Over the last two centuries, the discovery and application of catalysts has had a substantial impact on how and what chemicals are produced.Given their broad significance, our group has focused on developing new catalyst systems that are recoverable and reusable, in an attempt to reduce concomitant costs. Our efforts have centered on constructing a recyclable chiral heterogeneous catalyst capable of effecting asymmetric hydrogenations of olefins with high stereoselectivity. A class of phosphinoimidazoline ligands, developed by researchers at Boehringer-Ingelheim, known as BIPI ligands, have proven efficacious in the asymmetric reduction of alkenes. However, these chiral ligands are homogeneous and coordinated to precious metals, rendering them irrecoverable and expensive. To address these issues, our group has derivatized the BIPI ligand-metal complex and immobilized it to the surface of graphene oxide as well as polystyrene. Their efficacy and recyclability toward the asymmetric hydrogenation of a functionalized olefin have been evaluated. Another facet of our work has included developing a cost effective synthetic process to artemisinin, the gold standard drug in the treatment of malaria.As a natural product, artemisinin’s worldwide supply remains highly unpredictable, contributing to great price volatility.Combining the benefits of catalysis and the advantages of continuous flow chemistry, our research has sought to develop an economical approach to convert a biosynthetic precursor, artemisinic acid, to artemisinin in three chemical transformations. High-throughput experimentation allowed us to screen a prodigious number of catalysts and identify those effective in the asymmetric hydrogenation artemisinic acid to dihydroartemisinic acid, the first step in the transformation. This screening directed us to an inexpensive, heterogeneous ruthenium catalyst. The second step of the process includes the photooxygenation of dihydroartemisinic acid, which involves photochemically generated singlet oxygen. We have evaluated a commercially available heterogeneous photocatalyst packed in a transparent bed, surrounded by light emitting diodes in the continuous photooxygenation of dihydroartemisinic acid to dihydroartemisinic acid hydroperoxide. The third and final step, an acid induced hock cleavage, initiates an intricate cascading reaction that installs an endoperoxide bridge to deliver artemisinin. Our process afforded a 57% yield from dihydroartemisinic acid to artemisinin.

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.

An experimental and modelling investigation of a tetrafunctional initiator designed for free radical polymerizations is presented. Multifunctional initiators are believed to provide two advantages over traditional monofunctional initiators. With a higher number of functional sites per molecule, they are able to increase polymer production while simultaneously maintaining or increasing polymer molecular weight. Examination of the literature indicates the majority of academic and industrial published studies have investigated difunctional initiators with most focusing on styrene. In this thesis, a tetrafunctional initiator, JWEB50, was systematically investigated for a variety of monomer systems in order to develop a better understanding of the behaviour of multifunctional initiators in free radical polymerizations. <br /><br /> A kinetic study comparing the tetrafunctional initiator to a monofunctional counterpart, TBEC, demonstrated that the impact of a multifunctional initiator is dependent upon monomer type. Regardless of the homo- or copolymer system examined, it was observed that the tetrafunctional initiator could produce higher rates of polymerization due to the greater number of labile groups per initiator molecule. However, the influence of the tetrafunctional initiator on the polymer molecular weight was dictated by the polymerization characteristics of the system in question. In the case of styrene, the tetrafunctional initiator maintained similar molecular weights compared to the monofunctional initiator while for methyl methacrylate (MMA), switching from a mono- to a tetrafunctional initiator actually decreased the polymer molecular weight. Other monomers such as butyl acrylate and vinyl acetate and copolymers of MMA and styrene or alpha-methyl styrene were examined to study the effect of initiator functionality in free radical polymerizations. <br /><br /> Subsequent to the kinetic investigation, polystyrene and poly(methyl methacrylate) samples produced with the tetrafunctional initiator were characterized in detail in order to examine the effects of initiator functionality on polymer properties. Samples generated with the monofunctional initiator were used for comparison purposes. Chromatographic and dilute solution methods were able to detect significant levels of branching in the polystyrene sample produced with JWEB50, while poly(methyl methacrylate) samples showed no evidence of branching. Rheological tests involving a combination of oscillatory and creep shear measurements were completed in order to detect differences between samples. The presence of branching using rheological techniques was clearly observed for both polystyrene and poly(methyl methacrylate) samples produced with the tetrafunctional initiator. <br /><br /> In order to explain the experimental results observed in the kinetic and polymer properties studies, a reaction mechanism for polymerizations initiated with a tetrafunctional initiator was proposed and used in the development of a mathematical model. Reactions involving the fate/efficiency of functional groups are properly accounted for, while in the past this had been ignored by modelling work in the literature. Based on model predictions, di-radical concentrations were estimated to be several orders of magnitude smaller than mono-radical concentrations and their contribution in the reaction mechanism was found to be negligible. Modelling results also demonstrated that the concentration and chain length of various polymer structures (i. e. , linear, star or coupled stars) depend upon monomer type and reaction conditions.

