Poly(2-oxazolines) in biological and biomedical application contexts.

Polyoxazolines of various architectures and chemical functionalities can be prepared in a living and therefore controlled manner via cationic ring-opening polymerisation. They have found widespread applications, ranging from coatings to pigment dispersants. Furthermore, several polyoxazolines are water-soluble or amphiphilic and relatively non-toxic, which makes them interesting as biomaterials. This paper reviews the development of polyoxazoline-based polymers in biological and biomedical application contexts since the beginning of the millennium. This includes nanoscalar systems such as membranes and nanoparticles, drug and gene delivery applications, as well as stimuli-responsive systems

A basis for molecular factories: multifunctionality and immobilization of biomolecule-polymer assemblies

Bio-inspired planar polymer membranes are synthetic membranes designed to be combined with biomolecules such as proteins, enzymes or peptides. These membranes provide both an increased mechanical stability as well as an environment to preserve the functionality of the biomolecules. In this thesis, two different kinds of planar membrane systems are demonstrated. In the first project, a sensor for phenolic compounds based on a bio-inspired polymer membrane was developed. Functional surfaces were generated by combining enzymes with polymer membranes composed of an amphiphilic, asymmetric block copolymer. Firstly, polymer films which were formed at the air-water interface were transferred onto silica solid support, by using the Langmuir-Blodgett method. The films were characterized according to their properties, including film thickness, wettability, topography, and roughness. The most promising membranes were used for enzyme attachment. Two model enzymes, laccase and tyrosinase, were adsorbed to the surface and their activity regarding the conversion of phenolic compounds was measured. This project is described in Chapter 1 in detail. In the second project, the interaction of the model pore-forming peptide melittin was studied in combination with a planar synthetic membrane. The investigation focused the interaction of melittin with amphiphilic block copolymer-based synthetic planar membranes as well as the insertion of melittin into these membranes to induce pore formation. Some specific molecular properties of the block copolymers and of the resulting membranes were selected for the investigation, such as hydrophilic to hydrophobic block ratio, membrane thickness and surface roughness. Through melittin addition to the synthetic membranes, melittin insertion requirements were better understood. This project is described in Chapter 2 in detail. Each chapter contains a separate introduction, material and methods section and conclusion and outlook specific to the project.20 In summary, in this thesis the properties of different combinations and applications of polymer-based membranes with biomolecules were investigated to a deeper level

Design at nano-scale. biomimetic block copolymers for polymer-protein hybrid materials

In this thesis, the synthesis and applications of biomimetic amphiphilic ABA triblock copolymers are discussed. Polydimethylsiloxane hydrophobic middle block was synthesized and end-functionalized. Hydrophilic poly-2-methyl-2-oxazoline blocks were polymerized onto the PDMS macroinitiator, in symmetric cationic ring opening polymerization reaction. The end-groups of the synthesized block copolymers were further functionalized with biotin and methacrylate groups. Block copolymers were designed to self-assemble into vesicular structures in dilute aqueous solutions and the properties of the resulting membranes were tuned by the molecular weight of the hydrophobic blocks and the hydrophilic to hydrophobic ratio. Membranes built from the synthesized triblock copolymers were used to mimic the properties of natural lipid bilayers providing higher stability. Block copolymer membranes were reconstituted with a number of natural membrane proteins, thus introducing biological activity and functionality to synthetic materials. Insertion of a bacterial Aquaporin-Z channel protein into water (and solutes) impermeable polymeric membrane resulted in novel hybrid materials promising great improvement in the area of water purification. High impermeability and stability of the triblock copolymer membranes provided an excellent tool to investigate the influence of environmental conditions on transport properties of Aquaporin-Z. Combining the outer membrane protein F - reconstituted polymer vesicles, encapsulating water-soluble enzymes, with receptor-ligand mediated immobilization resulted in an development of immobilized polymeric nanoreactors system. Its potential relevance is in the field of microfluidics, sensors and single molecule spectroscopy, as well as basic research on sensitive molecules and chemically/biologically active surfaces. Block copolymer membranes, in combination with a complex membrane protein, NADH: Ubiquinone Oxidoreductase, were used in the design of the electron -transfer nanodevice that allows site-specific reactions driven by redox-potential differences. Vesicular morphology of aggregates formed by triblock copolymers in dilute aqueous solutions was also utilized in the studies towards potential applications as a drug delivery platform. Interactions of block copolymers with lipids of different properties are also discussed. The structure of the thesis guides the reader through a general introduction to amphiphilic materials, their selfassembly properties and applications (Chapter 1). Polymer-protein hybrid materials are introduced together with membrane proteins used in this work (Chapter 1). The experimental part is divided into two sections: the first describing synthetic routes and characterization of the block copolymers, and the second in the form of original publications, presenting applications of the block copolymers (Chapter 2). Conclusions drawn from our experiments are presented in Chapter 3 and the outlook of our work is outlined in Chapter 4. Information about the materials and methods used and not presented in original publications is shown in Chapter 5 and literature references listed in Chapter 6

