Luminita Cianga

Review paper: Progress in the Field of Conducting Polymers for Tissue Engineering Applications

This review focuses on one of the most exciting applications area of conjugated conducting polymers, which is tissue engineering. Strategies used for the biocompatibility improvement of this class of polymers (including biomolecules’ entrapment or covalent grafting) and also the integrated novel technologies for smart scaffolds generation such as micropatterning, electrospinning, self-assembling are emphasized. These processing alternatives afford the electroconducting polymers nanostructures, the most appropriate forms of the materials that closely mimic the critical features of the natural extracellular matrix. Due to their capability to electronically control a range of physical and chemical properties, conducting polymers such as polyaniline, polypyrrole, and polythiophene and/or their derivatives and composites provide compatible substrates which promote cell growth, adhesion, and proliferation at the polymer—tissue interface through electrical stimulation. The activities of different types of cells on these materials are also presented in detail. Specific cell responses depend on polymers surface characteristics like roughness, surface free energy, topography, chemistry, charge, and other properties as electrical conductivity or mechanical actuation, which depend on the employed synthesis conditions. The biological functions of cells can be dramatically enhanced by biomaterials with controlled organizations at the nanometer scale and in the case of conducting polymers, by the electrical stimulation. The advantages of using biocompatible nanostructures of conducting polymers (nanofibers, nanotubes, nanoparticles, and nanofilaments) in tissue engineering are also highlighted.

Hybrid materials consisting of an all-conjugated polythiophene backbone and grafted hydrophilic poly(ethylene glycol) chains

Organic hybrid materials consisting of an all-conjugated polythiophene backbone and well-defined poly(ethylene glycol) (PEG) grafted chains have been prepared by anodic polymerization of chemically synthesized macromonomers. The latter consist of a pentathiophene sequence in which the central ring bears a PEG chain with Mw = 1000 or 2000 at the 3-position. The influence of the polymerization potential, the length of the PEG branches and the dopant agent on the structure and properties of the graft copolymers has been examined. The chemical structure of the grafted materials has been corroborated by FTIR and X-ray photoelectron spectroscopies. Scanning electron microscopy and atomic force microscopy studies reveal that the morphology and topography of these materials are influenced by the above mentioned factors, even though homogeneous films showing a compact distribution of nanoaggregates, very flat surfaces (i.e. roughness < 15 A) and nanometric thickness (i.e. 100–500 nm) were obtained in all cases. Cyclic voltammetry assays have been used to determine the presence of charged species, the electroactivity, the electrostability and the formation of cross-links. The electrochemical stability of the copolymer with grafted PEG chains of Mw = 1000 has been found to increase with the number of consecutive oxidation–reduction cycles (self-electrostabilizing behavior). Finally, a preliminary investigation into the applicability of these hybrid materials as active surfaces for the selective adsorption of proteins is presented.

Polythiophene-g-poly(ethylene glycol) graft copolymers for electroactive scaffolds

The properties, microscopic organization and behavior as the cellular matrix of an all-conjugated polythiophene backbone (PTh) and well-defined poly(ethylene glycol) (PEG) grafted chains have been investigated using different experimental techniques and molecular dynamic simulations. UV-vis spectroscopy has been used to determine the optical band gap, which has been found to vary between 2.25 and 2.9 eV depending on the length of the PEG chains and the chemical nature of the dopant anion, and to detect polaron → bipolaron transitions between band gap states. The two graft copolymers have been found to be excellent cellular matrices, their behavior being remarkably better than that found for other biocompatible polythiophene derivatives [e.g. poly(3,4-ethylenedioxythiophene)]. This is fully consistent with the hydrophilicity of the copolymers, which increases with the molecular weight of the PEG chains, and the molecular organization predicted by atomistic molecular dynamics simulations. Graft copolymers tethered to the surface tend to form biphasic structures in solvated environments (i.e. extended PTh and PEG fragments are perpendicular and parallel to the surface, respectively) while they collapse onto the surface in desolvated environments. Furthermore, the electrochemical activity and the maximum of current density are remarkably higher for samples coated with cells than for uncoated samples, suggesting multiple biotechnological applications in which the transmission with cells is carried out at the electrochemical level.