An experimental and modelling investigation of a tetrafunctional initiator designed for free radical polymerizations is presented. Multifunctional initiators are believed to provide two advantages over traditional monofunctional initiators. With a higher number of functional sites per molecule, they are able to increase polymer production while simultaneously maintaining or increasing polymer molecular weight. Examination of the literature indicates the majority of academic and industrial published studies have investigated difunctional initiators with most focusing on styrene. In this thesis, a tetrafunctional initiator, JWEB50, was systematically investigated for a variety of monomer systems in order to develop a better understanding of the behaviour of multifunctional initiators in free radical polymerizations. <br /><br /> A kinetic study comparing the tetrafunctional initiator to a monofunctional counterpart, TBEC, demonstrated that the impact of a multifunctional initiator is dependent upon monomer type. Regardless of the homo- or copolymer system examined, it was observed that the tetrafunctional initiator could produce higher rates of polymerization due to the greater number of labile groups per initiator molecule. However, the influence of the tetrafunctional initiator on the polymer molecular weight was dictated by the polymerization characteristics of the system in question. In the case of styrene, the tetrafunctional initiator maintained similar molecular weights compared to the monofunctional initiator while for methyl methacrylate (MMA), switching from a mono- to a tetrafunctional initiator actually decreased the polymer molecular weight. Other monomers such as butyl acrylate and vinyl acetate and copolymers of MMA and styrene or alpha-methyl styrene were examined to study the effect of initiator functionality in free radical polymerizations. <br /><br /> Subsequent to the kinetic investigation, polystyrene and poly(methyl methacrylate) samples produced with the tetrafunctional initiator were characterized in detail in order to examine the effects of initiator functionality on polymer properties. Samples generated with the monofunctional initiator were used for comparison purposes. Chromatographic and dilute solution methods were able to detect significant levels of branching in the polystyrene sample produced with JWEB50, while poly(methyl methacrylate) samples showed no evidence of branching. Rheological tests involving a combination of oscillatory and creep shear measurements were completed in order to detect differences between samples. The presence of branching using rheological techniques was clearly observed for both polystyrene and poly(methyl methacrylate) samples produced with the tetrafunctional initiator. <br /><br /> In order to explain the experimental results observed in the kinetic and polymer properties studies, a reaction mechanism for polymerizations initiated with a tetrafunctional initiator was proposed and used in the development of a mathematical model. Reactions involving the fate/efficiency of functional groups are properly accounted for, while in the past this had been ignored by modelling work in the literature. Based on model predictions, di-radical concentrations were estimated to be several orders of magnitude smaller than mono-radical concentrations and their contribution in the reaction mechanism was found to be negligible. Modelling results also demonstrated that the concentration and chain length of various polymer structures (i. e. , linear, star or coupled stars) depend upon monomer type and reaction conditions.

