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The remarkable antifouling properties of zwitterionic polymers in controlled environments are often counteracted by their delicate mechanical stability. In order to improve the mechanical stabilities of zwitterionic hydrogels, the effect of increased crosslinker densities was thus explored. In a first approach, terpolymers of zwitterionic monomer 3-[N -2(methacryloyloxy)ethyl-N,N-dimethyl]ammonio propane-1-sulfonate (SPE), hydrophobic monomer butyl methacrylate (BMA), and photo-crosslinker 2-(4-benzoylphenoxy)ethyl methacrylate (BPEMA) were synthesized. Thin hydrogel coatings of the copolymers were then produced and photo-crosslinked. Studies of the swollen hydrogel films showed that not only the mechanical stability but also, unexpectedly, the antifouling properties were improved by the presence of hydrophobic BMA units in the terpolymers.
Based on the positive results shown by the amphiphilic terpolymers and in order to further test the impact that hydrophobicity has on both the antifouling properties of zwitterionic hydrogels and on their mechanical stability, a new amphiphilic zwitterionic methacrylic monomer, 3-((2-(methacryloyloxy)hexyl)dimethylammonio)propane-1-sulfonate (M1), was synthesized in good yields in a multistep synthesis. Homopolymers of M1 were obtained by free-radical polymerization. Similarly, terpolymers of M1, zwitterionic monomer SPE, and photo-crosslinker BPEMA were synthesized by free-radical copolymerization and thoroughly characterized, including its solubilities in selected solvents.
Also, a new family of vinyl amide zwitterionic monomomers, namely 3-(dimethyl(2-(N -vinylacetamido)ethyl)ammonio)propane-1-sulfonate (M2), 4-(dimethyl(2-(N-vinylacetamido)ethyl)ammonio)butane-1-sulfonate (M3), and 3-(dimethyl(2-(N-vinylacetamido)ethyl)ammonio)propyl sulfate (M4), together with the new photo-crosslinker 4-benzoyl-N-vinylbenzamide (M5) that is well-suited for copolymerization with vinylamides, are introduced within the scope of the present work. The monomers are synthesized with good yields developing a multistep synthesis. Homopolymers of the new vinyl amide zwitterionic monomers are obtained by free-radical polymerization and thoroughly characterized. From the solubility tests, it is remarkable that the homopolymers produced are fully soluble in water, evidence of their high hydrophilicity. Copolymerization of the vinyl amide zwitterionic monomers, M2, M3, and M4 with the vinyl amide photo-crosslinker M5 proved to require very specific polymerization conditions. Nevertheless, copolymers were successfully obtained by free-radical copolymerization under appropriate conditions.
Moreover, in an attempt to mitigate the intrinsic hydrophobicity introduced in the copolymers by the photo-crosslinkers, and based on the proven affinity of quaternized diallylamines to copolymerize with vinyl amides, a new quaternized diallylamine sulfobetaine photo-crosslinker 3-(diallyl(2-(4-benzoylphenoxy)ethyl)ammonio)propane-1-sulfonate (M6) is synthesized. However, despite a priori promising copolymerization suitability, copolymerization with the vinyl amide zwitterionic monomers could not be achieved.
Materials derived from renewable resources are highly desirable in view of more sustainable manufacturing. Among the available natural materials, wood is one of the key candidates, because of its excellent mechanical properties. However, wood and wood-based materials in engineering applications suffer from various restraints, such as dimensional instability upon humidity changes. Several wood modification treatments increase water repellence, but the insertion of hydrophobic polymers can result in a composite material which cannot be considered as renewable anymore. In this study, we report on the grafting of the fully biodegradable poly(ε-caprolactone) (PCL) inside the wood cell walls by Sn(Oct)2 catalysed ring-opening polymerization (ROP). The presence of polyester chains within the wood cell wall structure is monitored by confocal Raman imaging and spectroscopy as well as scanning electron microscopy. Physical tests reveal that the modified wood is more hydrophobic due to the bulking of the cell wall structure with the polyester chains, which results in a novel fully biodegradable wood material with improved dimensional stability.
Polysarcosine (Mn = 3650–20 000 g mol−1, Đ ∼ 1.1) was synthesized from the air and moisture stable N-phenoxycarbonyl-N-methylglycine. Polymerization was achieved by in situ transformation of the urethane precursor into the corresponding N-methylglycine-N-carboxyanhydride, when in the presence of a non-nucleophilic tertiary amine base and a primary amine initiator.
Polysarcosine (Mn = 3650–20 000 g mol−1, Đ ∼ 1.1) was synthesized from the air and moisture stable N-phenoxycarbonyl-N-methylglycine. Polymerization was achieved by in situ transformation of the urethane precursor into the corresponding N-methylglycine-N-carboxyanhydride, when in the presence of a non-nucleophilic tertiary amine base and a primary amine initiator.
