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. / Master of Science

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. / Ph. D.

Cross-linked poly(ethylene oxide) (XLPEO) based on poly(ethylene glycol) diacrylate (PEGDA) is an amorphous rubbery material with potential applications for carbon dioxide removal from mixtures with light gases such as methane, hydrogen, oxygen and nitrogen. Changing the polymer network structure of XLPEO through copolymerization has previously been shown to influence gas transport properties, which correlated with fractional free volume according to the Cohen-Turnbull model. This project explores strategic modifications of the cross-linked polymer structure and their effect on the chemical, physical and gas transport properties with an aim to develop rational, molecular-based design rules for tailoring separation performance. Experimental results from calorimetric and dynamic thermal analysis studies are presented, along with pure gas permeability and solubility obtained at 35°C. Incorporation of dangling side chains by copolymerization of PEGDA with methoxy-terminated poly(ethylene glycol) methyl ether acrylate, n=8 (PEGMEA) was previously shown to be effective in increasing fractional free volume of XLPEO through the opening of local free volume elements, which in turn increased CO₂ permeability. Through a comparative study ofshort chain analogs to these co-monomers, incorporation of an ethoxy-terminated co-monomer was shown to be more effective than a comparable methoxy-terminated co-monomer in increasing gas permeability. For instance, copolymerization of PEGDA with 71 wt% ethoxy-terminated diethylene glycol ethyl ether acrylate increased CO₂ permeability from 110 barrer to 320 barrer. Gas permeability increase was not observed when hydroxy or phenoxy-terminated pendants were introduced, which was attributed to reduction in chain mobility due to increased inter-chain chemical interactions or steric restrictions, respectively. Based on these results, incorporation of a co-monomer containing a bulky non-polar terminal group, tris-(trimethylsiloxy)silyl, was examined in order to further increase gas permeability. Addition of 80 wt% TRIS-A co-monomer increased CO₂ permeability of cross-linked PEGDA to 800 barrer. However, the resulting changes in chemical character of the copolymer reduced CO₂/light gas selectivity, even as gas permeability increased. The effect of incorporating a bulky, stiff functional group in the cross-linker chain was studied using cross-linked bisphenol-A ethoxylate diacrylate, which showed 40% increase in permeability compared to cross-linked PEGDA. This study affirmed the importance of polymer chain interaction, in addition to free volume, in determining the gas transport properties of the polymer. / text

Compósitos de Poli (óxido de etileno) (PEO) com diferentes concentrações de argila montmorilonita SWy-1 foram preparados pelo método de intercalação em solução. Os filmes obtidos foram caracterizados por difração de raios X (DRX), microscopia eletrônica de varredura (MEV) e espectrocopia de infravermelho com transformada de Fourier (FTIR). Os resultados de DRX mostraram que os compósitos obtidos foram do tipo intercalados. As imagens de MEV indicaram a existência de agregados de argila SWy-1 dispersos na matriz polimérica. A influência da argila na estabilidade térmica e na cristalização do PEO foi estudada por termogravimetria (TG) e calorimetria exploratória diferencial (DSC). As curvas TG mostraram que a temperatura inicial de degradação térmica (Ti) diminui com o aumento da concentração de SWy-1. Além disso, uma pequena diminuição na amplitude do pico de fusão do PEO foi observado nos resultados de DSC. Os filmes de PEO e dos compósitos de PEO/SWy-1 foram irradiados com luz UV e a fotooxidação foi acompanhada por cromatografia de exclusão por tamanho (SEC). Os resultados de SEC mostraram que a taxa de oxidação do PEO puro foi mais rápida em comparação aos compósitos de PEO/SWy-1. Nesse caso a argila pode ser considerada como um estabilizante contra a irradiação UV. O efeito de estabilizantes do tipo absorverdores de UV (moléculas derivadas da 2-hidroxibenzofenona) e do tipo HALS (Tinuvin 770), quando adicionados ao PEO e ao compósito de PEO/SWy-1, também foi analisado por SEC após a fotooxidação dos filmes. Os resultados mostraram que a adição do estabilizante Tinuvin 770 proporcionou maior estabilidade a matriz polimérica durante o processo degradativo, comparado ao estabilizante 2-hidroxibenzofenona. / Poly(ethylene oxide) (PEO) composites with different concentrations of SWy-1 montmorillonite clay were prepared by solution intercalation method. The thin films obtained were characterized by X-ray diffraction (XRD), scanning electronic microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The XRD results showed that the composites obtained were of the type intercalated. The SEM images have indicated that there are SWy-1 clay aggregates scattered in the polymer matrix. The influence of clay on thermal stability, melting and polymer crystallization processes was studied by thermogravimetric analysis (TG) and differential scanning calorimetric (DSC). The TG curves showed that the initial thermal degradation temperature (Ti) decrease with increasing concentration of SWy-1. Besides, a small decrease in the amplitude of the melting peak of PEO was observed in the DSC results. The thin films of PEO and PEO/SWy-1 composites were exposed to UV irradiation and the photodegradation was accompanied by size exclusion chromatography (SEC). The SEC results showed that the rate of oxidation of pristine PEO was faster compared to PEO/SWy-1 composites. In this case the clay can be considered as a stabilizer against UV irradiation. The effect of UV absorbers (2-hydroxybenzophenone derivated molecules) and HALS (Tinuvin 770) stabilizers, when added to PEO and PEP/SWy-1 composites, also were studied by SEC after the thin films photodegradation. The results allowed to conclude that the polymer matrix became more stable for degradation with adition of Tinuvin 770 stabilizer when compared to 2-hydroxybenzophenone.

