Beatrice Lang
Electrical stimulation of cells is a process that applies an electric current to cells to change their function or behaviour. This technique has been used in various applications, including regenerative medicine, tissue engineering, and disease treatment. Electrical stimulation can be delivered through direct coupling, capacitive coupling, or using an electromagnetic field. The effects of electrical stimulation vary depending on the type of cell and the stimulation parameters, such as frequency, electrical strength, and duration. In most cases, electrical stimulation facilitates cell proliferation, differentiation, and migration. For example, electrical stimulation has been shown to enhance nerve function recovery and improve motor function after a stroke.
| Characteristics | Values |
|---|---|
| Purpose | Tissue engineering, regenerative medicine, disease treatment, wound healing, mechanism study |
| Types of electrical stimulation | Direct coupling, capacitive coupling, inductive coupling, electromagnetic field stimulation (EMF) |
| Types of current | Direct current (DC), alternative current (AC), monophasic pulsed current, biphasic pulsed current |
| Effects | Cell proliferation, differentiation, migration, gene expression, cell behaviour, cell activation, cell adhesion, cell survival, apoptosis, protein transduction, collagen deposition, angiogenesis, blood flow, metabolism, tissue shape and size |
| Equipment | Electrodes, coils, cell culture plates, conductive materials, conductive substrate, tissue scaffolds, conductive coils |
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What You'll Learn
Using electrodes
Electrodes are the most popular tools for applying electrical stimulation to cells or tissues, likely due to their simplicity. However, people use electrodes in different ways, and the data are hardly comparable.
One common method is to place two electrodes at opposite ends to provide a uniform electric field to the cells seeded on a scaffold that is placed between the electrodes. This system is non-invasive and does not require a conductive scaffold to provide uniform electrical stimulation.
Another method is to use a commercially-available stimulation electrode board, such as the C-Dish™ from IonOptix, in combination with other discrete electrical equipment. The C-Dish™ stimulation board is designed to be used with the C-Pace EP Cell Stimulator (IonOptix, USA), with pulsed waveforms ranging from 1–100 Hz. However, it is limited to DC and pulsed voltages (monophasic and biphasic) and does not have kHz frequency outputs.
When using electrodes for electrical stimulation, it is important to consider the size and pitch of the electrodes, as this can impact the resolution and targeting of the stimulation. Traditional microelectrode arrays have larger electrode sizes, which may not allow for stimulation at the subcellular level or reliable single-neuron targeting. High-density microelectrode arrays, on the other hand, offer higher spatial resolution and a larger overall sensing area, making them more suitable for single-cell electrical stimulation.
To confirm that the desired cells are effectively stimulated, techniques such as superimposing the "electrical footprints" of spontaneous activity with the spatial distribution of stimulation-evoked EAPs can be employed. This allows for the identification of the stimulated neuron through its unique electrical "footprint" and the spatial distribution of extracellular APs.
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Direct coupling
Direct coupled electrical stimulation has been shown to promote multiple cellular processes, including cell migration, proliferation, and osteogenic differentiation. It is particularly useful for bone tissue engineering, promoting vital cellular processes and enhancing cell proliferation, migration, and differentiation.
To perform direct coupled electrical stimulation, a constant direct coupled (DCoupled) current stimulation protocol is applied. This can be done through the use of different setups, electrode or substrate materials, and a variety of waveforms. Electrodes are the most popular tools for applying electrical stimulation to cells or tissues due to their simplicity.
For example, in one study, a silver electrode and a platinum electrode were inserted into the opposite ends of a nanofibre scaffold placed in the medium and connected to constant unipolar trapezoidal pulses. This resulted in a nearly 100% higher average length of neurites extended from NSCs with stimulation compared to those without.
Another example is the use of piezoelectric biomaterials, which can generate piezoelectrical charges in response to mechanical activation. These charges can directly stimulate bone regeneration by triggering signalling pathways that regulate osteogenesis of cells seeded on the materials.
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Capacitive coupling
The geometry of the experimental setup for capacitively-coupled electrical stimulation of cells is often modelled as a cylindrical layered geometry. Two circular metallic plates are separated from the culture medium by electrically insulating layers, typically plastic, glass, or air. In this setup, the culture plate is sandwiched between two parallel plates, with the distance between the plates and the culture minimised to reduce resistance.
In capacitive coupling, two typically parallel flat metal electrodes are separated from the culture medium by an insulating layer. No electron transfer reactions occur at the insulator-electrolyte interface. One drawback of capacitively-coupled systems is that the voltage drop across the culture medium is only a fraction of the applied voltage.
Numerical simulations, such as the Finite Element Method (FEM), can be used to estimate the transmembrane potential (TMP). This method can be used to avoid a full discretization of the cell membrane, which would lead to prohibitively expensive models.
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Inductive coupling
The use of inductive coupling in electrical stimulation of cells offers several advantages. Firstly, it bypasses issues associated with electrodes, such as cytotoxicity, tissue compatibility, charge transfer, electrode surface modification, and corrosion. Secondly, it allows for the generation of uniform electric fields without the need for a conductive scaffold. Finally, inductive coupling can be used to generate controllable electromagnetic fields, providing flexibility in the delivery of electrical stimulation.
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Tissue engineering
Electrical stimulation (ES) is a rapidly evolving field that has gained attention as a novel tool for regulating cell behaviour in tissue engineering. It has shown great potential in disease treatment, wound healing, and mechanism study. In tissue engineering, ES is used to influence cellular behaviour for regenerative medicine applications. The three key factors of regenerative medicine and tissue engineering are seed cell, scaffold, and stimulating factor.
The seed cell is the specific cell type that is delivered to the damaged site through the scaffold. The scaffold acts as a medium to provide stimuli and support for the cells, mimicking the natural tissue's mechanical and biological properties. It ensures in vivo support, optimum diffusion of nutrients, and encourages cellular communication. To deliver ES, scaffolds must have excellent biocompatibility, prominent electrochemical performance, and no byproduct generation.
Scaffolds can be made of metallic biomaterials, conducting polymers, or carbon materials. Platinum and gold are commonly used due to their high mechanical strength, long-term stability, good conductivity, and biocompatibility. However, other metallic materials may be easily oxidized and have weak corrosion resistance. Conductive biomaterials, such as poly(lactic‐co‐glyological acid) (PLGA) and poly(l‐lactide)‐aniline pentamer triblock copolymer (PAP), can enhance the conduction of electrical signals between cells, further improving the effectiveness of ES.
There are three main methods to deliver ES: direct coupling, capacitive coupling, and using an electromagnetic field. By combining specific materials and structures with ES, it is possible to achieve precise cellular regulation and influence cell proliferation, differentiation, migration, and alignment. However, challenges remain in developing safe and effective partition-type scaffolds that can distinguish different areas for performing different stimulations.
Overall, ES is a promising tool for tissue engineering, offering potential advantages over other types of stimulations and contributing to advancements in regenerative medicine and disease treatment.
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Frequently asked questions
Electrical stimulation (ES) is a process by which an electrical current is applied to cells to change their function or behavior.
There are three main methods of delivering electrical stimulation: direct coupling, capacitive coupling, and using an electromagnetic field.
Electrodes are the most popular tools used to apply electrical stimulation to cells or tissues. Other equipment may include coils, plates, and scaffolds, depending on the method of stimulation.
Electrical stimulation can cause cells to become more active, increase their metabolism, and change their gene expression. It can also promote cell migration, proliferation, and differentiation, and has been shown to be effective in treating various medical conditions.
