Pulsed Electromagnetic Field Stimulation Research Articles

Efficiency of pulsed electromagnetic field and neuromuscular electrical stimulation on painful shoulder following stroke

Efficiency of pulsed electromagnetic field and neuromuscular electrical stimulation on painful shoulder following stroke

Adjunctive Use of Bone Growth Stimulation Increases Cervical Spine Fusion Rates in Patients at Risk for Pseudarthrosis.

A prospective multicenter clinical trial (NCT03177473) was conducted with a retrospective cohort used as a control arm. The purpose of this study was to evaluate cervical spine fusion rates in subjects with risk factors for pseudarthrosis who received pulsed electromagnetic field (PEMF) treatment. Certain risk factors predispose patients to pseudarthrosis, which is associated with prolonged pain, reduced function, and decreased quality of life. Subjects in the PEMF group were treated with PEMF for 6 months postoperatively. The primary outcome measure was fusion status at the 12-month follow-up period. Fusion status was determined using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). A total of 213 patients were evaluated (PEMF, n=160; Control, n=53). At baseline, the PEMF group had a higher percentage of subjects who used nicotine (P=0.01), had osteoporosis (P<0.05), multi-level disease (P<0.0001), and were >65 years of age (P=0.01). The PEMF group showed over two-fold higher percentage of subjects that had ≥3 risk factors (n=92/160, 57.5%) compared with the control group (n=14/53, 26.4%). At the 12-month follow-up, the PEMF group demonstrated significantly higher fusion rates compared with the control (90.0% vs. 60.4%, P<0.05). A statistically significant improvement in fusion rate was observed in PEMF subjects with multi-level surgery (P<0.0001) and high BMI (>30kg/m2; P=0.0021) when compared with the control group. No significant safety concerns were observed. Adjunctive use of PEMF stimulation provides significant improvements in cervical spine fusion rates in subjects having risk factors for pseudarthrosis. When compared with control subjects that did not use PEMF stimulation, treated subjects showed improved fusion outcomes despite being older, having more risk factors for pseudarthrosis, and undergoing more complex surgeries.

1085 Adjunctive Use of Bone Growth Stimulation in Cervical Spine Fusion in Patients at Risk for Nonunion

INTRODUCTION: Prior failed fusion, multi-level disease, diabetes, nicotine usage, and osteoporosis are factors associated with nonunion, leading to prolonged pain, reduced function, and overall decreased quality of life. Previous studies have shown that pulsed electromagnetic field (PEMF) stimulation can improve fusion rates, particularly in subjects at risk for nonunion. METHODS: Data from a multi-center prospective study of subjects that underwent cervical spine fusion and were treated with PEMF was compared to a “matched” retrospective cohort that had fusion but were not treated with PEMF. The prospective cohort was enrolled based on having 1 or more of the following risk factors for nonunion: prior failed cervical spine fusion, multilevel fusion, diabetes, osteoporosis, or nicotine use. Fusion was assessed at 12 months postop using x-rays and/or CT. A cohort of cervical spine fusion patients that were prescribed PEMF, but did not receive PEMF treatment (e.g., insurance denial) were compared to PEMF treated subjects. RESULTS: At baseline, subjects in the PEMF treated group had a significantly higher average number of risk factors for nonunion (1.8 for treated group vs. 1.1 for control, p &lt; 0.001), and significantly higher average number of surgical levels (2.8 for treated group vs. 2.0 for control, p &lt; 0.005). At 12 months post-op, subjects in the PEMF group (n = 161) had a 90.1% fusion rate, compared to a 65.4% for the control group (n = 26) (p &lt; 0.001). CONCLUSIONS: PEMF stimulation provides significant improvements in cervical spine fusion rates in subjects having risk factors for nonunion. Compared to control subjects, PEMF treated subjects had improved fusion outcomes despite being older, having more risk factors for pseudarthrosis, and undergoing more complex surgeries.