Review on bibliography related to antimicrobials

In this report, a bibliographic research has been done in the field of antimicrobials.In this report, a bibliographic research has been done in the field of antimicrobials. Not all antimicrobials have been included, but those that are being subject of matter in the group GBMI in Terrassa, and others of interest. It includes chitosan and other biopolymers. The effect of nanoparticles is of great interest, and in this sense, the effect of Ag nanoparticles and antibiotic nanoparticles (nanobiotics) has been revised. The report focuses on new publications and the antimicrobial effect of peptides has been considered. In particular, the influence of antimicrobials on membranes has deserved much attention and its study using the Langmuir technique, which is of great utility on biomimetic studies. The building up of antimicrobials systems with new techniques (bottom-up approach), as the Layer-by-Layer technique, can also be found in between the bibliography. It has also been considered the antibiofilm effect, and the new ideas on quorem sensing and quorum quenching.Preprin

Lateral diffusion processes in biomimetic polymer membranes

Molecular self-assembly offers an important bottom-up approach to generate new materials with great potential for applications in nano-, life- and medical- sciences and engineering. The interest in “soft” materials suitable for the generation of artificial, biomimetic membranes has increased rapidly over the last years. These membranes combine the advantages of specificity and efficiency found in nature and the robustness and stability of synthetic materials from polymer science. There are currently two approaches to design biomimetic membranes. One uses natural phospholipids, while the other ones uses synthetic lipid mimics as the advanced alternative, which have shown great mechanical and chemical stability compared to their natural counterparts. This is important for technological application where durable devices are required. Biological membrane proteins, which provide selective and very efficient membrane transport, can be inserted into these synthetic block copolymer membranes. This combination of a synthetic membrane with biological membrane proteins is an intriguing phenomenon because the fundamental requirements for successful insertion are still matter of debate. One important issue is that polymeric membranes have thicknesses that exceed the height of the membrane proteins by several factors and the two lengths actually do not match. However, this significant height mismatch can be overcome by choosing a polymer with high flexibility, which has been shown to allow membrane proteins insertion in their active conformation. Flexibility and fluidity are essential membrane properties allowing successful generation of biomimetic membranes. In this thesis, the fluid properties of synthetic membranes composed of synthetic amphiphiles are studied based on a large library of block copolymers. These consist of poly(2-methyloxazoline) (PMOXA) and poly(dimethylsiloxane) (PDMS) and are used as diblock (PMOXA-b-PDMS, AB) and triblock (PMOXA-b-PDMS-b-PMOXA, ABA) copolymers. Variation of the molecular weight induces changes in the membrane thickness and thus the fluidity of the membrane. The diffusion of membrane proteins within synthetic triblock copolymer membranes was investigated. The study revealed that the membrane proteins are mobile even at hydrophobic mismatches of up to 7 nm, which is a factor of seven compared to mismatches existing in biological membranes. The advantage of PDMS-containing block copolymers is their enormous flexibility even at high molecular weights, which provides a similar membrane environment compared to biological phospholipid membranes. This explains and displays the ability of PDMS to compress in contact to membrane proteins. Their diffusion decreases steadily with increasing thickness mismatch. The importance of a very flexible polymer for the generation of biomimetic membranes was elucidated for membrane protein insertion, such as PDMS, which offers high fluidity and high membrane stability within membranes with even large thicknesses. The properties of these synthetic membranes investigated here, i.e. fluidity, lateral diffusion and membrane thickness, are important for the generation of biomimetic membranes for technological applications

