Conjugated Polymer-based Fibrillar Hydrogel for Tissue Engineering Applications

Abstract

Conductive polymers based hydrogel have gained immense interest due to its wide range of applications in tissue engineering and biomedical applications, including an extracellular matrix for tissue growth and regeneration, the electrode for patient monitoring and electrotherapy, and implantable bioelectronics. Owing to three-dimensional (3D) porous structure, hydrophilic characteristics, and tunable chemical and physical properties, electroconductive hydrogel mimics the extracellular matrix in tissues and is considered a good matrix for cell growth, proliferation, and migration. Proceeding towards fabrication, electroconductive hydrogels are often dealing with high cytotoxicity, low optical transparency, and high stiffness. Herein, the optically transparent films and fibrillar types of electroconductive hydrogels were prepared following the two steps, firstly, the chemical crosslinking at solid-state between the -OH of polyvinyl alcohol (PVA) and -SO3H of polystyrene sulfonate from poly (3, 4-ethylene dioxythiophene) polystyrene sulfonate (PEDOT:PSS), and secondly, the hydrogelification of the solid-state chemically crosslinked films or fibers by treating with concentrated sulfuric acid while the semi-crystalline domains of PVA due to inter-intramolecular hydrogen bonding disrupt and transform into the amorphous region. The amounts of PEDOT:PSS, thermal crosslinking duration, and hydrogelification time were fine-tunned to modulate the properties of the prepared conductive hydrogels. Physical, structural, optical, geometrical, electrochemical, mechanical, and rheological properties were investigated. We achieved comparatively higher electrical conductivity, 0.23 S/cm with a low concentration of PEDOT:PSS, 1wt% without compromising its mechanical properties. Besides, the optical transparency of fibrillar hydrogels is another crucial feature that could be advantageous to see the cells inside the scaffolds. Despite the swollen state and the presence of insulating polymers (PVA) in the network, hydrogels showed clear effective charge transportation that was confirmed by cyclic voltammetry. The volumetric capacitance, and charge carrier density were systematically investigated using electrochemical impedance spectroscopy while they showed a linear relationship with the increasing amount of PEDOT:PSS loading in the hydrogels. Moreover, cytotoxicity assay of primary cells (hippocampal neurons, and cardiomyocytes) and cell line (NIH 3T3 cells) performed in the fibrillar hydrogel showed high viability. Finally, 3D connected functional neuronal networks were successfully constructed using transparent conductive fibrillar hydrogel where substantial neurite outgrowth was observed. Thus, these results confer the feasibility of this scaffold to be used as an extracellular matrix for neuronal tissue regeneration.