173 Electrical Stimulation Used as an Adjunct to Cervical Spine Fusion in Patients at Risk for Pseudarthrosis

INTRODUCTION: Prior studies show that pulsed electromagnetic field (PEMF) stimulation promotes bone healing and can be a valuable tool to help overcome biological deficiencies in patients at risk. The current study further evaluates the adjunct effect of PEMF in subjects undergoing cervical spinal surgery presenting with risk factors for pseudarthrosis. METHODS: A prospective multicenter clinical trial (NCT 03177473) was conducted at eleven clinical sites. Subjects undergoing cervical spinal fusion surgery with one or more risk factors for pseudarthrosis were identified for enrollment. Risk factors for pseudarthrosis included multilevel fusion, prior failed cervical spine fusion, diabetes, osteoporosis, or smoking. Subjects undergoing cervical spinal fusion were required to wear the PEMF device for 4 hours/day for 6 months post-op. Fusion status was determined at the 12-month visit using anterior/posterior, lateral, and flexion/extension radiographs and computed tomography (without contrast). NDI, EQ-5D, SF-36, and VAS for neck and arm pain were collected as secondary outcome measures. RESULTS: Out of 160 subjects, 144 (90.0%) were graded as fused (all levels) at the 12-month visit. Fusion success was 91.7% (n = 55/60), 89.0% (n = 89/100), and 90.9% (n = 20/22) for subjects with 1, 2+, or 3+ risk factors, respectively. Significant improvements in NDI, SF-36, EQ-5D, VAS-arm and VAS-neck were observed compared to baseline (p &lt; 0.001). A device compliance rate of 85.0% was observed at 3-months and 78.3% at 6-months in subjects who had successful cervical fusion. CONCLUSIONS: The PEMF bone growth stimulator device is a valuable tool to aid in fusion healing, especially in challenging populations. Subjects in this study experienced favorable fusion rates of 90% and significant improvement in patient reported outcomes despite having elevated comorbidity and/or complex surgeries.

Investigation of the effectiveness of intermittent electromagnetic field stimulation for early internal cartilaginous ossification in prechondrocytic ATDC5 cells.

Pulsed electromagnetic field (PEMF) stimulation has been widely applied clinically to promote bone healing; however, its detailed mechanism of action, particularly in endochondral ossification, remains elusive, and long-term stimulation is required for its satisfactory effect. The aim of this study was to investigate the involvement of the mammalian target of rapamycin (mTOR) pathway in chondrocyte differentiation and proliferation using a mouse prechondroblast cell line (ATDC5), and establish an efficient PEMF stimulation strategy for endochondral ossification. The changes in cell differentiation (gene expression levels of aggrecan, type II collagen, and type X collagen) and proliferation (cellular uptake of bromodeoxyuridine [BrdU]) in ATDC5 cells in the presence or absence of rapamycin, an mTOR inhibitor, was measured. The effects of continuous and intermittent PEMF stimulation on changes in cell differentiation and proliferation were compared. Rapamycin significantly suppressed the induction of cell differentiation markers and the cell proliferation activity. Furthermore, only intermittent PEMF stimulation continuously activated the mTOR pathway in ATDC5 cells, significantly promoting cell proliferation. These results demonstrate the involvement of the mTOR pathway in chondrocyte differentiation and proliferation and suggest that intermittent PEMF stimulation could be effective as a stimulus for endochondral ossification during fracture healing process, thereby reducing stimulationtime.

Secretome from Magnetically Stimulated Muscle Exhibits Anticancer Potency: Novel Preconditioning Methodology Highlighting HTRA1 Action.

Briefly (10 min) exposing C2C12 myotubes to low amplitude (1.5 mT) pulsed electromagnetic fields (PEMFs) generated a conditioned media (pCM) that was capable of mitigating breast cancer cell growth, migration, and invasiveness in vitro, whereas the conditioned media harvested from unexposed myotubes, representing constitutively released secretome (cCM), was less effective. Administering pCM to breast cancer microtumors engrafted onto the chorioallantoic membrane of chicken eggs reduced tumor volume and vascularity. Blood serum collected from PEMF-exposed or exercised mice allayed breast cancer cell growth, migration, and invasiveness. A secretome preconditioning methodology is presented that accentuates the graded anticancer potencies of both the cCM and pCM harvested from myotubes, demonstrating an adaptive response to pCM administered during early myogenesis that emulated secretome-based exercise adaptations observed in vivo. HTRA1 was shown to be upregulated in pCM and was demonstrated to be necessary and sufficient for the anticancer potency of the pCM; recombinant HTRA1 added to basal media recapitulated the anticancer effects of pCM and antibody-based absorption of HTRA1 from pCM precluded its anticancer effects. Brief and non-invasive PEMF stimulation may represent a method to commandeer the secretome response of muscle, both in vitro and in vivo, for clinical exploitation in breast and other cancers.