Tailoring the properties of PECVD deposited terpinen-4ol thin films

Polymer thin films have been of significant research interest in the field of, mechanics, optics, electronics and medicine. Bioactive coatings are extensively used in marine and medical field for the prevention of biofouling which is colonization of any wetted surface by flora and fauna. Fouling of the surfaces has severe implications for the performance of the material and biocide based coating have been used in the prevention of marine fouling. However, these coatings have adverse environmental effects. Natural antifouling products derived from organisms have been found to be an excellent alternative to biocide based strategies. Terpinen-4-ol derived from Australian Tea tree oil has antimicrobial properties. The Plasma enhanced chemical vapor deposition (PECVD) method has been used to develop environmentally friendly antifouling coating from Terpinen-4-ol. The effect of Process variables such as substrate temperature have been investigated on the PECVD of terpinen-4-ol. The influence of surface functionalization and the deposition mode of terpinen-4-ol plasma polymer on its antibacterial property has been studied. Coating created in the form of bilayer are tested for their marine antifouling behavior. The substrate temperature was found to influence the deposition mechanism of Terpinen-4-ol plasma polymers. Hydro Stable terpinen-4-ol plasma polymers were found to be formed at higher substrate temperature. Pulse plasma deposited films exhibited enhanced antibacterial performance. Grafting of ZnO nanoparticles onto the surface of the terpinen-4-ol polymer boosted the antibacterial and UV absorbing properties. The deposited bilayer coatings were effective in preventing the primary stage of marine biofouling. The bilayer acted as biocidal self-polishing coating

Recent Advances in Hybrid Biomimetic Polymer-Based Films: from Assembly to Applications

Biological membranes, in addition to being a cell boundary, can host a variety of proteins that are involved in different biological functions, including selective nutrient transport, signal transduction, inter- and intra-cellular communication, and cell-cell recognition. Due to their extreme complexity, there has been an increasing interest in developing model membrane systems of controlled properties based on combinations of polymers and different biomacromolecules, i.e., polymer-based hybrid films. In this review, we have highlighted recent advances in the development and applications of hybrid biomimetic planar systems based on different polymeric species. We have focused in particular on hybrid films based on (i) polyelectrolytes, (ii) polymer brushes, as well as (iii) tethers and cushions formed from synthetic polymers, and (iv) block copolymers and their combinations with biomacromolecules, such as lipids, proteins, enzymes, biopolymers, and chosen nanoparticles. In this respect, multiple approaches to the synthesis, characterization, and processing of such hybrid films have been presented. The review has further exemplified their bioengineering, biomedical, and environmental applications, in dependence on the composition and properties of the respective hybrids. We believed that this comprehensive review would be of interest to both the specialists in the field of biomimicry as well as persons entering the field

Fabrication of Smart Aqueous Self-Lubricating Icephobic Coatings Containing Encapsulated Phase Change Materials (PCM)

