Aims:Hamstring tendons are commonly used autografts for anterior cruciate ligament (ACL) reconstruction. They represent an optimal source for in vitro testing of new approaches that may improve tendon regeneration and, likely, ligamentization after ACL reconstruction. We assessed ex vivo, in a 3D explant culture, the anabolic effect of pulsed electromagnetic fields (PEMF) on hamstring tendons in an experimental setting as close as possible to that of common clinical applications, suggesting a potential new therapeutic strategy to improving tendon remodelling. Methods:We exposed tendon explants from nine donors to PEMF for 21 days, eight hours/day, with an intensity similar to that used in clinical practice, and evaluated specific gene expression by immunofluorescence and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses. Results:Increased expression of tendon-related markers (scleraxis, collagen types I and VI) and important players of tenogenic differentiation (c-Fos and mammalian target of rapamycin) was evidenced by immunofluorescence analysis upon PEMF exposure and confirmed by qRT-PCR analysis. Conclusion:Our results demonstrate that PEMF enhances tendon differentiation, which suggests that PEMF exposure could have clinical relevance as a new non-invasive adjuvant treatment for improving the early phases of hamstring autograft remodelling after ACL reconstruction, as well as possibly for hastening the repair of injured tendons.

Complex regional pain syndrome type I (CRPS-I) is a condition characterised by pain, swelling, loss of function, trophic skin changes and vasomotor dysfunction. Biophysical stimulation with a specific combination of pulsed electromagnetic field (PEMF) parameters exerts an anti-inflammatory effect, supporting the rehabilitation process. We recruited 32 patients with CRPS-I of the foot or ankle, previously treated with an initial course of IV neridronate. Participants were randomised to one of two groups: a treatment programme combining PEMF (1.5 mT, 75 Hz; I-One® therapy, IGEA) for 4 h a day for 60 days and exercises for 30 min a day for 6 weeks (I-One® therapy group), or treatment with exercise only (control group). Patients were clinically assessed at 3, 6 and 12 months with: Visual Analogue Score (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score, allodynia, hyperalgesia, pain during passive range of motion (ROM), oedema, Roles and Maudsley scores and non-steroidal anti-inflammatory drug (NSAID) intake. In both groups, VAS was significantly reduced and AOFAS improved significantly compared with baseline at all follow-up points. The I-One® therapy group saw statistically significant improvements compared with the control group at all follow-up points, not only in terms of VAS and AOFAS scores, but also in the resolution of allodynia, hyperalgesia and pain during passive ROM. At 3 months, the I-One® therapy group also showed a significantly lower intake of NSAIDs. The I-One® therapy group showed better patient satisfaction outcomes, with significantly lower Roles and Maudsley scores compared with the control group at 6 and 12 months. I-One® therapy in association with a rehabilitation program may offer additional benefits in terms of pain reduction, functional recovery, oedema, allodynia and hyperalgesia resolution and NSAIDs use in CRPS-I of the foot and ankle. Trial registration: registered on the ClinicalTrials.gov platform (NCT05922618) on 6 August 2023. Level II, therapeutic study.

Pulsed Electromagnetic Fields (PEMF) are widely used, with excellent clinical outcomes. However, their mechanism of action has not yet been completely understood. The purpose of this review is to describe current observations on the mechanisms of PEMF, together with its clinical efficacy. Osteoblast responsiveness to PEMF is described on several scales, from the cell membrane to clinically relevant bone formation. PEMF has been shown to activate membrane adenosine receptors. The role of adenosine receptors in activating intracellular second messenger pathways, such as the canonical Wnt/β-catenin pathway and the mitogen-activated protein kinases (MAPK) pathway, is described. The responsiveness of osteoblasts and the synthesis of structural and signaling proteins constitute the role of PEMFs in promoting osteogenesis and bone matrix synthesis, and they are described. Multiple studies, ranging from observational and randomized to meta-analyses that investigate the clinical efficacy of PEMF, are described. This review presents a favorable conclusion on the clinical effects of PEMF while unlocking the “black box” of PEMF’s mechanism of action, thus improving confidence in the clinical utility of PEMF in bone repair.