Unraveling the transcriptome profile of pulsed electromagnetic field stimulation in bone regeneration using a bioreactor-based investigation platform

IntroductionHuman mesenchymal stem cells (hMSCs) sense and respond to biomechanical and biophysical stimuli, yet the involved signaling pathways are not fully identified. The clinical application of biophysical stimulation including pulsed electromagnetic field (PEMF) has gained momentum in musculoskeletal disorders and bone tissue engineering. MethodologyWe herein aim to explore the role of PEMF stimulation in bone regeneration by developing trabecular bone-like tissues, and then, culturing them under bone-like mechanical stimulation in an automated perfusion bioreactor combined with a custom-made PEMF stimulator. After selecting the optimal cell seeding and culture conditions for inspecting the effects of PEMF on hMSCs, transcriptomic studies were performed on cells cultured under direct perfusion with and without PEMF stimulation. ResultsWe were able to identify a set of signaling pathways and upstream regulators associated with PEMF stimulation and to distinguish those linked to bone regeneration. Our findings suggest that PEMF induces the immune potential of hMSCs by activating and inhibiting various immune-related pathways, such as macrophage classical activation and MSP-RON signaling in macrophages, respectively, while promoting angiogenesis and osteogenesis, which mimics the dynamic interplay of biological processes during bone healing. ConclusionsOverall, the adopted bioreactor-based investigation platform can be used to investigate the impact of PEMF stimulation on bone regeneration.

Metabolomics comparison of metabolites and functional pathways in the SH-SY5Y cell model of Parkinson's disease under PEMF exposure

ObjectivePEMF is an emerging technique in the treatment of Parkinson's disease (PD) due to its potential improvement of movement speed. The aim of this study was to investigate the metabolic profiles of pulsed electromagnetic fields (PEMFs) in an SH-SY5Y cell model of PD. MethodsThe SH-SY5Y cell model of PD was induced by 1-methyl-4-phenylpyridinium (MPP+). Liquid chromatography mass spectrometry (LC‒MS)-based untargeted metabolomics was performed to examine changes in the PD cell model with or without PEMF exposure. We conducted KEGG pathway enrichment analysis to explore the potentially related pathways of the differentially expressed metabolites. ResultsA total of 275 metabolites were annotated, and 27 significantly different metabolites were found between the PEMF treatment and control groups (VIP >1, P < 0.05), mainly including 4 amino acids and peptides, 4 fatty acid esters, 2 glycerophosphoethanolamines, 2 ceramides and 2 monoradylglycerols; among them, 12 metabolites were upregulated, and 15 were downregulated. The increased expression levels of glutamine, adenosine monophosphate and taurine were highly associated with PEMF stimulation in the PD model. The enrichment results of differentially abundant metabolite functional pathways showed that biological processes such as the mTOR signaling pathway, PI3K-Akt signaling pathway, and cAMP signaling pathway were significantly affected. ConclusionPEMFs affected glutamine, adenosine monophosphate and taurine as well as their functional pathways in an in vitro model of PD. Further functional studies regarding the biological effect of these changes are required to evaluate the clinical efficacy and safety of PEMF treatment in PD.