Smart icephobic coatings have attracted much attention owing to their promising application prospects in reducing ice adhesion, decreasing ice nucleation temperature, and delaying freezing time. Such coatings can sense changes in environmental stimuli, such as temperature, humidity, pressure, and pH, and provide an anti-icing or deicing response. These coatings can be categorized into several groups depending on the type of stimuli. In the present thesis, we chose two different smart icephobic strategies to develop novel coatings with enhanced anti-icing and deicing properties. First, aqueous self-lubricating coatings were developed by incorporating the polyethylene glycol (PEG)–polydimethylsiloxane (PDMS) copolymer in an elastomeric matrix. The presence of hydrophilic groups on PEG–PDMS copolymers can contribute to the formation of a quasi-liquid-like layer (QLL) that can improve the icephobic performance of the coatings. Surface analysis of the fabricated coatings confirmed that blending these copolymers into the elastomeric matrix increased the effective contact area between the water droplet and surface. Moreover, increased copolymer content reduced the ice nucleation temperature and prolonged the freezing-delay time. Two different methods, namely, push-off adhesion and centrifugal adhesion tests, were applied to study ice adhesion on the coatings. In general, adding PEG–PDMS copolymer into the PDMS matrix produced an unfrozen lubricating layer, resulting in decreased ice adhesion. Although excessive copolymer content saturated the coating with copolymer, which led to phase separation. Consequently, the surface roughness heightened; therefore, the ice adhesion strength increased owing to the mechanical interlocking between the ice and surface. Second, given the capability of phase change materials (PCMs) to restore and release a large amount of latent heat during the phase change process, we designed a smart icephobic coating by embedding PCM microcapsules into the PDMS coating. For this purpose, a mixture of n-dodecane, n-tetradecane was successfully encapsulated in a poly urea–formaldehyde (PUF) shell via in situ polymerization. Then, the prepared microcapsules were incorporated into PDMS. Differential scanning calorimetry (DSC) confirmed that the PCM mixture preserved its capability of latent heat release while being encapsulated and incorporated within the elastomeric coating. This analysis also showed that the presence of PCM microcapsules reduced the ice nucleation temperature very likely due to the released latent heat. A specially designed apparatus called micro-push-off set-up was used to evaluate the ice adhesion for a short period after complete freezing. The measurement demonstrated that embedding PCM microcapsules can reduce the ice adhesion strength because of the possible scenario of producing QLL or thermal expansion differences. Furthermore, the reduced amount of ice accumulated on the PCM-containing coatings stemmed from the decreased ice adhesion. Finally, we evaluated the synergistic effect of combining the above-mentioned strategies by embedding PCM microcapsules into PEG–PDMS copolymer-containing coatings. A mixture of n-dodecane and n-tetradecane with an optimized ratio was encapsulated within the PUF shell. The obtained microcapsules were embedded into the PDMS coating containing 2.5 wt.% hydroxyl-terminated PEG–PDMS copolymer. With DSC, it was verified that incorporating the PCM microcapsules into the aqueous self-lubricating coating shifted the ice nucleation temperature toward colder temperatures. Evaluation of complete freezing time also supported the DSC results, as freezing time was increased by embedding the PCM microcapsules within the coating. The enhanced anti-icing performance can be related to the latent heat released by PCM, which preserved the QLL for a prolonged period. Moreover, it was observed that the aqueous self-lubricating coating containing PCM microcapsules showed lower ice adhesion strength than the self-lubricating coatings lacking microcapsules, and increased concentrations of the microcapsules resulted in decreased ice adhesion. A lower ice adhesion strength also resulted in a reduction in the amount of ice accumulated on the surface. Combining 10 icing/deicing cycles and micro-push-off test confirmed that no considerable changes in ice adhesion strength occurred over the subsequent deicing events. Therefore, the fabricated coatings can be considered a potential candidate for various icephobic applications. Les revêtements glaciophobes intelligents ont attiré beaucoup d'attention en raison de leurs perspectives d'application prometteuses pour réduire l'adhérence de la glace, abaisser la température et retarder le temps de nucléation de la glace. De tels revêtements peuvent ressentir les changements dans les stimuli environnementaux comme la température, la pression et le pH, et fournir une réponse anti-givrage ou dégivrage. Selon le type