Compósitos de Poli (óxido de etileno) (PEO) com diferentes concentrações de argila montmorilonita SWy-1 foram preparados pelo método de intercalação em solução. Os filmes obtidos foram caracterizados por difração de raios X (DRX), microscopia eletrônica de varredura (MEV) e espectrocopia de infravermelho com transformada de Fourier (FTIR). Os resultados de DRX mostraram que os compósitos obtidos foram do tipo intercalados. As imagens de MEV indicaram a existência de agregados de argila SWy-1 dispersos na matriz polimérica. A influência da argila na estabilidade térmica e na cristalização do PEO foi estudada por termogravimetria (TG) e calorimetria exploratória diferencial (DSC). As curvas TG mostraram que a temperatura inicial de degradação térmica (Ti) diminui com o aumento da concentração de SWy-1. Além disso, uma pequena diminuição na amplitude do pico de fusão do PEO foi observado nos resultados de DSC. Os filmes de PEO e dos compósitos de PEO/SWy-1 foram irradiados com luz UV e a fotooxidação foi acompanhada por cromatografia de exclusão por tamanho (SEC). Os resultados de SEC mostraram que a taxa de oxidação do PEO puro foi mais rápida em comparação aos compósitos de PEO/SWy-1. Nesse caso a argila pode ser considerada como um estabilizante contra a irradiação UV. O efeito de estabilizantes do tipo absorverdores de UV (moléculas derivadas da 2-hidroxibenzofenona) e do tipo HALS (Tinuvin 770), quando adicionados ao PEO e ao compósito de PEO/SWy-1, também foi analisado por SEC após a fotooxidação dos filmes. Os resultados mostraram que a adição do estabilizante Tinuvin 770 proporcionou maior estabilidade a matriz polimérica durante o processo degradativo, comparado ao estabilizante 2-hidroxibenzofenona. / Poly(ethylene oxide) (PEO) composites with different concentrations of SWy-1 montmorillonite clay were prepared by solution intercalation method. The thin films obtained were characterized by X-ray diffraction (XRD), scanning electronic microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The XRD results showed that the composites obtained were of the type intercalated. The SEM images have indicated that there are SWy-1 clay aggregates scattered in the polymer matrix. The influence of clay on thermal stability, melting and polymer crystallization processes was studied by thermogravimetric analysis (TG) and differential scanning calorimetric (DSC). The TG curves showed that the initial thermal degradation temperature (Ti) decrease with increasing concentration of SWy-1. Besides, a small decrease in the amplitude of the melting peak of PEO was observed in the DSC results. The thin films of PEO and PEO/SWy-1 composites were exposed to UV irradiation and the photodegradation was accompanied by size exclusion chromatography (SEC). The SEC results showed that the rate of oxidation of pristine PEO was faster compared to PEO/SWy-1 composites. In this case the clay can be considered as a stabilizer against UV irradiation. The effect of UV absorbers (2-hydroxybenzophenone derivated molecules) and HALS (Tinuvin 770) stabilizers, when added to PEO and PEP/SWy-1 composites, also were studied by SEC after the thin films photodegradation. The results allowed to conclude that the polymer matrix became more stable for degradation with adition of Tinuvin 770 stabilizer when compared to 2-hydroxybenzophenone.