The development of a chip-based sensor array composed of individually addressable polystyrene-polyethylene glycol and agarose microspheres has been demonstrated. The microspheres are selectively arranged in micromachined cavities localized on silicon wafers. These cavities are created with an anisotropic etch and serve as miniaturized reaction vessels and analysis chambers. The cavities possess pyramidal pit shapes with trans-wafer openings that allow for both fluid flow through the microreactors/analysis chambers as well optical access to the chemically sensitive microspheres. Identification and quantification of analytes occurs via colorimetric and fluorescence changes to receptor and indicator molecules that are covalently attached to termination sites on the polymeric microspheres. Spectral data is extracted from the array efficiently using a charge-coupled device (CCD) allowing for the near-real-time digital analysis of complex fluids. The power and utility of this new microbead array detection methodology is demonstrated here for the analysis of complex fluids containing a variety of important classes of analytes including acids, bases, metal cations, sugars and antibody reagents. The application of artificial neural network analyses to the microbead array is demonstrated in the context of pH measurements. To assess the utility of the analysis and gain an understanding of the molecular level design of the sensor, parameters such as the choice of the indicator dyes, array size, data pre-processing techniques, as well as different network types and architectures were evaluated. Additionally, the development of miniaturized chromatographic systems localized within individual polymer microspheres and their incorporation into an array is reported. The integrated chromatographic and detection concept is based on the creation of distinct functional layers within the microspheres. Such beads have been incorporated into the array platform and used for speciation and concentration determination of aqueous metal cation solutions. / text

Τα συμπολυμερή κατά συστάδες (block copolymers) έχουν κεντρίσει το ενδιαφέρον αρκετών ερευνητών όχι μόνο για το γεγονός ότι τα τμήματα από τα οποία αποτελούνται βρίσκονται στην νάνο-κλίμακα, αλλά και λόγω των ποικίλων φυσικών και μηχανικών ιδιοτήτων που εμφανίζουν, εξαιτίας της ικανότητας τους να αυτό-οργανώνονται (self assembly materials) σε διάφορες μορφολογίες. Η όχι και τόσο εύκολη διαδικασία παρασκευής συμπολυμερών κατά συστάδες πραγματοποιείται εμπλέκοντας σε αυτή παράγοντες, ανάλογα με το επιθυμητό αποτέλεσμα, όπως το μοριακό βάρος, τη νανοδομή και τη σύσταση. Στην παρούσα εργασία μελετήθηκαν και συγκρίθηκαν οι δυναμικές και στατικές ιδιότητες πρωτότυπων συμπολυμερών δύο και τριών συστάδων, γραμμικής και ετεροκλαδικής αστεροειδούς αρχιτεκτονικής ΑΒ, ΑΒC, AnBn και An(B-C)n, καθώς και η επίδραση διαφόρων παραγόντων στις παραπάνω ιδιότητες. Τα συμπολυμερή παρασκευάστηκαν μέσω «ζωντανού» ανιονικού πολυμερισμού, όπου οι κλάδοι των αστεροειδών συμπολυμερών ήταν συνδεδεμένοι σε ένα πυρήνα. Η Α φάση ήταν πολυστυρόλιο (PS), η Β φάση ήταν ανάλογα την περίπτωση πολυμεθακρυλικός εξυλεστέρας (ΡΗΜΑ) ή πολυμεθακρυλικός αιθυλεστέρας (ΡΕΜΑ) και η C φάση ήταν πολυμεθακρυλικός μεθυλεστέρας (PMMA). Με την ολοκλήρωση της παρούσας διπλωματικής εργασίας, συμπεραίνουμε ότι ο προσεκτικός έλεγχος της μακρο-μοριακής χημείας και ο συνδυασμός της με την μακρο-μηχανική δοκιμή επιτρέπει τον προσδιορισμό όλων των σημαντικών παραμέτρων που επηρεάζουν τη μηχανική συμπεριφορά. Η κατανόηση της επίδρασης των μοριακών παραμέτρων, όπως η επιλογή των κατάλληλων πολυμερών - φάσεων, το ποσοστό συμμετοχής τους καθώς και η αρχιτεκτονική, γραμμική και αστεροειδής διαμόρφωση, στη μηχανική συμπεριφορά είναι δυνατή. Η αστεροειδής αρχιτεκτονική εμφανίζει καλύτερη μηχανική συμπεριφορά από τη γραμμική. Έπειτα, η παρουσία δύο ψαθυρών φάσεων στο ΑnDn, προσδίδουν υψηλό μέτρο ελαστικότητας και αντοχή καθώς και ικανοποιητική ολκιμότητα. Ακόμα, η προσθήκη του PHMA, ως φάση Β επέφερε αυξημένη ολκιμότητα και ικανοποιητική αντοχή / μέτρο ελαστικότητας, ενώ η εισαγωγή του PMMA, ως φάση C στα αστεροειδή συμπολυμερή δεν επέφερε σημαντικές αλλαγές στις μηχανικές ιδιότητες. Τέλος ο αριθμός των κλάδων είχε θετική επίδραση στη μηχανική συμπεριφορά των αστεροειδών. / Block copolymers have recently received much attention not only for the fact that their components are in nano-scale size but also for the various natural and mechanical properties that they present because of their self-organization ability in various morphologies (self–assembly materials). The production process of block copolymers is realized easily, involving factors as the molecular weight, the nanostructure and the composition. In present work were studied and compared the dynamic and static mechanical properties of new copolymers with two and three blocks having linear and star architecture , AB, ABC, AnBn and An(B-b-C)n, as well as the effect of various factors in the properties above. Block copolymers were prepared via “living” anionic polymerization, where the arms of star block copolymers were connected in one core. The phase A was PS, the B phase was PHMA or PEMA proportionally the case and the C phase was PMMA. Finishing of present work, we conclude that the careful control of macromolecular chemistry and her combination with macro-mechanical test allow the determination of all important parameters that influence the mechanical behavior. The comprehension of effect of molecular parameters such as the choice of suitable polymers – phases, the percent of each component and the architecture, linear and star configuration, in the mechanical properties are possible. Star architecture shows better mechanic behavior than linear. Also, the presence of two glassy phases in AnDn gives high strength/ modulus and reasonable ductility. The addition of PHMA as phase B gave an increase in ductility and reasonable strength modulus. Finally, the addition of PMMA, as phase C in star copolymers did not have an important changes while the number of arm had positive effect in the mechanical properties.

