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Bioengineering
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Electromagnetic Regenerative Bioengineering: Updates and Future Directions
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Electromagnetic Regenerative Bioengineering: Updates and Future Directions

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 18330

Special Issue Editor

Prof. Alfredo Franco-Obregón

E-Mail Website
Guest Editor
Department of Surgery, iHealthTech, National University Singapore, Singapore
Interests: Mechanobiology; Electromagnetics; Electrophysiology; Flow Cytometry; Genetic and Regenerative Engineering Electromagnetics; Genetic and Regenerative Engineering

Special Issue Information

Dear Colleagues,

Life on Earth evolved in an electromagnetic realm. Accordingly, a growing body of data is now providing clear proof that electromagnetism is an authentic developmental force. Paradoxically, the shear diversity of magnetic field paradigms being explored in scientific studies in combination with the disparate manner in which a given magnetic paradigm can influence tissue development, depending on the duration and intensity of exposure, has inadvertently created a sense of discordance for the field. This is an unfortunate situation that can be partially remedied with the existence of accurate information. Magnetic fields represent a form of adaptive stress impinging on mitochondrial function that may either promote or undermine cell survival depending on exposure parameters and therefore, if carefully designed, can be exploited for either the targeted strengthening (for health) or demise (disease control) of cells while precisely tuning the exposure. In this Issue of Bioengineering, we aim to bring resolution to the field of electromagnetics by discussing the following: (1) the most common types of electromagnetic field paradigms employed in scientific studies; (2) the molecular moieties and cellular pathways that are most commonly targeted by electromagnetic paradigms; (3) the developmental programs most commonly cited to be modulated by said electromagnetic paradigms; and (4) potential synergisms of magnetic fields with other biophysical stimuli of developmental consequence, such as light and mechanical forces, or with biomaterials that may help focus magnetic field exposure for improved developmental outcomes.

Prof. Alfredo Franco-Obregón

Guest Editor

Manuscript Submission Information

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Keywords

  • mitochondria

  • oxidative stress
  • electromagnetism
  • ROS (reactive oxygen species)
  • photons
  • calcium channels
  • cancer
  • regenerative medicine

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Published Papers (5 papers)