Chemische und physikalische Eigenschaften von Polymeren können verschiedene Zelltypen unterschiedlich, z. B. hinsichtlich Adhärenz oder Funktionalität, beeinflussen. Die Elastizität eines Polymers beeinflusst vor allem, welche Zugkräfte eine Zelle gegenüber ihrem Substrat entwickeln kann. Das Zellverhalten wird dann über intrazelluläre Rückkopplungsmechanismen reguliert. Die Oberflächenladung und/oder Hydrophilie eines Polymers beeinflusst zunächst die Adsorption von Ionen, Proteinen und anderen Molekülen. Vor allem über die Zusammensetzung, Dichte und Konformation der adsorbierten Komponenten werden anschließend die Wechselwirkungen mit den Zellen vermittelt. Des Weiteren können verschiedene Zelltypen unterschiedliche membranassoziierte Proteine, Zucker und Lipide aufweisen, so dass Polymereigenschaften zellspezifische Effekte bewirken können. Für biotechnologische Anwendungen und für den Einsatz in der regenerativen Medizin gewinnen Polymere, die spezifische Zellreaktionen regulieren können, immer weiter an Bedeutung. Die Isolierung und Kultur von primären Keratinozyten ist noch immer anspruchsvoll und die adäquate Heilung von Hautwunden stellt eine fortwährende medizinische Herausforderung dar. Ein Polymer, das eine bevorzugte Adhärenz von Keratinozyten bei gleichzeitig verminderter Anheftung dermaler Fibroblasten ermöglicht, würde erhebliche Vorteile für den Einsatz in der Keratinozyten-Zellkultur und als Wundauflage bieten. Um den potentiell spezifischen Einfluss bestimmter Polymereigenschaften auf primäre humane Keratinozyten und dermale Fibroblasten zu untersuchen, wurde in der vorliegenden Arbeit ein Zellkultursystem für die Mono- und Cokultur beider Zelltypen entwickelt. Das Testsystem wurde als Screening konzipiert, um den Einfluss unterschiedlicher Polymereigenschaften in mehreren Abstufungen auf die Zellen zu untersuchen. Folgende Parameter wurden untersucht: 1. Vitalität und Dichte adhärenter und nicht-adhärierter Zellen, 2. Schädigung der Zellmembran, 3. selektive Adhärenz von Keratinozyten in Cokultur durch die spezifische immunzytochemische Färbung von Keratin14 und Vimentin. Für die Polymere mit variabler Elastizität wurden zusätzlich die Ablagerung extrazellulärer Matrixkomponenten und die Sekretion löslicher Faktoren durch die Zellen untersucht. Als Modellpolymere für die Variation der Elastizität wurden vernetzte Poly(n-butylacrylate) (cPnBA) verwendet, da deren Elastizität durch den Anteil des Vernetzers eingestellt werden kann. Auf dem weniger elastischen cPnBA zeigte sich in der Cokultur ein doppelt so hohes Verhältnis von Keratinozyten zu Fibroblasten wie auf dem elastischeren cPnBA, so dass ein leichter zellselektiver Effekt angenommen werden kann. Acrylnitril-basierte Copolymere wurden als Modellpolymere für die Variation der Oberflächenladung und Hydrophilie verwendet, da die Eigenschaften durch Art und molaren Anteil des Comonomers eingestellt werden können. Durch Variation des molaren Anteils der Comonomere mit positiver bzw. negativer Ladung, Methacrylsäure-2-aminoethylester-hydrochhlorid (AEMA) und N-3-Aminopropyl-methacrylamid-hydro-chlorid (APMA) bzw. Natriumsalz der 2-Methyl-2-propen-1-sulfonsäure (NaMAS), wurde der Anteil der positiven bzw. negativen Ladung im Copolymer variiert. Durch die Erhöhung des molaren Anteils des hydrophilen Comonomers N-Vinylpyrrolidon (NVP) wurde die Hydrophilie des Copolymers gesteigert. Die Erhöhung des molaren Anteils an positiv geladenem Comonomer AEMA im Copolymer führte tendenziell zu einer höheren Keratinozytendichte, wobei die Fibroblastendichte unverändert blieb. Durch die Erhöhung des molaren Anteils des positiv geladenen Comonomers APMA ergaben sich keine deutlichen Unterschiede in Dichte, Vitalität oder Selektivität der Zellen. Durch die stufenweise Erhöhung des molaren Anteils des negativ geladenen Comonomers NaMAS konnte, wie im Falle von AEMA, eine Tendenz zur verbesserten Keratinozytenadhärenz beobachtet werden. Die Steigerung der Hydrophilie der Copolymere führte sowohl für Keratinozyten als auch für Fibroblasten zu einer reduzierten Adhärenz und Vitalität. In der vorliegenden Doktorarbeit wurde ein Testverfahren etabliert, das die Untersuchung von primären humanen Keratinozyten und primären humanen Fibroblasten in Monokultur und Cokultur auf verschiedenen Polymeren ermöglicht. Die bisherigen Ergebnisse zeigen, dass sich durch die gezielte Modifizierung verschiedener Polymereigenschaften die Adhärenz und Vitalität beider Zelltypen beeinflussen lässt. Die Reduktion der Elastizität sowie die Erhöhung des molaren Anteils geladener Comonomere führten zu einer Zunahme der Keratinozytenadhärenz. Da die Fibroblasten unbeeinflusst blieben, zeigte sich für einige der untersuchten Polymere eine leichte Zellselektivität. Diese könnte durch die weitere Erhöhung der Steifigkeit oder des Anteils geladener Comonomere möglicherweise weiter gesteigert werden.
