Photolithographically Patterned Cell-Repellent PEG-b-PTHPMA Diblock Copolymer for Guided Cell Adhesion and Growth.

Surfaces for guided cell adhesion and growth are indispensable in several diagnostic and therapeutic applications. Towards this direction, four diblock copolymers comprising polyethylene glycol (PEG) and poly(2-tetrahydropyranyl methacrylate) (PTHPMA) are synthesized employing PEG macroinitiators of different chain lengths. The copolymer with a 5000 Da PEG block and a PEG-PTHPMA comonomers weight ratio of 43-57 provides a film with the highest stability in the culture medium and the strongest cell repellent properties. This copolymer is used to develop a positive photolithographic material and create stripe patterns onto silicon substrates. The highest selectivity regarding smooth muscle cell adhesion and growth and the highest fidelity of adhered cells for up to 3 days in culture is achieved for stripe patterns with widths between 25 and 27.5 µm. Smooth muscle cells cultured on such patterned substrates exhibit a decrease in their proliferation rate and nucleus area and an increase in their major axis length, compared to the cells cultured onto non-patterned substrates. These alterations are indicative of the adoption of a contractile rather than a synthetic phenotype of the smooth muscle cells grown onto the patterned substrates and demonstrate the potential of the novel photolithographic material and patterning method for guided cell adhesion and growth.

Responsive Quaternized PDMAEMA Copolymers with Antimicrobial Action.

In this work, the antimicrobial action of partially quaternized poly(2-(dimethylamino)ethyl methacrylate) (PQDMAEMA) copolymers using different alkyl halides is presented. The poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) homopolymer was synthesized by group transfer polymerization, followed by the modification of its tertiary amine groups, using bromoethane, iodoethane, bromohexane and bromoethanol, to introduce permanent cationic, quaternary ammonium salt moieties, randomly distributed along the polymer chains. In all cases, the degree of quaternization was low, at ~10 mol%, as verified by proton nuclear magnetic resonance spectroscopy to preserve the thermo-responsive character of the PDMAEMA precursor polymer. The biocidal activity of the lightly quaternized PQDMAEMA copolymers against Escherichia coli and Staphylococcus aureus was evaluated by calculating the minimum inhibitory concentration (MIC) as well as the minimum bactericidal concentration (MBC) of the polymers and by comparing them to the respective values of the precursor non-quaternized PDMAEMA homopolymer. The antibacterial mechanism of action in the solution was studied by zeta potential measurements, scanning electron microscopy and protein leakage tests signifying the disruption of the outer membrane of the bacterial cells to release their periplasmic proteins.

Antimicrobial Hybrid Coatings Combining Enhanced Biocidal Activity under Visible-Light Irradiation with Stimuli-Renewable Properties.

Hybrid, organic-inorganic, biocidal films exhibiting polishing properties were developed as effective long-lasting antimicrobial surface coatings. The films were prepared using cationically modified chitosan, synthesized by the reaction with 3-bromo-N,N,N-trimethylpropan-1-aminium bromide, to introduce permanent biocidal quaternary ammonium salt (QAS) groups along the polymer backbone and were cross-linked by a novel, pH-cleavable acetal cross-linker, which allowed polishing the hybrid coatings with the solution pH. TiO2 nanoparticles, modified with reduced graphene oxide (rGO) sheets, to narrow their band gap energy value and shift their photocatalytic activity in the visible light regime, were introduced within the polymer film to enhance its antibacterial activity. The hybrid coatings exhibited an effective biocidal activity in the dark (∼2 Log and ∼3 Log reduction for Gram-negative and Gram-positive bacteria, respectively), when only the QAS sites interacted with the bacteria membrane, and an excellent biocidal action upon visible-light irradiation (∼5 Log and ∼6 Log reduction for Gram-negative and Gram-positive bacteria, respectively) due to the synergistic antimicrobial effect of the QAS moieties and the rGO-modified TiO2 nanoparticles. The gradual decrease in the film thickness, upon immersion of the coatings in mildly basic (pH 8), neutral (pH 7), and acidic (pH 6) media, reaching 10, 20, and 70% reduction, respectively, after 60 days of immersion time, confirmed the polishing behavior of the films, whereas their effective antimicrobial action was retained. The biocompatibility of the hybrid films was verified in human cell culture studies. The proposed approach enables the facile development of highly functional coatings, combining biocompatibility and bactericidal action with a "kill and self-clean" mechanism that allows the regeneration of the outer surface of the coating leading to a strong and prolonged antimicrobial action.

High Sensitivity Resists for EUV Lithography: A Review of Material Design Strategies and Performance Results.

