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Global Translational Medicine Electrical stimulation in therapy and biology
Figure 3. Mechanisms of action and clinical applications of electrical stimulation
ES contributed to improved tissue remodeling, repair, and and tissue remodeling. E S enhances these processes
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therapeutic outcomes. Recent studies have expanded our by modulating the interaction with adhesion molecules
understanding of these processes, integrating established and regulating the cytoskeletal rearrangements. Studies
and emerging insights into ES’s mechanism of action. involving low-amplitude direct current fields suggest that
increased receptor proteins and focal adhesion kinase
3.1. Activation of signaling pathways proteins are necessary for cell adhesion and migration into
ES activates intracellular signaling by modulating the the extracellular matrix. 4
electrical and chemical milieu of the cells. Based on The movement of cells in response to ES is referred to
the signals from applied electric fields, voltage-gated as galvanotaxis or electrotaxis. When the field strength
ion channels allow Ca² to enter the cells and initiate a is optimized, various cell types, such as keratinocytes,
+
sequence of intracellular signals. Recent research stresses fibroblasts, and even immune cells, exhibit directed
that specific ion channels, including aquaporins, mediate migration toward the cathode. These observations are
ES’s effects. For example, alternating current stimulation derived from studies using capacitive coupling systems,
increases the number of open aquaporin channels without which create homogenous electric fields. Such stimulation
altering the membrane potential, providing evidence for a promotes cell migration and increases the deposition of
selective mechanism of cell hydration and ion transport. 30 glycosaminoglycans and extracellular matrix components.
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Furthermore, ES activates the mitogen-activated These findings are clinically valuable, offering promising
protein kinase/extracellular signal-regulated kinase strategies for improving tissue repair.
and phosphatidylinositol 3 kinase/protein kinase B for
cell survival and proliferation. Studies using pulsed 3.3. Influence on growth and differentiation
electromagnetic field stimulation have shown the ES modulates stem cell behavior and fate by recreating
possibility of modulating oxidative stress by reducing physiological electrical signals. For instance, biphasic
reactive oxygen species levels and increasing antioxidant waveforms commonly used in tissue engineering of the
markers such as superoxide dismutase. This dual effect neural system enhance the differentiation of neural stem
contributes to maintaining cellular stability in physiological cells into neurons with increased neurite length and
and therapeutic states. Recent research also shows that ES branching points. Conductive scaffolds improve this impact
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plays a role in angiogenesis and inflammation by regulating by creating favorable conditions for neural regrowth.
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transcription factors such as hypoxia-inducible factor Similarly, mesenchymal stem cells undergoing pulsed ES
1-alpha and nuclear factor kappa beta. These pathways have a higher osteogenic differentiation outcome. Previous
enhance cellular metabolism and repair. Notably, the studies have shown that runt-related transcription
ability of ES to target hypoxic or damaged cells suggests factor 2 and osteopontin as essential biomarkers that are
its potential utility in treating ischemia or chronic wounds. upregulated during this process. Furthermore, culturing
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cells with biochemical signals such as sulfated hyaluronan,
3.2. Cell adhesion and migration combined with pulsed electromagnetic field stimulation,
Cell adhesion and migration are essential in various can boost bone matrix development, offering a novel
processes, such as wound healing, immune response, strategy for orthopedic medicine. 36
Volume 4 Issue 3 (2025) 26 doi: 10.36922/gtm.7774