Block copolymers are receiving increasing attention in the literature. Reports on amphiphilic block copolymers have now established the basis of their self-assembly behavior: aggregate sizes, morphologies and stability can be explained from the absolute and relative block lengths, the nature of the blocks, the architecture and also solvent selectiveness. In water, self-assembly of amphiphilic block copolymers is assumed to be driven by the hydrophobic. The motivation of this thesis is to study the influence on the self-assembly in water of A b B type block copolymers (with A hydrophilic) of the variation of the hydrophilicity of B from non-soluble (hydrophobic) to totally soluble (hydrophilic). Glucose-modified polybutadiene-block-poly(N-isopropylacrylamide) copolymers were prepared and their self-assembly behavior in water studied. The copolymers formed vesicles with an asymmetric membrane with a glycosylated exterior and poly(N-isopropylacrylamide) on the inside. Above the low critical solution temperature (LCST) of poly(N-isopropylacrylamide), the structure collapsed into micelles with a hydrophobic PNIPAM core and glycosylated exterior. This collapse was found to be reversible. As a result, the structures showed a temperature-dependent interaction with L-lectin proteins and were shown to be able to encapsulate organic molecules. Several families of double hydrophilic block copolymers (DHBC) were prepared. The blocks of these copolymers were biopolymers or polymer chimeras used in aqueous two-phase partition systems. Copolymers based on dextran and poly(ethylene glycol) blocks were able to form aggregates in water. Dex6500-b-PEG5500 copolymer spontaneously formed vesicles with PEG as the “less hydrophilic” barrier and dextran as the solubilizing block. The aggregates were found to be insensitive to the polymer's architecture and concentration (in the dilute range) and only mildly sensitive to temperature. Variation of the block length, yielded different morphologies. A longer PEG chain seemed to promote more curved aggregates following the inverse trend usually observed in amphiphilic block copolymers. A shorter dextran promoted vesicular structures as usually observed for the amphiphilic counterparts. The linking function was shown to have an influence of the morphology but not on the self-assembly capability in itself. The vesicles formed by dex6500-b-PEG5500 showed slow kinetics of clustering in the presence of Con A lectin. In addition both dex6500-b-PEG5500 and its crosslinked derivative were able to encapsulate fluorescent dyes. Two additional dextran-based copolymers were synthesized, dextran-b-poly(vinyl alcohol) and dextran-b-poly(vinyl pyrrolidone). The study of their self-assembly allowed to conclude that aqueous two-phase systems (ATPS) is a valid source of inspiration to conceive DHBCs capable of self-assembling. In the second part the principle was extended to polypeptide systems with the synthesis of a poly(N-hydroxyethylglutamine)-block-poly(ethylene glycol) copolymer. The copolymer that had been previously reported to have emulsifying properties was able to form vesicles by direct dissolution of the solid in water. Last, a series of thermoresponsive copolymers were prepared, dextran-b-PNIPAMm. These polymers formed aggregates below the LCST. Their structure could not be unambiguously elucidated but seemed to correspond to vesicles. Above the LCST, the collapse of the PNIPAM chains induced the formation of stable objects of several hundreds of nanometers in radius that evolved with increasing temperature. The cooling of these solution below LCST restored the initial aggregates. This self-assembly of DHBC outside any stimuli of pH, ionic strength, or temperature has only rarely been described in the literature. This work constituted the first formal attempt to frame the phenomenon. Two reasons were accounted for the self-assembly of such systems: incompatibility of the polymer pairs forming the two blocks (enthalpic) and a considerable solubility difference (enthalpic and entropic). The entropic contribution to the positive Gibbs free energy of mixing is believed to arise from the same loss of conformational entropy that is responsible for “the hydrophobic effect” but driven by a competition for water of the two blocks. In that sense this phenomenon should be described as the “hydrophilic effect”.