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Research

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15 pages, 3809 KiB  
Article
The Effect of Static Magnetic Fields of Different Strengths and Polarities on Cytokine Production by Human Lymphocytes In Vitro
by Vladimir Turuntaš, Silvio de Luka, Jasna L. Ristić-Djurovic, Saša Ćirković, Drago Djordjevich, Siniša Ristić, Nenad Lalović, Veljko Marić, Bratislav Lazić, Bojan Joksimović, Ivan Stanojevic, Saša Vasilijić and Alexander M. Trbovich
Bioengineering 2024, 11(8), 749; https://doi.org/10.3390/bioengineering11080749 - 24 Jul 2024
Cited by 1 | Viewed by 1982
Abstract
In contrast to electromagnetic fields, static magnetic fields (SMFs) have not been extensively studied in terms of their potential health consequences. Although upward- and downward-oriented magnetic poles may cause various biological effects, only the pole with the upward orientation has been mainly investigated. [...] Read more.
In contrast to electromagnetic fields, static magnetic fields (SMFs) have not been extensively studied in terms of their potential health consequences. Although upward- and downward-oriented magnetic poles may cause various biological effects, only the pole with the upward orientation has been mainly investigated. Considering that the interaction of antigen-presenting cells (APCs) and T lymphocytes is crucial to trigger an immune response, we assessed the effect of long-term exposure of human T lymphocytes and dendritic cells (DCs) to moderate strength SMFs of different orientations focusing on the cytokine profile of activated T cells. Cultures of allogenic T lymphocytes and DCs (immature and matured by TLR3 and TLR7 agonists) were continuously exposed to four SMFs. The intensity of the applied field was 1 militesla (mT) or 56 mT of the upward- and downward-oriented pole of the SMF. Cell culture supernatants were assayed for IFN-γ, IL-4, IL-17, TNF-α, TNF-β, IL-1 β, IL-6, IL-8, and IL-10 by ELISA or flow cytometry. The upward-oriented 56 mT SMF significantly increased the release of IFN-γ and TNF-β (both p < 0.05) in the cell culture supernatants of T cells and immature DCs. In contrast, the same cultures exposed to the upward-oriented 1 mT SMF showed significantly elevated levels of IL-17 (p < 0.05). The levels of IL-4, TNF-α, IL-1 β, IL-6, IL-8, and IL-10 were not affected by the upward-oriented SMF. The downward-oriented 56 mT SMF increased TNF-α release when T cells were stimulated with mature DCs. The production of other cytokines was unchanged by the downward-oriented SMF. These findings demonstrate for the first time different in vitro biological effects of upward- and downward-oriented static magnetic fields on the cytokine production of T cells activated by DCs, helping to better understand SMF effects on the immune system and suggesting that the selective SMF effect on the immune response could have potential therapeutic effects in different immune-mediated disorders. Full article
(This article belongs to the Special Issue Electromagnetic Regenerative Bioengineering: Updates and Future Directions)
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13 pages, 3201 KiB  
Article
Synergistic Cellular Responses Conferred by Concurrent Optical and Magnetic Stimulation Are Attenuated by Simultaneous Exposure to Streptomycin: An Antibiotic Dilemma
by Jan Nikolas Iversen, Jürg Fröhlich, Yee Kit Tai and Alfredo Franco-Obregón
Bioengineering 2024, 11(7), 637; https://doi.org/10.3390/bioengineering11070637 - 21 Jun 2024
Cited by 3 | Viewed by 2264
Abstract
Concurrent optical and magnetic stimulation (COMS) combines extremely low-frequency electromagnetic and light exposure for enhanced wound healing. We investigated the potential mechanistic synergism between the magnetic and light components of COMS by comparing their individual and combined cellular responses. Lone magnetic field exposure [...] Read more.
Concurrent optical and magnetic stimulation (COMS) combines extremely low-frequency electromagnetic and light exposure for enhanced wound healing. We investigated the potential mechanistic synergism between the magnetic and light components of COMS by comparing their individual and combined cellular responses. Lone magnetic field exposure produced greater enhancements in cell proliferation than light alone, yet the combined effects of magnetic fields and light were supra-additive of the individual responses. Reactive oxygen species were incrementally reduced by exposure to light, magnetics fields, and their combination, wherein statistical significance was only achieved by the combined COMS modality. By contrast, ATP production was most greatly enhanced by magnetic exposure in combination with light, indicating that mitochondrial respiratory efficiency was improved by the combination of magnetic fields plus light. Protein expression pertaining to cell proliferation was preferentially enhanced by the COMS modality, as were the protein levels of the TRPC1 cation channel that had been previously implicated as part of a calcium–mitochondrial signaling axis invoked by electromagnetic exposure and necessary for proliferation. These results indicate that light facilitates functional synergism with magnetic fields that ultimately impinge on mitochondria-dependent developmental responses. Aminoglycoside antibiotics (AGAs) have been previously shown to inhibit TRPC1-mediated magnetotransduction, whereas their influence over photomodulation has not been explored. Streptomycin applied during exposure to light, magnetic fields, or COMS reduced their respective proliferation enhancements, whereas streptomycin added after the exposure did not. Magnetic field exposure and the COMS modality were capable of partially overcoming the antagonism of proliferation produced by streptomycin treatment, whereas light alone was not. The antagonism of photon-electromagnetic effects by streptomycin implicates TRPC1-mediated calcium entry in both magnetotransduction and photomodulation. Avoiding the prophylactic use of AGAs during COMS therapy will be crucial for maintaining clinical efficacy and is a common concern in most other electromagnetic regenerative paradigms. Full article
(This article belongs to the Special Issue Electromagnetic Regenerative Bioengineering: Updates and Future Directions)
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12 pages, 2187 KiB  
Communication
Magnetic Field Intervention Enhances Cellular Migration Rates in Biological Scaffolds
by Amy M. Vecheck, Cameron M. McNamee, Renee Reijo Pera and Robert J. Usselman
Bioengineering 2024, 11(1), 9; https://doi.org/10.3390/bioengineering11010009 - 22 Dec 2023
Cited by 1 | Viewed by 2675
Abstract
The impact of magnetic fields on cellular function is diverse but can be described at least in part by the radical pair mechanism (RPM), where magnetic field intervention alters reactive oxygen species (ROS) populations and downstream cellular signaling. Here, cellular migration within three-dimensional [...] Read more.
The impact of magnetic fields on cellular function is diverse but can be described at least in part by the radical pair mechanism (RPM), where magnetic field intervention alters reactive oxygen species (ROS) populations and downstream cellular signaling. Here, cellular migration within three-dimensional scaffolds was monitored in an applied oscillating 1.4 MHz radiofrequency (RF) magnetic field with an amplitude of 10 µT and a static 50 µT magnetic field. Given that cellular bioenergetics can be altered based on applied RF magnetic fields, this study focused on a magnetic field configuration that increased cellular respiration. Results suggest that RF accelerated cell clustering and elongation after 1 day, with increased levels of clustering and cellular linkage after 7 days. Cell distribution analysis within the scaffolds revealed that the clustering rate during the first day was increased nearly five times in the RF environment. Electron microscopy provided additional topological information and verified the development of fibrous networks, with a cell-derived matrix (CDM) visualized after 7 days in samples maintained in RF. This work demonstrates time-dependent cellular migration that may be influenced by quantum biology (QB) processes and downstream oxidative signaling, enhancing cellular migration behavior. Full article
(This article belongs to the Special Issue Electromagnetic Regenerative Bioengineering: Updates and Future Directions)
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15 pages, 3553 KiB  
Article
Concurrent Optical- and Magnetic-Stimulation-Induced Changes on Wound Healing Parameters, Analyzed by Hyperspectral Imaging: An Exploratory Case Series
by Jürg Traber, Thomas Wild, Jörg Marotz, Martin C. Berli and Alfredo Franco-Obregón
Bioengineering 2023, 10(7), 750; https://doi.org/10.3390/bioengineering10070750 - 23 Jun 2023
Cited by 6 | Viewed by 2385
Abstract
The effects of concurrent optical and magnetic stimulation (COMS) therapy on wound-healing-related parameters, such as tissue oxygenation and water index, were analyzed by hyperspectral imaging: an exploratory case series. Background: Oedema and inadequate perfusion have been identified as key factors in delayed [...] Read more.
The effects of concurrent optical and magnetic stimulation (COMS) therapy on wound-healing-related parameters, such as tissue oxygenation and water index, were analyzed by hyperspectral imaging: an exploratory case series. Background: Oedema and inadequate perfusion have been identified as key factors in delayed wound healing and have been linked to reduced mitochondrial respiration. Targeting mitochondrial dysfunction is a promising approach in the treatment of therapy refractory wounds. This sub-study aimed to investigate the effects of concurrent optical and magnetic stimulation (COMS) on oedema and perfusion through measuring tissue oxygenation and water index, using hyperspectral imaging. Patients and methods: In a multi-center, prospective, comparative clinical trial, eleven patients with chronic leg and foot ulcers were treated with COMS additively to Standard of Care (SOC). Hyperspectral images were collected during patient visits before and after treatment to assess short- and long-term hemodynamic and immunomodulatory effects through changes in tissue oxygenation and water index. Results: The average time for wound onset in the eleven patients analyzed was 183 days, with 64% of them being considered unresponsive to SOC. At week 12, the rate of near-complete and complete wound closure was 64% and 45%, respectively. COMS therapy with SOC resulted in an increased short-term tissue oxygenation over the 8-week treatment phase, with oxygen levels decreasing in-between patient visits. The study further found a decrease in tissue water content after the therapy, with a general accumulation of water levels in-between patient visits. This study’s long-term analysis was hindered by the lack of absolute values in hyperspectral imaging and the dynamic nature of patient parameters during visits, resulting in high interpatient and intervisit variability. Conclusions: This study showed that COMS therapy as an adjunct to SOC had a positive short-term effect on inflammation and tissue oxygenation in chronic wounds of various etiologies. These results further supported the body of evidence for safety and effectiveness of COMS therapy as a treatment option, especially for stagnant wounds that tended to stay in the inflammatory phase and required efficient phase transition towards healing. Full article
(This article belongs to the Special Issue Electromagnetic Regenerative Bioengineering: Updates and Future Directions)
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Review

