A Spontaneous In Situ Thiol-Ene Crosslinking Hydrogel with Thermo-Responsive Mechanical Properties.

The thermo-responsive behavior of Poly(N-isopropylacrylamide) makes it an ideal candidate to easily embed cells and allows the polymer mixture to be injected. However, P(NiPAAm) hydrogels possess minor mechanical properties. To increase the mechanical properties, a covalent bond is introduced into the P(NIPAAm) network through a biocompatible thiol-ene click-reaction by mixing two polymer solutions. Co-polymers with variable thiol or acrylate groups to thermo-responsive co-monomer ratios, ranging from 1% to 10%, were synthesized. Precise control of the crosslink density allowed customization of the hydrogel's mechanical properties to match different tissue stiffness levels. Increasing the temperature of the hydrogel above its transition temperature of 31 °C induced the formation of additional physical interactions. These additional interactions both further increased the stiffness of the material and impacted its relaxation behavior. The developed optimized hydrogels reach stiffnesses more than ten times higher compared to the state of the art using similar polymers. Furthermore, when adding cells to the precursor polymer solutions, homogeneous thermo-responsive hydrogels with good cell viability were created upon mixing. In future work, the influence of the mechanical micro-environment on the cell's behavior can be studied in vitro in a continuous manner by changing the incubation temperature.

Carbon nanotubes as a nitric oxide nano-reservoir improved the controlled release profile in 3D printed biodegradable vascular grafts.

Small diameter vascular grafts (SDVGs) are associated with a high failure rate due to poor endothelialization. The incorporation of a nitric oxide (NO) releasing system improves biocompatibility by using the NO effect to promote endothelial cell (EC) migration and proliferation while preventing bacterial infection. To circumvent the instability of NO donors and to prolong NO releasing, S-nitroso-N-acetyl-D-penicillamine (SNAP) as a NO donor was loaded in multi-walled carbon nanotubes (MWCNTs). Successful loading was confirmed with a maximum SNAP amount of ~ 5% (w/w) by TEM, CHNS analysis and FTIR spectra. SDVGs were 3D printed from polycaprolactone (PCL) and coated with a 1:1 ratio of polyethylene glycol and PCL dopped with different concentrations of SNAP-loaded matrix and combinations of MWCNTs-OH. Coating with 10% (w/w) SNAP-matrix-10% (w/w) SNAP-MWCNT-OH showed a diminished burst release and 18 days of NO release in the range of 0.5-4 × 10-10 mol cm-2 min-1 similar to the NO release from healthy endothelium. NO-releasing SDVGs were cytocompatible, significantly enhanced EC proliferation and migration and diminished bacterial viability. The newly developed SNAP-loaded MWCNT-OH has a great potential to develop NO releasing biomaterials with a prolonged, controlled NO release promoting in-situ endothelialization and tissue integration in vivo, even as an approach towards personalized medicine.

Gastro-resistant encapsulation of amorphous solid dispersions containing darunavir by coaxial electrospraying.

The relatively simple technique of coaxial electrospraying allows to produce core-shell microparticles with potentially high encapsulation efficiencies. In this study, amorphous solid dispersions of a hydroxypropyl methylcellulose or polyvinlypyrrolidone based polymer matrix containing the active pharmaceutical ingredient darunavir were coated with a gastro-resistant shell polymer that does not dissolve at lower pH present in the stomach, but only later at a higher pH in the small intestine. A multitude of shell polymers were tested with the aim to identify a material that limits the drug release to less than 10% after two hours at a pH of 1 to comply with the European Pharmacopoeia regarding gastro-resistant formulations. In parallel, the core-shell structure of the particles was determined with confocal imaging and their surface morphology with SEM imaging. While the structural analysis revealed significant differences between the different formulations, all investigated shell polymers exhibited a burst drug release followed by a slow release for the remainder of a two hour period. Ultimately, the shell copolymer poly(methacrylic acid-co-methyl methacrylate), in particular for a monomer ratio 1/2, resulted consistently in darunavir release below the 10% upper limit compared to the other tested polymers, where such low releases were inaccessible. Further investigation of this shell polymer revealed that both the monomer ratio of methacrylic acid to methyl methacrylate in the copolymer and the utilized solvent are determining factors in the release performance of the final particles.

Synthesis and post-functionalization of alternate-linked-meta-para-[2 n .1 n ]thiacyclophanes.