IMMUNOMODULATORY POTENTIAL OF MAGNETICALLY ASSISTED CELL SHEET UNDER HYPOXIC ENVIRONMENTS UPON MAGNETIC STIMULATION

Common tendon injuries impair healing, leading to debilitation and an increased re-rupture risk. The impact of oxygen-sensing pathways on repair mechanisms, vital in regulating inflammation and fibrosis, remains unclear despite their relevance in tendon pathologies. Recent studies show that pulsed electromagnetic field (PEMF) reduce inflammation in human tendon cells (hTDCs) and in hypoxia-induced inflammation. We investigated the hypoxia's impact (1% and 2% oxygen tension) using magnetic cell sheet constructs (IL-1β-magCSs) primed with IL-1β. IL-1β-magCSs were exposed to low OT (1h, 4h,6h) in a hypoxic chamber. To confirm the role of PEMF (5Hz, 4mT, 50% duty cycle) on hypoxia modulation, IL-1β-magCSs, previously exposed to OT, were 1h-stimulated with PEMF. Our results show a significant increase in HIF- 1a and HIF-2a expression on IL-1β-magCSs after exposure to 2%-OT at all time points, compared to 1%- OT and normoxia. TNFa, IL-6, and IL-8 expression increased after 6 hours of 1%-OT exposure. PEMF stimulation of hypoxic IL-1β-magCSs led to decreased pro-inflammatory genes and increased anti-inflammatory (IL-4,IL-10) expression compared to unstimulated magCSs. IFN-g, TNF-α, and IL-6 release increased after 6 hours, regardless of %-OT, while IL-10 levels tended to rise after PEMF stimulation at 2%-OT. Also, NFkB expression was increased on IL-1β-magCSs exposed to 4 h and 6 h of 2%-OT, suggesting a link between NFkB and the production of pro-inflammatory factors. Moreover, PEMF stimulation showed a significantly decreased NFkB level in IL-1β-magCSs.Overall, low OT enhances expression of hypoxia-associated genes and inflammatory markers in IL-1β-magCSs with the involvement of NFkB. PEMF modulates the response of magCSs, previously conditioned to hypoxia and to inflammatory triggers, favouring expression of anti-inflammatory genes and proteins, supporting PEMF impact in pro-regenerative tendon strategies.Acknowledgements: ERC CoG MagTendon(No.772817), FCT under the Scientific Employment Stimulus-2020.01157.CEECIND. Thanks to Hospital da Prelada for providing tendon tissue samples (Portugal), and TERMRES Hub (Norte-01-0145-FEDER-022190).

Pulsed electromagnetic field stimulation enhances neurite outgrowth in neural cells and modulates inflammation in macrophages

Nerve regeneration following traumas remains an unmet challenge. The application of pulsed electromagnetic field (PEMF) stimulation has gained traction for a minimally invasive regeneration of nerves. However, a systematic exploration of different PEMF parameters influencing neuron function at a cellular level is not available. In this study, we exposed neuroblastoma F11 cells to PEMF to trigger beneficial effects on neurite outgrowth. Different carrier frequencies, pulse repetition frequencies, and duty cycles were screened with a custom ad hoc setup to find the most influential parameters values. A carrier frequency of 13.5 MHz, a pulse repetition frequency of 20 Hz, and a duty cycle of 10% allowed maximal neurite outgrowth, with unaltered viability with respect to non-stimulated controls. Furthermore, in a longer-term analysis, such optimal conditions were also able to increase the gene expression of neuronal expression markers NeuN and Tuj-1 and transcription factor Ngn1. Finally, the same optimal stimulation conditions were also applied to THP-1 macrophages, and both pro-inflammatory (TNF-α, IL-1β, IL-6, IL-8) and anti-inflammatory cytokines (IL-10, CD206) were analyzed. The optimal PEMF stimulation parameters did not induce differentiation towards an M1 macrophage phenotype, decreased IL-1β and IL-8 gene expression, decreased TNF-α and IL-8 cytokine release in M1-differentiated cells, increased IL-10 and CD206 gene expression, as well as IL-10 cytokine release in M0 cells. The specific PEMF stimulation regime, which is optimal in vitro, might have a high potential for a future in vivo translation targeting neural regeneration and anti-inflammatory action for treating peripheral nerve injuries.

Low-frequency pulsed electromagnetic fields alleviate the condylar cartilage degeneration and synovitis at the early stage of temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is characterized by articular cartilage degeneration and progressive synovitis. How to effectively inhibit TMJOA in the early stage has been a hot topic in the biomedical field. As a non-invasive physiotherapy, pulsed electromagnetic field (PEMF) treatment has shown great potential in the treatment of osteoarthritis (OA) in extremity joints. This study aims to investigate the biological effect of PEMF intervention on TMJ cartilage degeneration and synovium inflammation at the early stage of TMJOA. PEMF (2.0 mT, 15 Hz, 2 h/day) treatment was given to rats in which TMJOA was induced by applying the unilateral anterior crossbite (UAC). Histological and immunohistochemical staining, TUNEL assay, real-time PCR and western blotting assay were performed to detect the changes of the morphology and the expression of pro-inflammatory and degradative factors in condylar cartilage and synovium. Obvious condylar cartilage degeneration, characterized by decreased cartilage thickness, degraded cartilage extracellular matrix, increased expression of pro-inflammatory and degradative factors (TNF-α, IL-1β, MMP-13, ADAMTS-5, IL-6, MMP-3, MMP-9 and COL-X) and increased chondrocytes death, was observed in UAC group, accompanied by synovium hyperplasia and up-regulation of pro-inflammatory and degradative factors in synovium. PEMF intervention reversed the decreased cartilage thickness at 3 weeks and degraded cartilage extracellular matrix at 6 weeks. Moreover, the up-regulation of pro-inflammatory, degradative and hypertrophyic factors and chondrocytes death in condylar cartilage induced by UAC were inhibited to some extent. In addition, the synovium hyperplasia and the up-regulation of pro-inflammatory and degradative factors in synovium were inhibited at 3 weeks and 6 weeks. Appropriate PEMF stimulation can reverse the loss of cartilage extracellular matrix, the chondrocytes death, the increased expression of pro-inflammatory and degradative factors in cartilage, the decreased cartilage thickness and synovium inflammation induced by UAC at the early stage of TMJOA to some extent. PEMF stimulation may be a promising method in clinical TMJOA treatment.

