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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
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