Neste trabalho, dois macro-agentes de transferência de cadeia para polimerizações via RAFT, à base de poli(óxido de etileno), isto é, PEO-CPADB e PEO-CPP, foram sintetizados via duas rotas químicas e utilizados como estabilizantes coloidais e como agentes de controle de massa molecular na polimerização em miniemulsão do estireno. Látices de poliestireno (PS), estabilizados estericamente pelos segmentos de PEO, foram obtidos utilizando 2,2\'-azobis(isobutironitrila) como iniciador e hexadecano como co-estabilizador. O consumo de monômero foi determinado via análise gravimétrica. O tamanho de partícula e a distribuição de tamanhos de partículas (PSD) foram determinados por espalhamento de luz (LS). As massas moleculares e a distribuição de massas moleculares (nwMM) dos polímeros foram determinadas por cromatografia de exclusão de tamanho (SEC). Os resultados mostraram que o diâmetro das gotas e das partículas de polímero, assim como a estabilidade coloidal dos látices são fortemente dependentes do tipo e da quantidade de agente de transferência de cadeia utilizado nas polimerizações. Deslocamentos das curvas de distribuição de massas moleculares para massas moleculares maiores, em função da conversão, indicaram que a maioria das cadeias poliméricas apresentava características de cadeias vivas. Análises de GPC também mostraram que a polimerização foi bem controlada quando uma quantidade do macro-agente RAFT PEO-CPP, igual a 4,4 x 10-3 mol.L-1 foi utilizada, o que foi indicado pelo baixos índices de polidispersão obtidos (1,05-1,42). / In this work, two poly(ethylene oxide)-based macro-RAFT agents, ie, PEO-CPADB and PEO-CPP, were synthesized via two chemical routes and used as a stabilizer and a control agent in the miniemulsion polymerization of styrene. Polystyrene (PS) latexes sterically stabilized by the PEO segments were obtained using 2,2?-azobis(isobutyronitrile) as initiator and hexadecane as co-stabilizer. Monomer consumption was monitored by gravimetric analysis. The latex particle size and the particle size distribution (PSD) were measured by light scattering (LS). Molar masses and molar mass distributions (nwMM) of the polymers were determined by size exclusion chromatography (SEC). The results showed that the droplet/particle sizes and the latexes stability are strongly dependent on the type and on the amount of macro-RAFT agent used in the polymerizations. Shifts of the SEC chromatograms toward higher molar masses with conversion indicated that the majority of the polymer chains are living chains. Size Exclusion Chromatography (SEC) analysis also showed that polymerization was well controlled when an amount of macro-RAFT PEO-RAFT agent equal to 4.4 x 10-3 mol. L-1 was used, since low polidispersity indices (1.05-1.42) was achieved.

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.

Vienas iš šiuolaikinės polimerų chemijos uždavinių – gauti numatytos molekulinės masės ir architektūros polimerines medžiagas. Neseniai buvo sukurti nauji radikalinės polimerizacijos metodai, kurie priskiriami gyvybingajai (valdomai) polimerizacijai (GRP). Makromonomerų (MM) gyvybingoji radikalinė polimerizacija yra efektyvus būdas gauti šepetinius (cilindrinius) polimerus). Šepetiniai polimerai – tai makromolekulės, kuriose prie pagrindinės polimerinės grandinės prijungta daug šoninių mažesnės molekulinės masės polimerinių (oligomerinių) grandinių. Dėl tarp šoninių grandinių esančių erdvinės stūmos jėgų tokios makromolekulės įgauna neįprastų savybių, pvz., standumą, cilindrinę formą, didelį segmentų tankį. Pagrindinis šio darbo tikslas buvo susintetinti norimos sudėties šepetinius polielektrolitinius polimerus, sudarytus iš krūvį turinčios poli(met)akrilato pagrindinės grandinės ir šoninių polietilenoksido grandinių, ir ištirti jų savybes. Svarbiausieji šio darbo rezultatai, atspindintys jo naujumą, originalumą ir svarbą: Pirmą kartą nuodugniai ištirta metakrilo rūgšties (MAR) ir dviejų skirtingų molekulinių masių polietilenoksido metakrilatų PEOnMEMA (n = 5, 45) kopolimerizacija įprastiniu radikaliniu ir RAFT metodais. Sukurta metodika PEO makromonomerų kopolimerizacijos kinetikai tirti, užrašant 1H BMR spektrus in situ ir įvertinant likutinę monomerų koncentraciją reakcijos mišinyje bei momentinę kopolimero sudėtį iki gilių konversijų. Netiesiniu kintamųjų paklaidų metodu... [toliau žr. visą tekstą] / The main goal of this work was to synthesize polyelectrolyte brushes containing poly(ethylene oxide) side chains by living polymerization. Brush-like macromolecules are unique polymer molecules whose conformation and physical properties are controlled by steric repulsion of densely grafted side chains. Molecules can be either flexible or stiff, depending on the grafting density and the length of the side chains. Polymerization of macromonomers is one of the most useful ways to prepare brush copolymers. However, with the macromonomer method, the distribution of the spacing of the side chains cannot be entirely controlled which along with broad and multimodal molecular weight distribution makes these polymers heterogeneous. These problems were considered to be overcome with the use of controlled/living polymerization. Conventional free-radical and RAFT copolymerization of poly(ethylene oxide) substituent containing methacrylate macromonomers, PEO5MEMA and PEO45MEMA, with methacrylic acid (MAA) was studied by the use of 1H NMR spectroscopy for an analysis of residual monomers. RAFT copolymerization of PEO45MEMA and MAA enabled to synthesize comb copolymers with low composition distribution and more homogeneous distribution of PEO side chains along the mainchain. Amphiphilic non-ionic blockcopolymers poly(lauryl methacrylate) (PLMA) – P(PEOnMEMA) and amphiphilic anionic blockcopolymers PLMA – PMAA were prepared by the RAFT method, and their properties in aqueous and THF... [to full text]