Pulsed Electromagnetic Field Stimulation in Lumbar Spine Fusion for Patients With Risk Factors for Pseudarthrosis.

Lumbar spinal fusion surgeries are increasing steadily due to an aging and ever-growing population. Patients undergoing lumbar spinal fusion surgery may present with risk factors that contribute to complications, pseudarthrosis, prolonged pain, and reduced quality of life. Pulsed electromagnetic field (PEMF) stimulation represents an adjunct noninvasive treatment intervention that has been shown to improve successful fusion and patient outcomes following spinal surgery. A prospective, multicenter study investigated PEMF as an adjunct therapy to lumbar spinal fusion procedures in patients at risk for pseudarthrosis. Patients with at least 1 of the following risk factors were enrolled: prior failed fusion, multilevel fusion, nicotine use, osteoporosis, or diabetes. Fusion status was determined by radiographic imaging, and patient-reported outcomes were also evaluated. A total of 142 patients were included in the analysis. Fusion status was assessed at 12 months follow-up where 88.0% (n = 125/142) of patients demonstrated successful fusion. Fusion success for patients with 1, 2+, or 3+ risk factors was 88.5%, 87.5%, and 82.3%, respectively. Significant improvements in patient-reported outcomes using the Short Form 36, EuroQol 5 Dimension (EQ-5D) survey, Oswestry Disability Index, and visual analog scale for back and leg pain were also observed compared with baseline scores (P < 0.001). A favorable safety profile was observed. PEMF treatment showed a positive benefit-risk profile throughout the 6-month required use period. The addition of PEMF as an adjunct treatment in patients undergoing lumbar spinal surgery provided a high rate of successful fusion with significant improvements in pain, function, and quality of life, despite having risk factors for pseudarthrosis. PEMF represents a useful tool for adjunct treatment in patients who have undergone lumbar spinal surgery. Treatment with PEMF may result in improved fusion and patient-reported outcomes, regardless of risk factors. NCT03176303.

Postoperative Rehabilitation to Improve Outcomes After Cervical Spine Fusion for Degenerative Cervical Spondylosis: A Systematic Review.

Postoperative rehabilitation has recently been identified as a high-priority research topic for improving surgical outcomes for degenerative cervical spondylosis (DCS). However, there remains no consensus on specific rehabilitation strategies. Thus, the objective of this study was to evaluate the effectiveness of postoperative rehabilitation strategies for short-term and long-term outcomes after cervical spine fusion forDCS. A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines using the PubMed, Scopus, and Ovid Medline databases. All level I-IV therapeutic studies in the English language investigating the outcomes of postoperative rehabilitation strategies after cervical spine fusion for DCS were included. Nine studies with 895 patients with DCS (747 anterior-only fusion, 55 patients with posterior-only fusion, 93 patients with physiotherapy alone) were included in this analysis, with 446 (49.8%) patients receiving physiotherapy alone or standard postoperative therapyand 449 (50.2%) patients receiving standard postoperative therapy with additional intervention or augmentation. These interventions included pulsed electromagnetic field (PEMF) stimulation, telephone-supported home exercise program (HEP), early cervical spine stabilizer training, structured postoperative therapy, and a postoperative cervical collar. One level II study demonstrated that PEMF led to increased fusion rates at six months postoperatively compared to standard therapy alone, one level II study demonstrated that postoperative cervical therapy in addition to standard therapy was better than standard therapy alone in the improvement of neck pain intensity, one level IV study demonstrated home exercise therapy led to an improvement in neck pain, arm pain, and disability, and six level II studies reported no difference in clinical outcome measures between augmented or targeted therapy and standard postoperative therapy for DCS. In conclusion, there is moderate evidence to suggest that there is no significant difference in clinical and surgical outcomes between standard postoperative therapy and augmented or targeted postoperative therapy for cervical fusion in the setting of cervical spondylosis. However, there is some evidence to support that certain therapeutic modalities, such as PEMF stimulation, may lead to improved fusion rates, clinical outcomes, and patient satisfaction when compared to standard postoperative therapy protocols. There is no evidence to support a difference in effectiveness with different types of postoperative rehabilitation strategies between anterior and posterior fusions for DCS.