In recent decades, considerable research attention has been devoted to new synthetic procedures for thiacyclophanes. Thiacyclophanes are widely used as host molecules for the molecular recognition of organic compounds as well as metals. Herein, we report the selective and high-yielding synthesis of novel alternate-linked-meta-para-thiacyclophanes. These novel thiacyclophanes are selectively synthesized in high-yielding procedures. Furthermore, post-functionalization of the phenolic moieties was successfully performed. The 3D structure of the alternate-linked-meta-para-[22.12]thiacyclophane was further elucidated via X-ray crystallographic analysis.

Saturation reduces in-vitro leakage of monomers from composites.

OBJECTIVE: Accurate knowledge of the quantity of released monomers from composites is important. To evaluate the elution of monomers, polymerized composites are typically immersed in an extraction solvent. The objective was to determine whether the volume of extraction solvent and the immersion time influences monomer leachability from dental composite materials. METHODS: Composite disks of two commercial composites, (Filtek Supreme XTE, 3M ESPE and G-aenial Universal Flo, GC) were prepared. The disks (n=10) were placed in a glass vial with 1ml, 2ml or 3ml of extraction solvent (100% ethanol with deuterated diethylphalate as internal standard). After either 7 or 30 days at 37°C, the supernatant was collected and the amount of released monomers (BisEMA, BisGMA, UDMA, TEGDMA) and bisphenol A was measured with liquid chromatography mass spectroscopy. RESULTS: For both tested composites, the highest amount of released monomers was measured after sample incubation in 3ml, while the lowest amount was measured in 1ml of extraction solvent. Furthermore, 30 days did not result in much more monomer release compared to 7 days, and for most monomers, there was no statistically significant difference in release between 7 and 30 days. SIGNIFICANCE: Release kinetics in in-vitro experiments are also influenced by saturation of the extraction solvent with the leached monomers. This is important as it is unlikely that saturation can be reached in an in-vivo situation, where saliva (or pulpal fluid) is continuously refreshed. Saturation of the extraction solvent can be avoided in-vitro by refreshing the extraction medium after equal time intervals.

Stable star polymer nanolayers and their thermoresponsiveness as a tool for controlled culture and detachment of fibroblast sheets.

In this study, we describe novel thermoresponsive star copolymer surfaces used for the first time for the culture of fibroblast sheets, followed by their detachment, controlled by a change in temperature. To date, no star polymers, or their layers, have been used for this purpose. A "grafting to" strategy was applied to obtain poly[oligo(ethylene glycol) methacrylate] star layers on functionalized solid supports. Atom transfer radical polymerization of oligo(ethylene glycol) methacrylates and glycidyl methacrylate initiated with modified poly(arylene oxindole) yielded stars with molar masses up to Mn = 380 000 g mol-1. Stars were attached to a glass substrate via the reaction between the functional epoxy groups of the stars with the amine groups of the functionalized substrate. The thickness of the layer was related to the dimensions of isolated stars in solution, which showed that multilayers were obtained. Above the phase transition temperature, polymer nanolayers were hydrophobic, thus enabling the growth of fibroblasts on their surfaces and the formation of a cell sheet. Decreasing the temperature below the phase transition temperature made the star surfaces hydrophilic. This eliminated the affinity of the surface for cells and led to detachment of the intact fibroblast sheet. These observations have shown for the first time that the star polymer architecture favors the detachment of cell sheets as compared to linear polymer analogues grafted onto supports, thus reducing the time of this process. Knowledge of the influence of the polymer topology on layer properties and cell growth and detachment can aid in the development of polymeric materials for tissue culture applications.

Synthesis, Characterization and Cytotoxicity of Novel Thermoresponsive Star Copolymers of N,N'-Dimethylaminoethyl Methacrylate and Hydroxyl-Bearing Oligo(Ethylene Glycol) Methacrylate.

Novel, nontoxic star copolymers of N,N-dimethylaminoethyl methacrylate (DMAEMA) and hydroxyl-bearing oligo(ethylene glycol) methacrylate (OEGMA-OH) were synthesized via atom transfer radical polymerization (ATRP) using hyperbranched poly(arylene oxindole) as the macroinitiator. Stars with molar masses from 100,000 g/mol to 257,000 g/mol and with various amounts of OEGMA-OH in the arms were prepared. As these polymers can find applications, e.g., as carriers of nucleic acids, drugs or antibacterial or antifouling agents, in this work, much attention has been devoted to exploring their solution behavior and their stimuli-responsive properties. The behavior of the stars was studied in aqueous solutions under various pH and temperature conditions, as well as in PBS buffer, in Dulbecco's modified Eagle's medium (DMEM) and in organic solvents for comparison. The results indicated that increasing the content of hydrophilic OEGMA-OH units in the arms up to 10 mol% increased the cloud point temperature. For the stars with an OEGMA-OH content of 10 mol%, the thermo- and pH-responsivity was switched off. Since cytotoxicity experiments have shown that the obtained stars are less toxic than homopolymer DMAEMA stars, the presented studies confirmed that the prepared polymers are great candidates for the design of various nanosystems for biomedical applications.

