Electro-assisted printing of soft hydrogels via controlled electrochemical reactions

Hydrogels, mimicking the properties of soft tissues, are widely used in tissue engineering, drug delivery, and bioelectronics. Their tunable viscoelasticity, swelling, bioactivity, and degradation properties make them versatile materials. The integration of conductive polymers, like PEDOT, further enhances their electrical properties for bioelectronic interfaces. Current hydrogel processing methods, including polymerization initiated by light, temperature, or pH changes, along with patterning techniques like casting, direct ink writing, or lithography, often lack precise control over gelation and adhesion to other materials. Electrochemical gelation offers a promising alternative, enabling the formation of adherent hydrogels on conductive surfaces under mild conditions without chemical catalysts. Previous work demonstrated electrochemical deposition of hydrogels using electrolysis to trigger pH changes or electrodeposition of ionically crosslinked alginate. However, these methods lacked precise control over reaction kinetics due to the use of two-electrode configurations. This study introduces a three-electrode configuration with potentiostatic control, enabling precise selection and control of gelation reactions for diverse hydrogel systems.

The literature extensively covers hydrogel applications in tissue engineering, drug delivery, and bioelectronics, highlighting the need for improved control over gelation mechanisms and patterning. Previous research demonstrated the use of conductive hydrogels in controlled drug delivery, as electrode coatings, and as replacements for conductive materials in electrode arrays. While methods exist for producing hydrogels via various polymerization techniques and patterning methods, challenges remain in the integration of well-defined hydrogel systems within devices due to the need for precise control over the polymerization reactions and adhesion to other materials. Electrochemical methods offer a less explored avenue for hydrogel gelation, with previous studies focusing on electrolysis-induced pH changes to trigger gelation in chitosan and alginate. However, these approaches lack precise control over the electrochemical reactions, a limitation that this work aims to address.

This research utilizes a three-electrode setup for potentiostatic control during hydrogel formation, enabling precise control over the electrochemical reactions. The setup comprises a working electrode (WE; gold plate or ITO/PET), a counter electrode (CE; modified printing nozzle), and a pseudoreference electrode (RE; Ag/AgCl). The system is integrated with a commercial 3D printer, allowing for controlled dispensing of pre-gel solutions and patterning. Chitosan and alginate hydrogels were used as model systems. For chitosan, both precipitation (at -2V) and covalent crosslinking (at 1.8V via tetrachloroaurate generation) were explored. For alginate, ionic crosslinking was achieved via controlled water hydrolysis at various potentials (3V, 4V, 5V). A hybrid PEDOT/alginate system was also investigated, where PEDOT electropolymerization (at 1.8V) occurs concurrently with alginate gelation. Electrochemical techniques such as cyclic voltammetry (CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS) were employed for in situ characterization of the hydrogel formation and properties. The growth profiles of the hydrogels were analyzed in terms of thickness, volume, and total charge density. Finally, 2D patterning of the hydrogels was achieved by moving the printing nozzle relative to the WE during polymerization. The printed hydrogels were characterized optically to determine their dimensions. Materials used included chitosan (low and high molecular weight), sodium alginate, calcium carbonate, sodium chloride, sodium dodecyl sulfate (SDS), and 3,4-ethylenedioxythiophene (EDOT).

The three-electrode potentiostatic setup enabled precise control over hydrogel formation. Different gelation mechanisms were achieved for chitosan (precipitation and covalent crosslinking) and alginate (ionic crosslinking). The growth rate of the hydrogels was found to be dependent on the applied potential and the molecular weight of the polymer. Higher potentials generally led to faster growth, but growth plateaued beyond a certain thickness due to mass transport limitations. The relationship between the total charge supplied and hydrogel thickness was quantified for both chitosan and alginate. The hybrid PEDOT/alginate system demonstrated successful simultaneous polymerization of PEDOT and gelation of alginate, resulting in a conductive hydrogel. Electrochemical impedance spectroscopy revealed differences in the electrical properties of the different hydrogel types, with the PEDOT/alginate hybrid exhibiting significantly lower resistance and higher capacitance. The 3D printing setup enabled the creation of various 2D patterns of the hydrogels on gold and flexible ITO substrates, demonstrating the versatility of the method. Good adhesion of the PEDOT/alginate hydrogel to the flexible ITO substrate was confirmed even under bending.

This study demonstrates a significant advancement in hydrogel fabrication and patterning, offering precise control over gelation mechanisms not achievable with previous methods. The potentiostatic control using a three-electrode system is key to selecting and controlling specific electrochemical reactions, resulting in hydrogels with defined properties. The ability to create hybrid conductive hydrogels opens up new possibilities for bioelectronic applications. The compatibility with flexible substrates and demonstrated 2D patterning significantly improves the integration potential for various devices. The findings address the limitations of existing hydrogel processing methods by offering a precise, controllable, and versatile approach.

This work introduces a novel electro-assisted printing method for creating patterned hydrogels with precise control over gelation. The three-electrode setup enables selection and control of different gelation mechanisms (ionic, covalent, and hybrid) and allows for the creation of conductive hydrogels. The integration with a commercial 3D printer facilitates 2D patterning on various substrates, including flexible electronics. This method represents a significant advancement in hydrogel processing with potential applications in bioelectronics and other fields. Future research could focus on exploring a wider range of hydrogel materials, optimizing printing parameters for complex 3D structures, and investigating the long-term stability and biocompatibility of the printed hydrogels in biological environments.

The current study focuses on 2D patterning. Extending the method to 3D printing requires further optimization of printing parameters and may necessitate modifications to the printing setup. The long-term stability and biocompatibility of the printed hydrogels in physiological environments need to be further investigated. While the study demonstrates good adhesion to the substrates used, further investigation into adhesion on other materials is necessary. The current study investigates a limited range of hydrogel materials and only a few specific applications.