Stimulasi Pulsed Electromagnetic Field (PEMF) pada Osteogenesis Pergerakan Gigi Ortodonti

The prevalence of malocclusion and the need for orthodontic treatment in Indonesia is relatively very high. Orthodontic treatment that transmits mechanical forces to the periodontal ligament and alveolar bone cells can stimulate the periodontal ligament and alveolar bone remodeling. While this time, orthodontic treatment requires a long time, resulting in several adverse effects and discomfort. For this reason, a method that can accelerate orthodontic treatment is needed which aims to increase stability after active orthodontic treatment, to reduce the potential for relapse, and to accelerate retention time. Pulsed Electromagnetic Field (PEMF) stimulation is one of the methods that have this goal. This aim to study the stimulation mechanism of PEMF on the osteogenesis process of orthodontic tooth movement. Alveolar bone remodeling played an essential role in orthodontic tooth movement, is an active and dynamic process. The dynamic process depends on a balance between resorption and bone formation (osteogenesis). PEMF stimulation is a nonsurgical method that can promote osteogenesis through activation of Wnt signaling. Several studies showed that this method could accelerate retention time and orthodontic treatment. PEMF stimulated osteogenesis through activation of Wnt signaling in orthodontic tooth movement.

Effect of Pulsed Electromagnetic Fields (PEMFs) on Muscular Activation during Cycling: A Single-Blind Controlled Pilot Study.

PEMF stimulation results in a higher O2 muscle supply during exercise through increased O2 release and uptake. Given the importance of oxygen uptake in sport activity, especially in aerobic disciplines such as cycling, we sought to investigate the influence of PEMF on muscle activity when subjects cycled at an intensity between low and severe. Twenty semi-professional cyclists performed a constant-load exercise with randomized active (ON) or inactive (OFF) PEMF stimulation. Each subject started the recording session with 1 min of cycling without load (warm-up), followed by an instantaneous increase in power, as the individualized workload (constant-load physical effort). PEMF loops were applied on the vastus medialis and biceps femoris of the right leg. We recorded the electromyographic activity from each muscle and measured blood lactate prior the exercise and during the constant-load physical effort. PEMF stimulation caused a significant increase in muscle activity in the warm-up condition when subjects cycled without load (p < 0.001). The blood lactate concentration was higher during PEMF stimulation (p < 0.001), a possible consequence of PEMF's influence on glycolytic metabolism. PEMF stimulation augmented the activity and the metabolism of muscular fibers during the execution of physical exercise. PEMF stimulation could be used to raise the amplitude of muscular responses to physical activity, especially during low-intensity exercise.

Electromagnetic investigation of neuron growth by using pulsed electromagnetic field stimulation

Electromagnetic field (EMF) applications for humans have been widely used for medical therapy for a long time. Various nerve diseases such as complex regional pain syndrome, cerebral palsy and spinal cord injuries may occur as a result of damage on the nerve cells. In addition, EMF applications are taken into consideration in terms of tissue regeneration. The use of electricity for nerve regeneration is applied internally or externally. The use of direct current (DC) electric fields to stimulate axon elongation and nerve regeneration in nerve cells has been applied in various studies. In our study, electromagnetic field was used for the controlled and directional growth of Dorsal Root Ganglia (DRG) nerve cells. An amplifier circuit, which can produce amplified signals to generate proposed pulsed electromagnetic fields (PEMF) is designed. The electromagnetic field is produced on FR-4 copper plate, which highlights electrical field unlike previous studies, since there is no circular coil structure preferred. The elongation of nerve cells is planned to be in one direction, hence the signal to be applied is produced as a novel asymmetrical waveform (sawtooth) in addition to triangular and square waveforms which were previously preferred in recent studies. By the aid of proposed novel construction and produced signal waveform, PEMF system can be applied for nerve diseases effectively. The morphological nerve cell elongation results and PEMF results have been investigated and the effectiveness of the proposed system is verified.

