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International Journal of Bioprinting 3D printable conductive composite inks for biocompatible electrodes
suggested that recapitulating the physical and chemical types of composite inks, conductive ink fabricated by blending
microenvironment of the tissue enhances the performance conductive fillers into biocompatible polymers has been
of the engineered tissues . The Electrophysiology of tissue proposed as a novel material for biocompatible electrodes.
[1]
has caught attention as an important property, [2,3] because The high capacitance and elasticity potentiate the conductive
the tissue functions are regulated by their own or innervated ink as a safe electrode material with a low risk of damage to the
nerve’s electrical activities. External electrical stimulation electrode and tissue [20-22] . The conductive fillers not only affect
induces the depolarization of the cell membrane, and the conductivity of the polymers but also their rheological
the modification of the intracellular dynamics and ion properties and printability. In general, a high concentration of
concentration. Intracellular activities contribute to changes fillers results in high conductivity, instead of low printability
in the morphology of cells and the secretion of proteins or due to high viscosity and clogging of the nozzle. As high
hormones, which affect cell behaviors, such as migration , conductivity is preferable to reduce the effect of leakage
[4]
[8]
proliferation [5-7] , differentiation , and maturation [9-11] . current, determining an appropriate concentration of fillers
The in vitro cell culture platform integrated with is essential to achieve the best conductivity and printability.
electrodes has emerged as a promising approach to exert However, the nonlinear characteristic of conductivity and
electrical stimulation and has been shown to demonstrate their relationship with the filler morphology makes predicting
meaningful results; however, the exact mechanisms of the optimum concentration of fillers difficult.
each cell function modulation have yet to be delineated. Increasingly, many studies on 3D volumetric tissue
In addition, the electrical stimulation properties used in structures have been published, and 3D volumetric
in vitro culture platform should be optimized. Direct structures are known to be able to better replicate the
current and alternating current influence cells with tissue microenvironment compared to 2D structures [23,24] .
different mechanisms, and the voltage, current, frequency, Commonly used platforms could not exert even electrical
pulse width, and duration affect the viability and behaviors stimulation to 3D structures, thus lowering the reproducibility
of the cell . Therefore, controlled microenvironment and and consistency of the results. 3D printing with conductive
[12]
optimized electrical stimulation properties have always ink facilitates the adjustment of printed features with electrode
been an essential goal for the optimization of stimuli and size, shape, number, and chamber size and shape. The assembly
precise analysis. of bioink and conductive ink is assisted by multi-material
In general, in vitro cell culture platforms for electrical 3D printing, which can simultaneously construct intricate
[25]
stimulation comprise two electrodes, which are placed structures with multiple nozzles and inks . Therefore, ink
into the aqueous media, as shown in Figure 1A. The with conductive fillers play a critical role in 3D printing due
to its high conductivity, printability, and biocompatibility with
external stimulator applies a constant voltage or current variable rheological properties.
to the electrodes, while the tissue is cultured between
the electrodes, where the electrical field is exerted. The First, this review discusses the mechanism of the
electrodes are frequently composed of biocompatible rheology and conductivity change with the introduction
metals (e.g., platinum [11,13,14] or titanium ) or carbon of the filler. Next, we summarize some applications of
[15]
rods . However, metal electrodes have a risk of irreversible conductive ink with different fillers, such as metals, carbon-
[12]
faradaic reactions due to their low charge injection based materials, and MXene. Lastly, this review examines
capacity [16,17] , while carbon rods might rupture, generating the current state and proposes future directions on
harmful carbon particles due to their brittleness. In electrode integrated tissue culturing platforms fabricated
addition, the high mechanical properties and brittleness of ion using conductive ink for electrical stimulation or
the metal and carbon electrodes have been vital drawbacks sensing of engineered tissue.
for various applications with different sizes and designs. 2. Basic properties of ink with fillers for the
To address the current challenges in developing advanced
electrical stimulation systems with high versatility, three- extrusion-based printing process
dimensional (3D) printing technology is exploited as the 2.1. Understanding rheological properties as criteria
standard fabrication method with high spatial resolution of the extrusion process
that can apply various inks .
[18]
The extrusion-based printing process requires precise
Composite ink provides high flexibility in achieving various manipulation of printing parameters (e.g., nozzle
needs as ink for extrusion-based printing. The incorporation size, pressure, and feed rate) for high accuracy and
of insoluble fillers (e.g., nanoparticles, nanotubes, and fibers) reproducibility . The decision of parameters largely
[26]
into the composite ink affects the printability, mechanical and depends on the rheological property of the ink.
structural properties, and conductivity . Among various Furthermore, the rheological property of the ink
[19]
Volume 9 Issue 1 (2023) 288 https://doi.org/10.18063/ijb.v9i1.643

