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Global Translational Medicine Electrical stimulation in therapy and biology

Emerging applications of ES also include soft tissue the likelihood of electrode fouling and prevents oxidative
engineering involving myogenic and chondrogenic stress, which could damage the neighboring tissues. This
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differentiation. In these cases, specific electrical parameters, is particularly essential in applications requiring prolonged
such as frequency and amplitude, are essential to obtain or regenerative uses, such as tissue engineering, where
specific results. For instance, low-frequency stimulation a constant stimulus is needed to modify cell behavior
(less than 1 kHz) promotes cartilage matrix deposition, without causing cell death.
while higher frequencies support muscle regeneration. 4 Monophasic stimulation is less safe for long-term

3.4. Optimization of ES parameters studies because it can elicit an immediate cellular reaction,
such as polarization or migration. It also exhibits high
ES is known to be sensitive to the waveform, intensity toxicity during long-term experiments. For example, high
(typically ranging from 0.1 mA to 10 mA), pulse duration currents over long periods may result in thermal effects
(ranging from 0.1 ms to 1 ms), frequency (from 1 Hz to at specific sites where current enters and exits the tissue,
1,000 Hz), and polarity of the electrical field. These potentially causing thermal damage to the cells. However,
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parameters should be manipulated to achieve the best recent advancements in electrode design have mitigated
outcome where ES can activate the intended biological some of these issues. New findings highlight that improved
response while simultaneously alleviating the negative electrode designs, such as platinum coating or conductive
impacts. For instance, studies have shown that for polymer applied to the sharpened tips of the electrodes,
skin wound recovery using surface electrodes, optimal have reduced the effects of charge deposition and improved
parameter ranges include an intensity between 1 mA and ES effectiveness. Furthermore, in the case of inductive
5 mA, a pulse duration of 100 ms to 300 ms, and a frequency or capacitive coupling, a non-invasive solution has been
between 10 Hz and 100 Hz. Such targeted configurations developed that eliminates the need to directly touch
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can enhance tissue repair and reduce inflammation while
avoiding thermal damage or oxidative stress. electrodes. These methods involve using electromagnetic
fields or capacitive plates, transmitting electric fields to
The two key parameters include waveform type cells without the risks associated with invasive electrodes,
and electrical field strength. ES encompasses various which are less effective and more dangerous. These
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techniques, including monophasic and biphasic advances also address challenges related to electrode
stimulation, used to influence cellular activity through stability and biocompatibility (Table 1).
controlled electrical currents. Biphasic stimulation, a subset
of ES, has emerged as a preferred approach in long-term 3.5. Latest developments and future directions
biomedical applications. It is characterized by alternating ES is expected to shift from conventional procedures to
polarity within each pulse, making it particularly effective complex techniques due to bioelectronics and real-time
in reducing adverse effects associated with continuous monitoring, especially from 2024. It is likely that the
stimulation. integration of intelligent systems, which will allow the
Biphasic stimulation has gained popularity, particularly stimulation parameters to be adapted based on cellular
for long-term applications, due to its ability to minimize response, will dramatically evolve ES applications. These
charge accumulation at the electrodes. Comparative systems can assess the cellular response in real time, altering
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studies indicate that biphasic stimulation typically operates parameters such as current, frequency, and waveform to
with frequencies ranging from 10 Hz to 100 Hz and pulse achieve the best therapeutic results. This approach may
durations in the range of a few microseconds to a few have the capacity to improve the accuracy and effectiveness
milliseconds per phase, while monophasic stimulation of ES therapies, particularly in regenerative medicine,
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often employs higher currents over shorter durations, where differentiation responses depend on the tissue type.
leading to increased risks of electrode fouling and tissue Another rapidly advancing area is the design of conductive
damage. These differences make biphasic stimulation scaffolds at the nanoscale. These scaffolds are engineered to
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more favorable for maintaining electrode stability and integrate with body tissues, providing mechanical support
promoting long-term cellular health. and bioelectric guidance to cells. The combination of ES

Monophasic currents may result in charge deposited with such advanced materials marks a new era in tissue
on the electrode surface and a higher likelihood of engineering, particularly in the regeneration of bones,
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electrochemical side reactions through the production cartilage, and nerve tissues.
of hazardous products such as hydrogen and oxygen. In addition, the combination of ES with additional
In contrast, biphasic waveforms are characterized by a physical cues, such as mechanical stress and light, has
reversal of polarity per pulse. This characteristic reduces provided new directions toward possible treatments.

Volume 4 Issue 3 (2025) 27 doi: 10.36922/gtm.7774