The need for decreasing semiconductor device critical dimensions at feature sizes below the 20 nm resolution limit has led the semiconductor industry to adopt extreme ultra violet (EUV) lithography with exposure at 13.5 nm as the main next generation lithographic technology. The broad consensus on this direction has triggered a dramatic increase of interest on resist materials of high sensitivity especially designed for use in the EUV spectral region in order to meet the strict requirements needed for overcoming the source brightness issues and securing the cost efficiency of the technology. To this direction both fundamental studies on the radiation induced chemistry in this spectral area and a plethora of new ideas targeting at the design of new highly sensitive and top performing resists have been proposed. Besides the traditional areas of acid-catalyzed chemically amplified resists and the resists based on polymer backbone breaking new unconventional ideas have been proposed based on the insertion of metal compounds or compounds of other highly absorbing at EUV atoms in the resist formulations. These last developments are reviewed here. Since the effort targets to a new understanding of electron-induced chemical reactions that dominate the resist performance in this region these last developments may lead to unprecedented changes in lithographic technology but can also strongly affect other scientific areas where electron-induced chemistry plays a critical role.

Film Properties and Antimicrobial Efficacy of Quaternized PDMAEMA Brushes: Short vs Long Alkyl Chain Length.

Quaternized poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes bearing quaternary ammonium groups of different alkyl chain lengths (ACLs) were prepared and assessed as biocidal coatings. For the synthesis of the antimicrobial brushes, first well-defined PDMAEMA chains were grown by surface-initiated atom transfer radical polymerization on glass and silicon substrates. Next, the tertiary amine groups of the polymer brushes were modified via a quaternization reaction, using alkyl halides, to obtain the cationic polymers. The polymer films were characterized by Fourier-transform infrared spectroscopy, ellipsometry, atomic force microscopy, and water contact angle measurements. The effect of the ACL of the quaternary ammonium groups on the physicochemical properties of the films as well as the contact killing efficiency of the surfaces against representative Gram-positive and Gram-negative bacteria was investigated. A hydrophilic to hydrophobic transition of the surfaces and a significant decrease of the degree of quaternization of the DMAEMA moieties was found upon increasing the ACL of the quaternization agent above six carbon atoms, allowing the wettability, the thickness, and the pH-response of the brushes to be tuned via a facile postpolymerization, quaternization reaction. At the same time, antimicrobial tests revealed that the hydrophilic polymer brushes exhibited enhanced bactericidal activity against Escherichia coli and Bacillus cereus, whereas the hydrophobic surfaces showed a significant deterioration of the in vitro bactericidal performance. Our results elucidate the antimicrobial action of quaternized polymer brushes, dictating the appropriate choice of the ACL of the quaternization agent for the development of coatings that effectively inhibit biofilm formation on surfaces.

A facile route towards PDMAEMA homopolymer amphiphiles.

Well-defined poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) has been modified at low degrees of quaternization of the tertiary amine groups using alkyl halides with long alkyl chains as the quaternization agents. The resulting PDMAEMA-co-PQDMAEMA copolymers were studied in aqueous solution using potentiometric titrations, turbidimetry, surface tensiometry, dynamic light scattering and zeta potential measurements. An increase of the hydrophilicity of the precursor polymer, leading to an increase or even elimination of the lower critical solution temperature (LCST) for the quaternized copolymers was found; this extended the temperature range of the stable polymer solution. At the same time, it was shown that the hydrophobic character of the polymer increases upon quaternization, leading to higher surface activity compared to the precursor PDMAEMA homopolymer, and, thus, to more effective polymeric surfactants. This contradiction in the copolymer behavior was attributed to the interplay between the polymer self-assembly in the aqueous medium and the polymer adsorption at the air/water interface, which dominate the cloud point and the surface properties, respectively.

Harnessing photochemical internalization with dual degradable nanoparticles for combinatorial photo-chemotherapy.

Light-controlled drug delivery systems constitute an appealing means to direct and confine drug release spatiotemporally at the site of interest with high specificity. However, the utilization of light-activatable systems is hampered by the lack of suitable drug carriers that respond sharply to visible light stimuli at clinically relevant wavelengths. Here, a new class of self-assembling, photo- and pH-degradable polymers of the polyacetal family is reported, which is combined with photochemical internalization to control the intracellular trafficking and release of anticancer compounds. The polymers are synthesized by simple and scalable chemistries and exhibit remarkably low photolysis rates at tunable wavelengths over a large range of the spectrum up to the visible and near infrared regime. The combinational pH and light mediated degradation facilitates increased therapeutic potency and specificity against model cancer cell lines in vitro. Increased cell death is achieved by the synergistic activity of nanoparticle-loaded anticancer compounds and reactive oxygen species accumulation in the cytosol by simultaneous activation of porphyrin molecules and particle photolysis.

Photodegradable polymers for biotechnological applications.

Photodegradable polymers constitute an emerging class of materials that finds numerous applications in biotechnology, biomedicine, and nanoscience. This article highlights some of the emerging applications of photodegradable polymers in the form of homopolymers, particles and self-assembled constructs in solution, hydrogels for tissue engineering, and photolabile polymers for biopatterning applications. Novel photochemistries have been combined with controlled polymerization methods, which result in well-defined photodegradable materials that exhibit light mediated and often controlled fragmentation processes.