Effect of pulsed electromagnetic fields on mesenchymal stem cell-derived exosomes in inhibiting chondrocyte apoptosis

The study aims to explore the effect of mesenchymal stem cells-derived exosomes (MSCs-Exo) on staurosporine (STS)-induced chondrocyte apoptosis before and after exposure to pulsed electromagnetic field (PEMF) at different frequencies. The AMSCs were extracted from the epididymal fat of healthy rats before and after exposure to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. MSCs-Exo was extracted and identified. Exosomes were labeled with DiO fluorescent dye, and then co-cultured with STS-induced chondrocytes for 24 h. Cellular uptake of MSC-Exo, apoptosis, and the protein and mRNA expression of aggrecan, caspase-3 and collagenⅡA in chondrocytes were observed. The study demonstrated that the exposure of 75 Hz PEMF was superior to 15 and 45 Hz PEMF in enhancing the effect of exosomes in alleviating chondrocyte apoptosis and promoting cell matrix synthesis. This study lays a foundation for the regulatory mechanism of PEMF stimulation on MSCs-Exo in inhibiting chondrocyte apoptosis, and opens up a new direction for the prevention and treatment of osteoarthritis.

Pulsed Electromagnetic Field Therapy and Direct Current Electric Field Modulation Promote the Migration of Fibroblast-like Synoviocytes to Accelerate Cartilage Repair In Vitro.

Articular cartilage injuries are a common source of joint pain and dysfunction. As articular cartilage is avascular, it exhibits a poor intrinsic healing capacity for self-repair. Clinically, osteochondral grafts are used to surgically restore the articular surface following injury. A significant challenge remains with the repair properties at the graft-host tissue interface as proper integration is critical toward restoring normal load distribution across the joint. A key to addressing poor tissue integration may involve optimizing mobilization of fibroblast-like synoviocytes (FLS) that exhibit chondrogenic potential and are derived from the adjacent synovium, the specialized connective tissue membrane that envelops the diarthrodial joint. Synovium-derived cells have been directly implicated in the native repair response of articular cartilage. Electrotherapeutics hold potential as low-cost, low-risk, non-invasive adjunctive therapies for promoting cartilage healing via cell-mediated repair. Pulsed electromagnetic fields (PEMFs) and applied direct current (DC) electric fields (EFs) via galvanotaxis are two potential therapeutic strategies to promote cartilage repair by stimulating the migration of FLS within a wound or defect site. PEMF chambers were calibrated to recapitulate clinical standards (1.5 ± 0.2 mT, 75 Hz, 1.3 ms duration). PEMF stimulation promoted bovine FLS migration using a 2D in vitro scratch assay to assess the rate of wound closure following cruciform injury. Galvanotaxis DC EF stimulation assisted FLS migration within a collagen hydrogel matrix in order to promote cartilage repair. A novel tissue-scale bioreactor capable of applying DC EFs in sterile culture conditions to 3D constructs was designed in order to track the increased recruitment of synovial repair cells via galvanotaxis from intact bovine synovium explants to the site of a cartilage wound injury. PEMF stimulation further modulated FLS migration into the bovine cartilage defect region. Biochemical composition, histological analysis, and gene expression revealed elevated GAG and collagen levels following PEMF treatment, indicative of its pro-anabolic effect. Together, PEMF and galvanotaxis DC EF modulation are electrotherapeutic strategies with complementary repair properties. Both procedures may enable direct migration or selective homing of target cells to defect sites, thus augmenting natural repair processes for improving cartilage repair and healing.

The Effect of Different Frequencies of Pulsed Electromagnetic Fields on Cartilage Repair of Adipose Mesenchymal Stem Cell-Derived Exosomes in Osteoarthritis.

