, and biomedical engineering have resulted in the creation of novel drug delivery systems with the potential to revolutionize current strategies in cancer chemotherapy. In oncology, realization of significant improvements in therapeutic efficacy requires minimization of drug exposure to healthy tissues and concentration of the drug within the tumor. As such, encapsulation of chemotherapeutic agents inside nanoparticles capable of enhancing tumor-targeted drug delivery is a particularly promising innovation. Yet, initial investigations into the intratumoral fate of nanomedicines have suggested that they may be heterogeneously distributed and achieve limited access to cancer cells located distant from the tumor vasculature. As such, uncovering the determinants of nanoparticle transport at the intratumoral level is critical to the development of optimized delivery vehicles capable of fully exploiting the therapeutic potential of nanomedicines. In this work, the chemotherapeutic agent, docetaxel (DTX), was incorporated into nano-sized, biocompatible PEG-b-PCL block copolymer micelles (BCMs). Encapsulation of DTX in micelles via chemical conjugation or physical entrapment resulted in a dramatic increase in drug solubility and customizable drug release rate. The use of multicellular tumor spheroids (MCTS) was established as a viable platform for assessing the efficacy and tumor tissue penetration of nanomedicines in vitro. A series of complementary assays was validated for analysis of DTX-loaded micelle (BCM+DTX) toxicity in monolayer and spheroid cultures relative to Taxotere®. Cells cultured as spheroids were less responsive to treatment relative to monolayer cultures due to mechanisms of drug resistance associated with structural and microenvironmental properties of the 3-D tissue. Computational, image-based methodologies were used to assess the spatial and temporal penetration of BCMs in spheroids and corresponding human tumor xenografts. Using this approach, the tumor penetration of micelles was found to be nanoparticle-size-, tumor tissue type- and time- dependent. Furthermore, spheroids were found to be a valuable platform for the prediction of trends in nanoparticle transport in vivo. Overall, the results reported herein serve to demonstrate important determinants of nanoparticle intratumoral transport and to establish computational in vitro and in vivo methodologies for the rational design and optimization of nanomedicines.

Recent advancements in pharmaceutical technology based on principles of nanotechnology, polymer chemistry, and biomedical engineering have resulted in the creation of novel drug delivery systems with the potential to revolutionize current strategies in cancer chemotherapy. In oncology, realization of significant improvements in therapeutic efficacy requires minimization of drug exposure to healthy tissues and concentration of the drug within the tumor. As such, encapsulation of chemotherapeutic agents inside nanoparticles capable of enhancing tumor-targeted drug delivery is a particularly promising innovation. Yet, initial investigations into the intratumoral fate of nanomedicines have suggested that they may be heterogeneously distributed and achieve limited access to cancer cells located distant from the tumor vasculature. As such, uncovering the determinants of nanoparticle transport at the intratumoral level is critical to the development of optimized delivery vehicles capable of fully exploiting the therapeutic potential of nanomedicines. In this work, the chemotherapeutic agent, docetaxel (DTX), was incorporated into nano-sized, biocompatible PEG-b-PCL block copolymer micelles (BCMs). Encapsulation of DTX in micelles via chemical conjugation or physical entrapment resulted in a dramatic increase in drug solubility and customizable drug release rate. The use of multicellular tumor spheroids (MCTS) was established as a viable platform for assessing the efficacy and tumor tissue penetration of nanomedicines in vitro. A series of complementary assays was validated for analysis of DTX-loaded micelle (BCM+DTX) toxicity in monolayer and spheroid cultures relative to Taxotere®. Cells cultured as spheroids were less responsive to treatment relative to monolayer cultures due to mechanisms of drug resistance associated with structural and microenvironmental properties of the 3-D tissue. Computational, image-based methodologies were used to assess the spatial and temporal penetration of BCMs in spheroids and corresponding human tumor xenografts. Using this approach, the tumor penetration of micelles was found to be nanoparticle-size-, tumor tissue type- and time- dependent. Furthermore, spheroids were found to be a valuable platform for the prediction of trends in nanoparticle transport in vivo. Overall, the results reported herein serve to demonstrate important determinants of nanoparticle intratumoral transport and to establish computational in vitro and in vivo methodologies for the rational design and optimization of nanomedicines.

Activated Carbon was produced from strong cation-exchange resins, sulphonated styrene divinylbenzene copolymers originally in H+ form, by means of carbonization and steam activation in an electrical furnace. One macroporous resin produced by BAYER Chemicals Inc., Lewatit MonoPlus SP 112 H, was used in the research. Products of carbonization and activation were characterized by using BET, Mercury Porosimetry, Helium Pycnometry and SEM techniques. The effect of carbonization time and temperature on the BET surface areas of the resins were also investigated. Two sets of carbonization experiments (Set 1 and 2) were performed in which time and temperature were varied in order to study their effects on the BET surface areas of the products. In activation experiments (Set 3), carbonized ion-exchangers (600 oC, 1 hr) were activated with steam at 900&deg / C, changing the time of activation and the steam flow rate. The temperatures of the water bath used for steam generation were selected as 60&deg / C, 80&deg / C and 90&deg / C. The pore structures of activated carbons were determined by proper techniques. The volume and area of macropores in the pore diameter range of 8180-50 nm were determined by mercury intrusion porosimetry. Mesopore (in the range of 50-2 nm) areas and volumes were determined by N2 gas adsorption technique at -195.6oC, BET surface areas of the samples were also determined, in the relative pressure range of 0.05 to 0.02, by the same technique. The pore volume and the area of the micropores with diameters less than 2 nm were determined by CO2 adsorption measurements at 0oC by the application of Dubinin Radushkevich equation. In the experiments of Sets 1 and 2, the BET surface area results of the six different carbonization times ranging from 0.5 to 3 hours gave almost the same value with a maximum deviation of 5% from the average showing almost no effect on the areas of the products. In the experiments of Set 3 , the sample activated at 800&deg / C for 6 hrs had the highest BET area, 2130 m2/g, and the one activated at 800&deg / C for 1 hr had the lowest BET area 636 m2/g. N2 adsorption/ desorption isotherms showed no distinct hysteresis indicating a cylindrical geometry of the pores. Adsorption isotherms further indicated that the pores are both highly microporous and mesoporous. N2 (BET) and CO2 (D-R) surface areas of the samples were in the range of 636-2130m2/g and 853-1858 m2/g, respectively. Surface areas of the samples consisted of about 8-53% mesopores and 47-92% micropores.