Acid-Sensitive BODIPY Dyes: Synthesis through Pd-Catalyzed Direct C(sp3 )-H Arylation and Photophysics.

A novel palladium-catalyzed direct C(sp3 )-H arylation of the methyl group at the 8-position of BODIPY by bromoarenes was established. A deprotonative cross-coupling process was supposed to be involved in the reaction. This approach allowed us to attach electron-donating/withdrawing, halogen substituted aryls and a heteroaryl with a yield running from 55 to 99 %. Novel pH sensors, which in the absence of acid showed the occurrence of photoinduced electron transfer, were synthesized by attaching dimethylaniline to the methyl at the C8-position of BODIPY. The reference compounds with dimethylaniline directly attached to the C8-position were also synthesized and besides photoinduced electron transfer also showed a charge-transfer emission. Their photophysical properties were investigated by steady-state fluorescence, time-correlated single-photon counting and femtosecond fluorescence up-conversion. Time-dependent density functional (TD-DFT) electronic-structure calculations on the properties of the excited states corresponding to local excitation of the BODIPY core and to charge transfer were conducted. Upon addition of trifluoroacetic acid in toluene and ethanol, the partial fluorescence intensity recovery was at least an order of magnitude more efficient with the newly synthesized sensors compared to the traditional reference sensors. The improved sensitivity of these novel BODIPY-based pH sensors was attributed to less efficient proton-coupled electron transfer of the protonated species.

Simultaneous analysis of bisphenol A based compounds and other monomers leaching from resin-based dental materials by UHPLC-MS/MS.

Resin-based dental materials have raised debates concerning their safety and biocompatibility, resulting in a growing necessity of profound knowledge on the quantity of released compounds into the oral cavity. In this context, the aim of this study was to develop a comprehensive and reliable procedure based on liquid chromatography with mass spectrometry for the simultaneous analysis of various leached compounds (including bisphenol A based compounds) in samples from in vitro experiments. Different experiments were performed to determine the optimal analytical parameters, comprising mass spectrometry parameters, chromatographic separation conditions, and sample preparation. Four internal standards were used as follows: deuterated diethyl phthalate and bisphenol A (commercially available), and deuterated analogues of triethylene glycol dimethacrylate and urethane dimethacrylate (custom-made). The optimized method was validated for linearity of the calibration curves and the associated correlation coefficient, lower limit of quantification, higher limit of quantification, and intra- and interassay accuracy and precision. Additionally, the developed liquid chromatography with tandem mass spectrometry method was applied to the analysis of leaching compounds from four resin-based dental materials. The results indicated that this method is suitable for the analysis of different target compounds leaching from dental materials. This method might serve as a valuable basis for quick and accurate quantification of leached compounds from resin-based dental materials in biological samples.

Water-soluble sulfonated hyperbranched poly(arylene oxindole) catalysts as functional biomimics of cellulases.

A new polymer acid catalyst, sulfonated hyperbranched poly(arylene oxindole), 5-OH-SHPAO, was prepared for selective cellulose hydrolysis. Its superior catalysis, showing high glucose selectivity at almost full cellulose conversion, is attributed to the presence of an hydroxyl group next to the sulfonic acid, therefore mimicking the separate acid-base pair in the cellulase active site.

Poly(alanine): Structure and Stability of the D and L-Enantiomers.

High-performance, biobased materials can potentially be manufactured from polymerized α-amino acids (α-polypeptides). This paper reports on the synthesis, structure, and properties of both polyalanine enantiomers (PLAla and PDAla). The molecular structure of the polypeptide chains, their molecular weight, and polydispersity were investigated by (1)H NMR, MALDI-TOF, and size-exclusion chromatography. The secondary structure and crystalline order were probed via Fourier transform infrared spectroscopy, circular dichroism, and (synchrotron) wide-angle X-ray diffraction. The phase behavior and thermal stability were assessed by differential scanning calorimetry and thermogravimetric analysis. The kinetically trapped PAla chain conformation in the solid state, after synthesis or solvent treatments, is the α-helical shape. Upon heating, crystals from the α-helices convert into more stable crystals from ß-sheets at a temperature higher than 210 °C. This temperature is close to where polymer degradation sets in. The ß-sheet crystals combine melting with thermal degradation at temperatures above 330 °C. In the presence of superheated water, the conversion from α-helices to ß-sheets happens at lower temperatures, allowing for a conversion without degradation.