The intra-articular injection of mesenchymal stem cell (MSC)-derived exosomes has already been proved to reverse osteoarthritic cartilage degeneration. Pulsed electromagnetic field (PEMF) has been found to regulate the biogenic function of MSCs. However, the effect of PEMF on MSC-derived exosomes has not yet been characterized. The aim of this study was to elucidate the regulatory role of different frequencies of PEMF in promoting the osteoarthritic cartilage regeneration of MSC-derived exosomes. The adipose tissue-derived MSCs (AMSCs) were extracted from the epididymal fat of healthy rats and further exposed to the PEMF at 1 mT amplitude and a frequency of 15, 45, and 75 Hz, respectively, in an incubator. The chondrocytes were treated with interlukin-1β (IL-1β) and the regenerative effect of co-culturing with PEMF-exposed AMSC-derived exosomes was assessed via Western blot, quantitative polymerase chain reaction, and ELISA assays. A rat model of osteoarthritis was established by anterior cruciate ligament transection (ACLT) surgery and received 4 times intra-articular injection of PEMF-exposed AMSC-derived exosomes once a week. After 8 weeks, the knee joint specimens of rats were collected for micro-computed tomography and histologic analyses. PEMF-exposed AMSC-derived exosomes could be endocytosed with IL-1β-induced chondrocytes. Compared with the AMSC-derived exosomes alone, the PEMF-exposed AMSC-derived exosomes substantially suppressed the inflammation and extracellular matrix degeneration of IL-1β-induced chondrocytes as shown by higher expression of transcripts and proteins of COL2A1, SOX9, and ACAN and lower expression of MMP13 and caspase-1. Of these, the 75-Hz PEMF presented a more significant inhibitive effect than the 15-Hz and 45-Hz PEMFs. Furthermore, the intra-articular injection of 75-Hz PEMF-exposed exosomes could obviously increase the number of tibial epiphyseal trabeculae, lead to a remarkable decrease in Osteoarthritis Research Society International score, and upregulate the COL2A1 and ACAN protein level of the degenerated cartilage. The present study demonstrated that PEMF stimulation could effectively promote the regeneration effects of AMSC-derived exosomes on osteoarthritic cartilage. Compared with other frequency parameters, the PEMF at a frequency of 75 Hz showed a superior positive effect on AMSC-derived exosomes in suppressing the IL-1β-induced chondrocyte inflammation and extracellular matrix catabolism, as well as the osteoarthritic cartilage degeneration.

Effects of the Pulsed Electromagnetic Fields on Experimental Periodontitis and Estrogen Deficiency.

Periodontitis is an inflammatory disease resulting from a complex polymicrobial infection that causes tissue destruction in susceptible individuals. Osteoporosis has been associated with greater clinical attachment loss in patients with periodontitis. Experimental studies have shown positive results in the treatment of osteoporosis through pulsed electromagnetic field (PEMF) stimulation. The aim of this study was to evaluate the effects of PEMF in the presence of estrogen deficiency associated with periodontitis, verifying its role in bone metabolism and in the inflammatory response. Sixty rats were divided into four groups: Sham surgery + ligature-induced periodontitis (P); Sham surgery + ligature-induced periodontitis + PEMF therapy (P + PEMF); Ovariectomy surgery + ligature-induced periodontitis (P + OVX); Ovariectomy surgery + ligature-induced periodontitis + PEMF therapy (P + OVX + PEMF). The area of bone loss in the furcation region (BL), connective tissue attachment loss (CTAL) and alveolar bone loss (ABL), BV/TV and BMD were evaluated. In addition to immunohistochemical labelling of RANKL, OPG, and TRAP and the inflammatory response of interleukin (IL)-1b, IL-6, TNF-α, IL-10, and vascular endothelial growth factor. P + OVX showed significant BL in relation to P + PEMF and the greatest CTAL and ABL. P + OVX and P + OVX + PEMF showed a significant reduction in BV/TV (%). P and P + PEMF showed a significantly lesser amount of Tb.Sp (mm) while P + OVX and P + OVX + PEMF showed a lesser of Tb.N. P + PEMF had the greatest BMD. P + OVX presented higher RANKL and lower OPG immunolabeling than other groups. P + PEMF and P + OVX + PEMF showed a reduction on all biomarkers evaluated. The application of PEMF seems to attenuate the effects of bone loss in the presence of periodontitis and ovariectomy. © 2022 Bioelectromagnetics Society.