Αντικείμενο της Διατριβής αποτελεί η διερεύνηση των δυνατοτήτων του Γεωαφρού Διογκωμένης Πολυστερίνης (ΓΔΠ) για τη χρησιμοποίησή του ως σεισμικό μονωτικό παρέμβλημα σε συμβατικούς τοίχους εδαφικής αντιστήριξης (τύπου βαρύτητας ή προβόλου) καθώς και σε ακρόβαθρα γεφυρών. Η παρούσα έρευνα βασίζεται στην αριθμητική ανάλυση της συμπεριφοράς συμβατικών τοίχων αντιστήριξης κάτω από τη δράση οριζόντιας σεισμικής διέγερσης βάσης. Οι αναλύσεις διεξάγονται τόσο για μη-μονωμένους τοίχους όσο και για τοίχους σεισμικά μονωμένους με παρέμβλημα ΓΔΠ. Το παρέμβλημα έχει τη μορφή κατακόρυφου φύλλου μικρού σχετικά πάχους που τοποθετείται σε επαφή με την πίσω όψη του τοίχου παρεμβαλλόμενο μεταξύ τοίχου και επιχώματος. Οι αναλύσεις διεξάγονται χρησιμοποιώντας τη μέθοδο πεπερασμένων στοιχείων (κώδικας PLAXIS v.8) με την παραδοχή ιξωδοελαστικής συμπεριφοράς εδαφικού επιχώματος και κατακόρυφου ελαστικού τοίχου δεδομένης ευκαμψίας και στροφικής αντίστασης της βάσης. Ως δυναμική διέγερση βάσης χρησιμοποιούνται αρμονικές χρονοϊστορίες επιτάχυνσης μεταβαλλόμενου εύρους και συχνότητας. Κατ’ αρχήν αξιολογείται η αξιοπιστία της χρησιμοποιούμενης μεθόδου ανάλυσης και τα αποτελέσματα των αναλύσεων συγκρίνονται με ανάλογα δημοσιευμένα αποτελέσματα και διαπιστώνεται πολύ καλή συμφωνία όσον αφορά την τιμή της σεισμικής ώθησης και το ύψος εφαρμογής της από τη βάση του τοίχου. Για την περίπτωση των σεισμικά μονωμένων (με παρέμβλημα ΓΔΠ) τοίχων οι εξεταζόμενες παράμετροι περιλαμβάνουν το σχήμα του παρεμβλήματος, την πυκνότητα και το ποσοστιαίο (σε σχέση με το ύψος του τοίχου) πάχος του ΓΔΠ, tr, την ευκαμψία του τοίχου, την καθ’ ύψος μεταβολή του μέτρου ελαστικότητας του ΓΔΠ και τη συχνότητα διέγερσης της βάσης. Η αποτελεσματικότητα της σεισμικής μόνωσης περιγράφεται ποσοτικά με τον συντελεστή Ar που ορίζεται ως το επί τοις εκατό ποσοστό της μείωσης (λόγω μόνωσης) της σεισμικής ώθησης σε σχέση με την τιμή που προκύπτει χωρίς μόνωση. Σχετικά με το σχήμα του παρεμβλήματος (κατά την έννοια του ύψους του τοίχου) διεξήχθησαν αναλύσεις για ορθογωνικό σχήμα και τρία τριγωνικά σχήματα και τα αποτελέσματα υποδεικνύουν ότι η βέλτιστη αποτελεσματικότητα επιτυγχάνεται με χρήση ορθογωνικού σχήματος. Επίσης διαπιστώθηκε ότι είναι δυνατή η επίτευξη τιμών της αποτελεσματικότητας σεισμικής μόνωσης Ar>50% για τιμές πάχους παρεμβλήματος tr 15%. Τα αποτελέσματα υποδεικνύουν επίσης ότι, επειδή η προκύπτουσα σχέση Ar - tr είναι μη γραμμική, απαιτούνται σχετικά μεγάλα πάχη παρεμβλήματος για τη μείωση της σεισμικής ώθησης σε ποσοστό μεγαλύτερο του 50%. Τέλος, για τον αντισεισμικό σχεδιασμό τοίχων αντιστήριξης προτείνεται δοκιμαστικά η εφαρμογή διαδικασίας που βασίζεται στον ΕΑΚ 2000, χρησιμοποιώντας όμως διπλάσια τιμή για το συντελεστή συμπεριφοράς, qw, εφόσον επιδιώκεται η επίτευξη αποτελεσματικότητας Ar=50%. / The objective of the Thesis is the investigation of the possibility to use the Expanded Polystyrene