Homodiselenacalix[4]arenes: Molecules with Unique Channelled Crystal Structures.

A synthetic route towards homodiselenacalix[4]arene macrocycles is presented, based on the dynamic covalent chemistry of diselenides. The calixarene inner rim is decorated with either alkoxy or tert-butyl ester groups. Single-crystal X-ray analysis of two THF solvates with methoxy and ethoxy substituents reveals the high similarity of their molecular structures and alterations on the supramolecular level. In both crystal structures, solvent channels are present and differ in both shape and capacity. Furthermore, the methoxy-substituted macrocycle undergoes a single-crystal-to-single-crystal transformation during which the molecular structure changes its conformation from 1,3-alternate (loaded with THF/water) to 1,2-alternate (apohost form). Molecular modelling techniques were applied to explore the conformational and energetic behaviour of the macrocycles.

Selenium-Platinum Coordination Dendrimers with Controlled Anti-Cancer Activity.

Dendrimers are considered as good vectors for drug delivery in cancer treatment. However, most anticancer drugs are conjugated to the peripheral surface of dendrimers, sacrificing the advantages of monodispersity and stability belonging to dendrimers. Furthermore, dendrimers in current studies of cancer treatment are mostly used as vectors for drugs, whereas the anticancer activity of dendrimers on their own is less studied. Here we have prepared monodisperse selenium-platinum coordination dendrimers with a selenium-platinum core buried inside. Structures of the dendrimers were determined by various characterizations. The coordination dendrimers showed controlled anticancer activity by themselves, without loading additional drugs. The in vivo study further demonstrated their anticancer activity and low toxicity to normal tissues.

Nonviral Plasmid DNA Carriers Based on N,N'-Dimethylaminoethyl Methacrylate and Di(ethylene glycol) Methyl Ether Methacrylate Star Copolymers.

Star polymers with random and block copolymer arms made of cationic N,N'-dimethylaminoethyl methacrylate (DMAEMA) and nonionic di(ethylene glycol) methyl ether methacrylate (DEGMA) were synthesized via atom transfer radical polymerization (ATRP) and used for the delivery of plasmid DNA in gene therapy. All stars were able to form polyplexes with plasmid DNA. The structure and size of the polyplexes were precisely determined using light scattering and cryo-TEM microscopy. The hydrodynamic radius of a complex of DNA with star was dependent on the architecture of the star arms, the DEGMA content and the number of amino groups in the star compared to the number of phosphate groups of the nucleic acid (N/P ratio). The smallest polyplexes (Rh90°âˆ¼50 nm) with positive zeta potentials (∼15 mV) were formed of stars with N/P=6. The introduction of DEGMA into the star structure caused a decrease of polyplex cytotoxicity in comparison to DMAEMA homopolymer stars. The overall transfection efficiency using HT-1080 cells showed that the studied systems are prospective gene delivery agents. The most promising results were obtained for stars with random copolymer arms of high DEGMA content.

Highly efficient hyperbranched CNT surfactants: influence of molar mass and functionalization.

End-group-functionalized hyperbranched polymers were synthesized to act as a carbon nanotube (CNT) surfactant in aqueous solutions. Variation of the percentage of triphenylmethyl (trityl) functionalization and of the molar mass of the hyperbranched polyglycerol (PG) core resulted in the highest measured surfactant efficiency for a 5000 g/mol PG with 5.6% of the available hydroxyl end-groups replaced by trityl functions, as shown by UV-vis measurements. Semiempirical model calculations suggest an even higher efficiency for PG5000 with 2.5% functionalization and maximal molecule specific efficiency in general at low degrees of functionalization. Addition of trityl groups increases the surfactant-nanotube interactions in comparison to unfunctionalized PG because of π-π stacking interactions. However, at higher functionalization degrees mutual interactions between trityl groups come into play, decreasing the surfactant efficiency, while lack of water solubility becomes an issue at very high functionalization degrees. Low molar mass surfactants are less efficient compared to higher molar mass species most likely because the higher bulkiness of the latter allows for a better CNT separation and stabilization. The most efficient surfactant studied allowed dispersing 2.85 mg of CNT in 20 mL with as little as 1 mg of surfactant. These dispersions, remaining stable for at least 2 months, were mainly composed of individual CNTs as revealed by electron microscopy.

