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.

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.

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Graft copolymers formed by anchoring poly(ethylene glycol) (PEG) chains to conjugated polythiophene have been prepared by copolymerizing two compounds: . The electroactivity and electrochemical stability of PTh 3 * -g-PEG is not only higher than that of PTh 5 -g-PEG but also higher than that of PTh 3 , the latter presenting a very compact structure that makes difficult the access and escape of dopant ions into the polymeric matrix during the redox processes. Furthermore, the optical - * lowest transition energy of PTh 3 * -g-PEG is lower than that of both PTh 5 -g-PEG andPTh 3 . These properties, combined with suitable wettability and roughness, result in an excellent behavior as bioactive platform of PTh 3 * -g-PEG copolymers, which are more biocompatible, in terms of cellular adhesion and proliferation, and electro-compatible than PTh 5 -g-PEG.

New amphiphilic poly(ethylene glycol) (PEG)-grafted random intrinsically conducting copolymers which combine three different functionalities have been engineered, prepared and characterized. Specifically, these "rod-coil" type copolymers bear conducting polypyrrole (PPy) and poly(Schiff base) (PSB) sequences randomly distributed in their backbones; hydrophilic grafted side chains consisting of well-defined PEG chains are attached to the PSB units. Basically, the synthesis of the copolymers is conducted sequentially by employing the "macromonomer" technique via electrochemical co-polymerization of a bis ( pyrrole) benzoic Schiff base-containing PEG macromonomer with pyrrole monomers. After investigation of the chemical and electrochemical properties of the synthesized copolymers, their advantages of multi-functionality in terms of biomedical applications have been demonstrated. More specifically, the conjugated PPy and PSB sequences enabled the grafted copolymers to exhibit great ability to catalyse the oxidation of serotonin, an important neurotransmitter found in blood platelets and in the central nervous systems of animals and humans. On the other hand, the enhanced biocompatibility in comparison with bare PPy is due to the presence of PEG side chains, while bacteriostatic activity against both Gram-negative and Gram-positive bacteria is imparted by the synergistic combination of the polycationic character of the PPy main chain with the benzoic Schiff base functional groups and with the bent-shaped architecture of the facially amphiphilic PSB sequences, respectively. Accordingly, these grafted copolymers are promising materials for developing implantable electrodes for serotonin detection which present the abovementioned characteristics. c "Petru

Design of an amphiphilic heterografted block copolymer composed of a hydrophobic core backbone and both hydrophilic side chains, able to detect the redox reaction of NADH.

End-group functionalization of homopolymers is a valuable way to produce high-fidelity nanostructured and functional soft materials when the structures obtained have the capacity for self-assembly (SA) encoded in their structural details. Herein, an end-functionalized PCL with a π-conjugated EDOT moiety, (EDOT-PCL), designed exclusively from hydrophobic domains, as a functional “hydrophobic amphiphile”, was synthesized in the bulk ROP of ε-caprolactone. The experimental results obtained by spectroscopic methods, including NMR, UV-vis, and fluorescence, using DLS and by AFM, confirm that in solvents with extremely different polarities (chloroform and acetonitrile), EDOT-PCL presents an interaction- and structure-based bias, which is strong and selective enough to exert control over supramolecular packing, both in dispersions and in the film state. This leads to the diversity of SA structures, including spheroidal, straight, and helical rods, as well as orthorhombic single crystals, with solvent-dependent shapes and sizes, confirming that EDOT-PCL behaves as a “block-molecule”. According to the results from AFM imaging, an unexpected transformation of micelle-type nanostructures into single 2D lamellar crystals, through breakout crystallization, took place by simple acetonitrile evaporation during the formation of the film on the mica support at room temperature. Moreover, EDOT-PCL’s propensity for spontaneous oxidant-free oligomerization in acidic media was proposed as a presumptive answer for the unexpected appearance of blue color during its dissolution in CDCl3 at a high concentration. FT-IR, UV-vis, and fluorescence techniques were used to support this claim. Besides being intriguing and unforeseen, the experimental findings concerning EDOT-PCL have raised new and interesting questions that deserve to be addressed in future research.