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23 pages, 2271 KiB  
Review
Harmonizing Magnetic Mitohormetic Regenerative Strategies: Developmental Implications of a Calcium–Mitochondrial Axis Invoked by Magnetic Field Exposure
by Alfredo Franco-Obregón
Bioengineering 2023, 10(10), 1176; https://doi.org/10.3390/bioengineering10101176 - 10 Oct 2023
Cited by 10 | Viewed by 6217
Abstract
Mitohormesis is a process whereby mitochondrial stress responses, mediated by reactive oxygen species (ROS), act cumulatively to either instill survival adaptations (low ROS levels) or to produce cell damage (high ROS levels). The mitohormetic nature of extremely low-frequency electromagnetic field (ELF-EMF) exposure thus [...] Read more.
Mitohormesis is a process whereby mitochondrial stress responses, mediated by reactive oxygen species (ROS), act cumulatively to either instill survival adaptations (low ROS levels) or to produce cell damage (high ROS levels). The mitohormetic nature of extremely low-frequency electromagnetic field (ELF-EMF) exposure thus makes it susceptible to extraneous influences that also impinge on mitochondrial ROS production and contribute to the collective response. Consequently, magnetic stimulation paradigms are prone to experimental variability depending on diverse circumstances. The failure, or inability, to control for these factors has contributed to the existing discrepancies between published reports and in the interpretations made from the results generated therein. Confounding environmental factors include ambient magnetic fields, temperature, the mechanical environment, and the conventional use of aminoglycoside antibiotics. Biological factors include cell type and seeding density as well as the developmental, inflammatory, or senescence statuses of cells that depend on the prior handling of the experimental sample. Technological aspects include magnetic field directionality, uniformity, amplitude, and duration of exposure. All these factors will exhibit manifestations at the level of ROS production that will culminate as a unified cellular response in conjunction with magnetic exposure. Fortunately, many of these factors are under the control of the experimenter. This review will focus on delineating areas requiring technical and biological harmonization to assist in the designing of therapeutic strategies with more clearly defined and better predicted outcomes and to improve the mechanistic interpretation of the generated data, rather than on precise applications. This review will also explore the underlying mechanistic similarities between magnetic field exposure and other forms of biophysical stimuli, such as mechanical stimuli, that mutually induce elevations in intracellular calcium and ROS as a prerequisite for biological outcome. These forms of biophysical stimuli commonly invoke the activity of transient receptor potential cation channel classes, such as TRPC1. Full article
(This article belongs to the Special Issue Electromagnetic Regenerative Bioengineering: Updates and Future Directions)
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