Geofoam (EPS Geofoam) for the seismic isolation of earth retaining walls. The research is based on the results of numerical analyses (using the finite element method) for determining the response of vertical walls supporting horizontal backfill and subjected to horizontal harmonic base excitation. The seismic isolation is realized by placing a column of EPS geofoam (compressible inclusion) between the back-face of the wall and the backfill. The response is calculated by using elastic analysis (with viscous damping for the backfill material). The efficiency of seismic isolation is quantitavely described by the Isolation Efficiency, Ar, defined as the ratio (in percent) of the reduction of earthquake thrust (due to isolation) to the earthquake thrust without isolation. The parameters investigated are the shape of the inclusion, the density and the (percent) thickness, tr, of the EPS geofoam, the wall flexibility, the variation of EPS geofoam modulus of elasticity with depth as well as the amplitude and frequency of excitation. The results of the analyses indicate that the optimum shape of the inclusion is the orthogonal (i.e. constant thickness with depth) whereas the effect of the inhomogeneity of the EPS geofoam along the depth of the wall is negligible, as long as the analysis is conducted using a constant mean value for the Modulus of Elasticity of EPS. The results also indicate that an Isolation Efficiency of about 50% may be achieved by using an inclusion thickness of about 15% of the wall height. Due to the nonlinearity of the relation Ar – tr, further increase of the inclusion thickness has a minor effect on the isolation efficiency of the inclusion. Based on the results of all analyses a tentative procedure is proposed for the earthquake resistant design of earth retaining walls. According to the procedure, the wall is designed following the methodology of the Hellenic Seismic Code (2000) and using qw values twice as those indicated by the Code. The required thickness of the EPS inclusion, tr, is then selected from a diagram relating the tr value to the flexibility of the wall and the density of the inclusion.

The composite material of different density, where porous cement paste serves as matrix and crushed waste expanded polystyrene packages serve as inclusions, was developed. The compositions of formative mixtures and technological parameters of production for this composite material were selected and its properties were investigated. / Sukurta skirtingo tankio kompozitinė medžiaga, kurioje matrica yra poringoji cemento tešla, o intarpai - trupintos polistireninio putplasčio pakavimo taros atliekos. Parinktos minėtos kompozitinės medžiagos formavimo mišinių sudėtys, gamybos technologiniai parametrai ir ištirtos jos bandinių savybės.

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.

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.