Fluorescent micellar nanoparticles by self-assembly of amphiphilic, nonionic and water self-dispersible polythiophenes with “hairy rod” architecture

Polymers with “hairy-rod” architecture having oligo/polythiophene (PTh) as main chain and poly (ethylene glycol) (PEG) (Mn = 2000) as flexible side chains were obtained by combining the “macromonomer technique” with specific methods for the synthesis of conjugated polymers. Fluorescent nanoparticles of core–shell type with high colloidal stability were obtained from these water self-dispersible materials by a direct dissolution method in aqueous media. It has been shown that the size and photophysical properties of the micellar nanoparticles in aqueous dispersions as well as the bulk properties of the investigated materials can be tuned by varying the PEG side chain density and by the modality of PEG connection to the PTh main chains. The presence of the PEG shells in the structure of these fluorescent nanoparticles cans suppress the non-specific interactions with biomolecules on the one side and on the other side they work as a biomimetic interface that could facilitate their potential use as cell-imaging agents. The present attempt offers an ease of access alternative to conducting polymer nanoparticle encapsulation in a biocompatible matrix by nanoprecipitation.

Electroactive and bioactive films of random copolymers containing terthiophene, carboxyl and Schiff base functionalities in the main chain

A new bis-thienyl type monomer with preformed azomethine linkages (AzbT) was chemically synthesized and, subsequently, electro-copolymerized with 2,2′ : 5′,2′′-terthiophene (Th3). AzbT : Th3 mixtures with different molar ratios (i.e. 50 : 50, 60 : 40 and 80 : 20) were considered, the resulting thin films being made of random insoluble copolymers, P(AzbT-co-Th3)s. The content of AzbT in P(AzbT-co-Th3)s was found to increase with the AzbT : Th3 molar ratio in the electropolymerization medium. Furthermore, characterization of the different copolymers suggests the existence of several concomitant processes in the reaction medium. Thus, depending on the composition of the reaction medium, AzbT worked as a co-monomer and/or as a dopant for the growing polymer chains. The morphology of the films evolved from a porous multi-level surface to a more compact and flat globular structure with increasing AzbT content. On the other hand, the electrochemical and optical properties were also influenced by the AzbT : Th3 ratio. Cytotoxicity and cell adhesion and proliferation tests, which were performed using human osteosarcoma and monkey kidney epithelial cell lines (MG-63 and Vero, respectively), revealed that P(AzbT-co-Th3) matrices can be potentially applied as bioactive substrates. This behaviour was especially relevant for the 80 : 20 copolymer, which exhibits optical and electrochemical properties in the range of polythiophene derivatives, suggesting that it is a promising functional biomaterial.

Conducting Copolymers of Thiophene-Functionalized Polystyrene

The syntheses of conducting copolymers of thiophene-functionalized polystyrene and pyrrole (PS/PPy) were achieved using p-toluene sulfonic acid (PTSA) as the supporting electrolyte via constant potential electrolysis technique. Characterization of the samples was performed by a combination of techniques: cyclic voltammetry (CV), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), NMR, and FT-IR analyses. The conductivities were measured by the four-probe technique.

Synthesis and self-assembly of fluorene-vinylene alternating copolymers in “Hairy-Rod” architecture: side chain – mediated tuning of conformation, microstructure and photophysical properties

