Electroactive Oligoaniline-Containing Self-Assembled Monolayers for Tissue Engineering Applications

Abstract

A novel electroactive silsesquioxane precursor, N-(4-aminophenyl)-N'-(4'-(3-triethoxysilyl-propyl-ureido) phenyl-1,4-quinonenediimine) (ATQD), was successfully synthesized from the emeraldine form of amino-capped aniline trimers via a one-step coupling reaction and subsequent purification by column chromatography. The physicochemical properties of ATQD were characterized using mass spectrometry as well as by nuclear magnetic resonance and UV-vis spectroscopy. Analysis by cyclic voltammetry confirmed that the intrinsic electroactivity of ATQD was maintained upon protonic acid doping, exhibiting two distinct reversible oxidative states, similar to polyaniline. The aromatic amine terminals of self-assembled monolayers (SAMs) of ATQD on glass substrates were covalently modified with an adhesive oligopeptide, cyclic Arg-Gly-Asp (RGD) (ATQD-RGD). The mean height of the monolayer coating on the surfaces was approximately 3 nm, as measured by atomic force microscopy. The biocompatibility of the novel electroactive substrates was evaluated using PC12 pheochromocytoma cells, an established cell line of neural origin. The bioactive, derivatized electroactive scaffold material, ATQD-RGD, supported PC12 cell adhesion and proliferation, similar to control tissue-culture-treated polystyrene surfaces. Importantly, electroactive surfaces stimulated spontaneous neuritogenesis in PC12 cells, in the absence of neurotrophic growth factors, such as nerve growth factor (NGF). As expected, NGF significantly enhanced neurite extension on both control and electroactive surfaces. Taken together, our results suggest that the newly electroactive SAMs grafted with bioactive peptides, such as RGD, could be promising biomaterials for tissue engineering.

Preparation and Characterization of Biodegradable and Electroactive Polymer Blend Materials Based on mPEG/Tetraaniline and PLLA

“…Guo et al [12] synthesized the biodegradable multi-armed branched poly(L-lactides) bearing aniline trimer segments and the polymer showed good solubility and redox properties. Wei et al [13] demonstrated that an electroactive silsequioxane precursor containing aniline trimer covalently modified by using an oligopeptide could be a promising biomaterial for tissue engineering. In our previous work, electroactive polymers with good electroactivity and biodegradability such as multi-block copolymer PLAAP of polylactide (PLA), aniline pentamer (AP), and water-soluble polymer AP cross-linking chitosan (CS) were synthesized.…”

Enhanced Cardiac Differentiation of Mouse Embryonic Stem Cells by Electrical Stimulation

“…More recently Rangappa et al [76] reported that human mesenchymal stem cells, when juxtaposed and in direct (electrical) contact with human cardiac myocytes, can be reprogrammed into the cardiomyogenic lineage. Similarly, prior studies have suggested that specific differentiative cues could be tailored into artificial scaffolds to help efficiently direct stem cell fate decisions [77,78,59,7,6,79].…”

“…Subsequently a few groups, including us, have started to reduce into practice the idea of modulating the differentiation of stem and progenitor cells using electrical currents and, hence, generating more efficiently "better" tissue-engineered constructs [59,60,6]. Given the importance of stem cells as general cell sources for tissue engineering and regenerative medicine, and specifically of electrical currents and stimulation for neural, cardiac, and musculoskeletal tissue engineering, it is astonishing that only very few groups have thus far published on optimizing stem cell differentiation by using electrical stimulation.…”

“…Three-dimensional scaffolds comprised of nanofibers, and incorporating specific biological components, including electrical signaling, will be uniquely suited to mimic some of the matrix-resident cues, which fine-tune cellular differentiation and function in vivo. Of late, porous and fibrous scaffolds or 2D substrates containing electrically conductive and electroactive polymers, such as polypyrrole or polyaniline, were shown to enhance neuronal and cardiac differentiation [5][6][7]. For example, polyaniline, after initial passivation treatment, supports cell growth and proliferation while remaining conductive for at least 100 h [7] while polyaniline films induced neuronal differentiation of PC12 cells in the absence of electrical stimulation [8].…”

Nanomembranes and Nanofibers from Biodegradable Conducting Polymers

“…Wei et al [41] demonstrated that an electroactive silsequioxane precursor containing an aniline trimer [i.e., N-(4-aminophenyl)-N′-(4′- (3-triethoxysilyl-propyl-ureido) phenyl-1,4-quinonenediimine) (ATQD)] could be a promising biomaterial for tissue engineering. To this end, self-assembled monolayers of ATQD on glass substrates were covalently modified with an adhesive oligopeptide, cyclic Arg-Gly-Asp (RGD) (Figure 6).…”