de stimuli, ces revêtements peuvent être classés en plusieurs groupes. Dans la présente thèse, nous avons choisi deux stratégies glaciophobes intelligentes différentes pour développer de nouveaux revêtements glaciophobes intelligents aux propriétés anti-givrantes et dégivrantes améliorées. Dans un premier temps, les revêtements autolubrifiants aqueux ont été développés en incorporant le copolymère PEG-PDMS dans une matrice élastomère. La présence des groupes hydrophiles sur les copolymères PEG-PDMS peut contribuer à la formation de la couche quasi liquide (QLL) capable d’améliorer les performances glaçiophobes des revêtements. L'analyse de surface des revêtements fabriqués a confirmé que l’incorporation de ces copolymères dans la matrice élastomère augmentait la surface de contact effective entre la gouttelette d'eau et la surface. De plus, une teneur accrue en copolymère réduit la température de nucléation de la glace et retarde davantage le point de congélation. Deux méthodes différentes d'adhérence, la poussée (push-off) et les tests d'adhérence centrifuge ont été appliquées pour mesure l'adhérence de la glace sur les revêtements. En général, l'ajout de copolymère PEG-PDMS dans la matrice de PDMS produit une couche lubrifiante surfondue, entraînant une diminution de l'adhérence de la glace. Malgré les caractéristiques glaciophobes améliorées grâce à l’ajout de copolymère, une teneur excessive en a saturé le revêtement, ce qui a conduit à la séparation de phase. Par conséquent, la rugosité de la surface s'est accrue donnant lieu à une augmentation de la contrainte d’adhérence de la glace, en raison de l'enclenchement mécanique entre la glace et la surface. Deuxièmement, compte tenu de la capacité des matériaux à changement de phases (PCM) à emmagasiner et à libérer une grande quantité de chaleur latente au cours de leur processus de changement de phase, un revêtement glaciophobe intelligent a été conçu en incorporant des microcapsules de PCM dans un revêtement à base de PDMS. À cette fin, un mélange de PCM a été encapsulé avec succès dans une coque en polyurée-formaldéhyde (PUF) via une polymérisation in situ. Ensuite, les microcapsules préparées ont été incorporées dans la matrice. Le test de calorimétrie à balayage différentiel (DSC) a confirmé que le mélange PCM a conservé sa capacité de dégagement de chaleur latente lorsqu'il est encapsulé et incorporé dans le revêtement élastomère. Cette analyse a également montré que la présence des microcapsules de PCM réduisait la température de nucléation de la glace, très probablement en raison de la chaleur latente dégagée. Un appareil spécialement conçu, appelé configuration micro-push-off, a été utilisé pour évaluer l'adhérence de la glace pendant une courte période après la congélation complète. La mesure a démontré que l'incorporation de microcapsules PCM peut réduire la contrainte d'adhérence de la glace en raison de l'un ou l'autre des scénarios possibles de production de QLL ou de différences de dilatation thermique. De plus, la quantité réduite de glace accumulée sur les revêtements contenant du PCM proviendraient de la diminution de l'adhérence de la glace.Enfin, l'effet synergique de la combinaison des stratégies mentionnées ci-dessus en imprégnant des revêtements contenant du copolymère PEG-PDMS avec des microcapsules PCM a été évalué. Pour commencer, un mélange de n-dodécane et de n-tétradécane avec un rapport optimisé a été encapsulé dans la coque PUF. Les microcapsules obtenues ont été incorporées dans le revêtement PDMS contenant en masse 2,5 % m/m de copolymère PEG-PDMS à terminaison hydroxyle. Le test DSC a prouvé que l'incorporation des microcapsules PCM dans le revêtement autolubrifiant aqueux a déplacé la température de nucléation de la glace vers des températures plus froides. L'évaluation du temps de congélation complet a également confirmé les résultats du DSC, car le temps de congélation a été prolongé avec l’incorporation des microcapsules PCM dans le revêtement. Les performances antigivrantes améliorées peuvent être liées au dégagement de chaleur latente par le PCM qui a préservé la QLL pendant une période plus longue. De plus, il a été observé que le revêtement autolubrifiant aqueux contenant des microcapsules PCM présentait une contrainte d'adhérence à la glace inférieure à celle des revêtements autolubrifiants dépourvus de microcapsules. Aussi, des concentrations accrues de microcapsules diminueraient-elles l'adhérence à la glace. Une plus faible contrainte d'adhérence de la glace a également contribué à une réduction de la quantité de glace accumulée sur la surface. La combinaison de dix cycles de givrage/dégivrage et d'un test de micro-poussée a confirmé qu'il n'y avait pas de changements considérables dans la contrainte d'adhérence de la glace au cours des événements de dégivrage ultérieurs. En somme, les revêtements fabriqués peuvent être considérés comme un candidat potentiel pour diverses applications glaciophobes