Abstract In the present work, we demonstrate that the side chain choice, as a tunable parameter, is an effective strategy to drive molecular ordering, packing motifs and overall microstructure of a conjugated polymer. By applying Wittig polycondensation novel ‘rod-coil’ structures, in ‘hairy-rod’ architecture, based on fluorenylene vinylene copolymers with well-defined oligomeric side chains were synthesized using ‘T’-shaped or ‘Cross’-shaped p-terphenyl macromonomers. The overall character of the copolymers was systematically varied by attaching of hydrophilic PEG 2000, hydrophobic polar oligo-ε-caprolactone or hydrophobic and non-polar oligostyrene side chains. Self-assembling of the copolymers by simple direct dissolution method was achieved in various solvents by modifying their selectivity in relation to the side chain or main chain. The morphology investigations demonstrated that unique nanofeatures obtained in each case (helical foldamers, vesicles, disks, or helical turns) depend on the nature, number, and position of the side chains which influence the photophysical properties. The ‘hairy-rod’ topology is also responsible for the self-assembly of the materials in molten state, as thermal analysis revealed, and the propensity of the new synthesized conjugated main chain for helical folding was evidenced, as well.

Synthesis and Characterization of Fluorescent, Nonionic, Water Self-Dispersible Oligothiophenes

Two α-septithiophenes substituted at the third position of the middle ring with polyethyleneglycol of different molecular weights (PEG 1000 and PEG 2000) were synthesized using Suzuki condensation. Their structural characterization was performed by 1H NMR and FT-IR. The thermal behavior of the new synthesized oligothiophenes was investigated by differential scanning calorimetry (DSC) and thermogravimetrical (TGA) analysis. Photophysical properties in solutions were evaluated by UV-vis and fluorescence measurements using different solvents. The amphiphilic nature of the synthesized oligothiophenes and the presence of the PEG side chains induced self-dispersibility in water and the possibility of fluorescent nanoparticles forming by self-assembling. The size of nanoparticles in water was assessed by DLS and AFM investigations.

The biocompatible polythiophene-g-polycaprolactone copolymer as an efficient dopamine sensor platform

Amphiphilic copolymers consisting of an all conjugated polythiophene backbone and sparsely attached oligo-e-caprolactone side chains have been prepared by anodic electropolymerization of hydroxymethyl-3,4-ethylenedioxythiophene (HMeEDOT) with a thiophene-ended oligo-e-caprolactone macromonomer (Th-PCL), obtained by ring opening polymerization of e-caprolactone with thiophene methanol. The random copolymers, obtained starting from two different molar ratios of the co-monomers in the feed (HMeEDOT : Th-PCL of 80 : 20 and 60 : 40), and the homopolymer (PHMeEDOT) were synthesized by using three different working electrodes. After structural characterization by FTIR, the electrochemical, morphological and surface properties of the obtained copolymers were examined, and the results evidenced a dependence on both the working electrode and the composition in the feed. In order to evaluate the opportunities in the copolymerss further bioapplications, biodegradability, cytotoxicity and cell proliferation investigations were carried out. By combining the results of electrochemical characterization with those of biocompatibility and dopamine sensing capability tests, it was concluded that a co-monomer feed ratio of 80 : 20 could be the optimal choice for the potential use of these amphiphilic copolymers in sensing devices. All in all, this study shows the benefit of a designed “hairy-rod” conjugated polymeric architecture which, via their side chain nature (biocompatible/biodegradable, hydrophobic, oligomeric) and their grafting density, enabled the synthesis of a material for targeted application.

New mesogenic maleimide-styrene copolymers via N-oxyl mediated free radical copolymerization

New mesogenic N-substituted maleimide monomer was obtained starting 4-maleimido benzoic acid, hydroquinone and hexadecyloxy benzoic acid by successive Schotten-Bauman condensations. The copolymerization of this monomer in 1:1 ratio with styrene was performed both by stable free radical polymerization (SFRP) and conventional free radical polymerization (CFRP). High molecular weight polymeric material in high conversion and with low polydispersity was obtained under SFRP conditions. By using 1H- and 13C-NMR techniques, structural characteristics of the polymers were evidenced that could sustain the alternating character of the copolymers and the participation of the electron donor–acceptor complex in the propagation step. The copolymers formed a liquid crystal mesophase in the melt. This was ascribed to the strong tendency of the rod-like side groups on the stiff imide ring to order even in 1:1 dilute systems such as the alternating copolymers.