The main goal of this work was to synthesize polyelectrolyte brushes containing poly(ethylene oxide) side chains by living polymerization. Brush-like macromolecules are unique polymer molecules whose conformation and physical properties are controlled by steric repulsion of densely grafted side chains. Molecules can be either flexible or stiff, depending on the grafting density and the length of the side chains. Polymerization of macromonomers is one of the most useful ways to prepare brush copolymers. However, with the macromonomer method, the distribution of the spacing of the side chains cannot be entirely controlled which along with broad and multimodal molecular weight distribution makes these polymers heterogeneous. These problems were considered to be overcome with the use of controlled/living polymerization. Conventional free-radical and RAFT copolymerization of poly(ethylene oxide) substituent containing methacrylate macromonomers, PEO5MEMA and PEO45MEMA, with methacrylic acid (MAA) was studied by the use of 1H NMR spectroscopy for an analysis of residual monomers. RAFT copolymerization of PEO45MEMA and MAA enabled to synthesize comb copolymers with low composition distribution and more homogeneous distribution of PEO side chains along the mainchain. Amphiphilic non-ionic blockcopolymers poly(lauryl methacrylate) (PLMA) – P(PEOnMEMA) and amphiphilic anionic blockcopolymers PLMA – PMAA were prepared by the RAFT method, and their properties in aqueous and THF... [to full text] / Vienas iš šiuolaikinės polimerų chemijos uždavinių – gauti numatytos molekulinės masės ir architektūros polimerines medžiagas. Neseniai buvo sukurti nauji radikalinės polimerizacijos metodai, kurie priskiriami gyvybingajai (valdomai) polimerizacijai (GRP). Makromonomerų (MM) gyvybingoji radikalinė polimerizacija yra efektyvus būdas gauti šepetinius (cilindrinius) polimerus). Šepetiniai polimerai – tai makromolekulės, kuriose prie pagrindinės polimerinės grandinės prijungta daug šoninių mažesnės molekulinės masės polimerinių (oligomerinių) grandinių. Dėl tarp šoninių grandinių esančių erdvinės stūmos jėgų tokios makromolekulės įgauna neįprastų savybių, pvz., standumą, cilindrinę formą, didelį segmentų tankį. Pagrindinis šio darbo tikslas buvo susintetinti norimos sudėties šepetinius polielektrolitinius polimerus, sudarytus iš krūvį turinčios poli(met)akrilato pagrindinės grandinės ir šoninių polietilenoksido grandinių, ir ištirti jų savybes. Svarbiausieji šio darbo rezultatai, atspindintys jo naujumą, originalumą ir svarbą: Pirmą kartą nuodugniai ištirta metakrilo rūgšties (MAR) ir dviejų skirtingų molekulinių masių polietilenoksido metakrilatų PEOnMEMA (n = 5, 45) kopolimerizacija įprastiniu radikaliniu ir RAFT metodais. Sukurta metodika PEO makromonomerų kopolimerizacijos kinetikai tirti, užrašant 1H BMR spektrus in situ ir įvertinant likutinę monomerų koncentraciją reakcijos mišinyje bei momentinę kopolimero sudėtį iki gilių konversijų. Netiesiniu kintamųjų paklaidų metodu... [toliau žr. visą tekstą]

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.