Synthesis, copolymerization and peptide-modification of carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) for neural electrode interfaces.

BACKGROUND: Conjugated polymers have been developed as effective materials for interfacing prosthetic device electrodes with neural tissue. Recent focus has been on the development of conjugated polymers that contain biological components in order to improve the tissue response upon implantation of these electrodes. METHODS: Carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) monomer was synthesized in order to covalently bind peptides to the surface of conjugated polymer films. EDOTacid was copolymerized with EDOT monomer to form stable, electrically conductive copolymer films referred to as PEDOT-PEDOTacid. The peptide GGGGRGDS was bound to PEDOT-PEDOTacid to create peptide functionalized PEDOT films. RESULTS: The PEDOT-PEDOTacid-peptide films increased the adhesion of primary rat motor neurons between 3 and 9 times higher than controls, thus demonstrating that the peptide maintained its biological activity. CONCLUSIONS: The EDOT-acid monomer can be used to create functionalized PEDOT-PEDOTacid copolymer films that can have controlled bioactivity. GENERAL SIGNIFICANCE: PEDOT-PEDOTacid-peptide films have the potential to control the behavior of neurons and vastly improve the performance of implanted electrodes. This article is part of a Special Issue entitled Organic Bioelectronics-Novel Applications in Biomedicine.

Recent advances in fluorescent and colorimetric conjugated polymer-based biosensors.

Conjugated polymers recently have drawn much attention as an emerging sensory material due to their meritorious signal amplification, convenient optical detection, readily tunable properties, and easy fabrication. We review the molecular design principles of sensory conjugated polymer recognition events, which can trigger conformational change of the conjugated polymer, induce intermolecular aggregation, or change the distance between the conjugated polymer as an energy donor and the reporter dye molecule as an energy acceptor. These recognition/detection mechanisms result in mainly three types of measurable signal generation: turn on or turn off fluorescence, or change in either visible color or fluorescence emission color of the conjugated polymer. In this article, we highlight recent advances in fluorescent and colorimetric conjugated polymer-based biosensors.

In situ polymerization of a conductive polymer in acellular muscle tissue constructs.

We present a method to chemically deposit a conductive polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), on acellularized muscle tissue constructs. Morphology and structure of the deposition was characterized using optical and scanning electron microscopies (SEM). The micrographs showed elongated, smooth, tubular PEDOT structures completely penetrating and surrounding the tissue fibers. The chemical polymerization was performed using iron chloride, a mild oxidizer. Remaining iron and chlorine in the tissue constructs were reduced to acceptable metabolic levels, while preserving the structural integrity of the tissue. We expect that these acellular, polymerized tissue implants will remain essentially unmodified in cellular environments in vitro and in vivo because of the chemical and thermal stability of the PEDOT polymer depositions. Our results indicate that in situ polymerization occurs throughout the tissue, converting it into an extensive acellular, non-antigenic substrate of interest for in vivo experiments related to nerve repair and bioartificial prosthesis. We expect these conducting polymer scaffolds to be useful for direct integration with electronically and ionically active tissues.

Polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) around living neural cells.

In this paper, we describe interactions between neural cells and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) toward development of electrically conductive biomaterials intended for direct, functional contact with electrically active tissues such as the nervous system, heart, and skeletal muscle. We introduce a process for polymerizing PEDOT around living cells and describe a neural cell-templated conducting polymer coating for microelectrodes and a hybrid conducting polymer-live neural cell electrode. We found that neural cells could be exposed to working concentrations (0.01 m) of the EDOT monomer for as long as 72 h while maintaining 80% cell viability. PEDOT could be electrochemically deposited around neurons cultured on electrodes using 0.5-1 microA/mm(2) galvanostatic current. PEDOT polymerized on the electrode and surrounded the cells, covering cell processes. The polymerization was impeded in regions where cells were well adhered to the substrate. The cells could be removed from the PEDOT matrix to generate a neural cell-templated biomimetic conductive substrate with cell-shaped features that were cell attracting. Live cells embedded within the conductive polymer matrix remained viable for at least 120 h following polymerization. Dying cells primarily underwent apoptotic cell death. PEDOT, PEDOT+live neurons, and neuron-templated PEDOT coatings on electrodes significantly enhanced the electrical properties as compared to the bare electrode as indicated by decreased electrical impedance of 1-1.5 orders of magnitude at 0.01-1 kHz and significantly increased charge transfer capacity. PEDOT coatings showed a decrease of the phase angle of the impedance from roughly 80 degrees for the bare electrode to 5-35 degrees at frequencies >0.1 kHz. Equivalent circuit modeling indicated that PEDOT-coated electrodes were best described by R(C(RT)) circuit. We found that an RC parallel circuit must be added to the model for PEDOT+live neuron and neuron-templated PEDOT coatings.