Importance of thiol-functionalized molecules for the structure and properties of compression-molded glassy wheat gluten bioplastics.

High-temperature compression molding of wheat gluten at low water levels yields a rigid plastic-like material. We performed a systematic study to determine the effect of additives with multiple thiol (SH) groups on gluten network formation during processing and investigate the impact of the resulting gluten network on the mechanical properties of the glassy end product. To this end, a fraction of the hydroxyl groups of different polyols was converted into SH functionalities by esterifying with 3-mercaptopropionic acid (MPA). The monofunctional additive MPA was evaluated as well. During low-temperature mixing SH-containing additives decreased the gluten molecular weight, whereas protein cross-linking occurred during high-temperature compression molding. The extent of both processes depended on the molecular architecture of the additives and their concentration. After molding, the material strength and failure strain increased without affecting the modulus, provided the additive concentration was low. The strength decreased again at too high concentrations for polyols with low SH functionalization. Attributing these effects solely to the interplay of plasticization and the SH-facilitated introduction of cross-links is inadequate, since an improvement in both strength and failure strain was also observed in the presence of high levels of MPA. It is hypothesized that, regardless of the molecular structure of the additive, the presence of SH-containing groups induces conformational changes which contribute to the mechanical properties of glassy gluten materials.

Impact of acid and alkaline pretreatments on the molecular network of wheat gluten and on the mechanical properties of compression-molded glassy wheat gluten bioplastics.

Wheat gluten can be converted into rigid biobased materials by high-temperature compression molding at low moisture contents. During molding, a cross-linked protein network is formed. This study investigated the effect of mixing gluten with acid/alkali in 70% ethanol at ambient temperature for 16 h followed by ethanol removal, freeze-drying, and compression molding at 130 and 150 °C on network formation and on types of cross-links formed. Alkaline pretreatment (0-100 mmol/L sodium hydroxide or 25 mmol/L potassium hydroxide) strongly affected gluten cross-linking, whereas acid pretreatment (0-25 mmol/L sulfuric acid or 25 mmol/L hydrochloric acid) had limited effect on the gluten network. Molded alkaline-treated gluten showed enhanced cross-linking but also degradation when treated with high alkali concentrations, whereas acid treatment reduced gluten cross-linking. ß-Elimination of cystine and lanthionine formation occurred more pronouncedly at higher alkali concentrations. In contrast, formation of disulfide and nondisulfide cross-links during molding was hindered in acid-pretreated gluten. Bioplastic strength was higher for alkali than for acid-pretreated samples, whereas the flexural modulus was only slightly affected by either alkaline or acid pretreatment. Apparently, the ratio of disulfide to nondisulfide cross-links did not affect the mechanical properties of rigid gluten materials.

Selenium/Tellurium-Containing Hyperbranched Polymers: Effect of Molecular Weight and Degree of Branching on Glutathione Peroxidase-Like Activity.

A series of novel hyperbranched polyselenides and polytellurides with multiple catalytic sites at the branching units has been synthesized via the polycondensation of A2 + B3 monomers. The GPx-like activities of these polymer mimics were assessed and it was found that the polytellurides showed higher GPx-like activities than the corresponding polyselenides. Interestingly, the polymers with higher molecular weights and degree of branching (DB) showed higher GPx-like activities than the analogous lower molecular weight polymer. The enhancement in the catalytical activity of the hyperbranched polymers with increasing molecular weight affirmed the importance of the incorporation of multiple catalytic groups in the macromolecule which increases the local concentration of catalytic sites.

Homoselenacalix[4]arenes: synthetic exploration and metallosupramolecular chemistry.

Homoselenacalix[4]arenes were synthesized by a [2 + 2] reductive coupling protocol favouring the cyclotetramers. The inner and outer-rim decoration was varied and a bicyclic derivative was prepared by a similar one-pot procedure. Conformational analysis in solution and the solid state showed noticeable differences between the homoselenacalix[4]arenes and the analogous homothiacalix[4]arenes and provided insight into the metal binding potential of the Se-bridged macrocycles. The homoselenacalix[4]arenes were found to bind Ag(I). Complexation was visualized in the solid state and different packing networks were formed depending on the counter ions applied.