Abstract Background Capacitively coupling electric fields (CCEF) is a method of non-invasive biophysical stimulation that enhances fracture repair and spinal fusion. This multicentre randomized controlled trial aimed to further examine the roles of CCEF in (1) the resolution of vertebral bone marrow oedema (VBME) using a follow-up MRI study and (2) pain relief, analgesic drug consumption and quality of life improvement in stimulated patients who were referred with acute vertebral fragility fractures (VFFs) compared to non-stimulated patients. Methods Between September 2016 and December 2019, patients who were referred to the spine centres that participated in this multicentre randomized clinical study with acute VFFs of type OF1 or OF2 were included in the present study. All the VFFs were conservatively managed according to Good Clinical Practice. Moreover, the patients were randomized into two groups: the CCEF group received, as an adjunct to the clinical study protocol, biophysical stimulation with a CCEF device (Osteospine, IGEA) for 8 h per day for 60 days, whereas the control group was treated according to the clinical study protocol. At baseline (T0), the 30-day follow-up (T1), the 60-day follow-up (T2), and the 6-month follow-up (T3), each patient underwent clinical evaluation using the Visual Analogue Scale (VAS) for Pain and the Oswestry Disability Index (ODI). Analgesic therapy with paracetamol 1000 mg tablets for 7 days—or longer, depending on the pain intensity—was performed; patients were required to report their paracetamol consumption on a specific sheet between study day 8 to 180 days of follow-up. MRI studies of the thoracolumbar spine were performed at 0 (T0), 30 (T1) and 60 days of follow-up (T2) using a 1.5-T MRI system in all of the centres that took part in the study. For each VBME area examined via MRI, the vertebral body geometry (i.e. anterior wall height/posterior wall height and vertebral kyphosis) were assessed. Results A total of 66 patients (male: 9, 13.63%; mean age: 73.15 years old) with 69 VFFs were included in the present study and randomized as follows: 33 patients were included in the control group and the remaining 33 patients were randomized into the CCEF group. In the CCEF group, good compliance with CCEF therapy was observed (adherence = 94%), and no adverse effects were recorded. In the stimulated patients, faster VBME resolution and significantly less vertebral body collapse during follow-up were observed compared to the control patients. Moreover, in the active group, faster pain reduction and improvement in the ODI mean score were observed. Stimulated patients also reported a significantly lower paracetamol consumption rate from the third follow-up after treatment until the 6-month follow-up. In terms of sex-related differences, in the CCEF group, VBME showed a faster resolution in male patients compared with females. Conclusion Biophysical stimulation with CCEF, as an adjunct to traditional conservative treatment, is a useful tool to hasten the VBME resolution process and prevent vertebral body deformation. These MRI findings also correlate with faster back pain resolution and quality of life improvement. From the third follow-up after treatment until the 6-month follow-up, stimulated patients reported a significantly lower paracetamol consumption than control patients, even though back pain and quality of life showed no significant differences between the two groups. Level of evidence II. Trial Registration Register: ClinicalTrials.gov, number: NCT05803681.

Background: Biophysical stimulation therapy, Pulsed Electromagnetic Fields (PEMFs) and Capacitively Coupled Electric Fields (CCEFs) have significantly increased in the last twenty years. Due to this, it is necessary to have clear information regarding their efficacy, therapeutic indications and expected objectives. Application fields: There is a unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue-healing process and the symptoms associated with this situation. Differently, but no less important, positive results were observed in the joint compartment, especially with regard to the inhibition of the inflammatory process. Good results for chondroprotection were obtained in vitro and after a surgical procedure. New studies have shown the effectiveness also in cases of osteoporosis. Conclusions: The effectiveness of PEMFs and CCEFs on the bone-healing process and on joint preservation in the orthopedic and traumatology fields has consolidated evidence in the literature. We have also found positive results for symptoms and patient compliance with rehabilitation therapies. Therefore, their notable applications can be envisaged in the fields of prosthetic surgery and sports medicine.

Tendon disorders often result in decreased muscle function and atrophy. Pulsed Electromagnetic Fields (PEMFs) have shown potential in improving tendon fiber structure and muscle recovery. However, the molecular effects of PEMF therapy on skeletal muscle, beyond conventional metrics like MRI or markers of muscle decline, remain largely unexplored. This study investigates the metabolic and structural changes in PEMF-treated muscle tissue using proteomics in a rat model of Achilles tendinopathy induced by collagenase. Sprague Dawley rats were unilaterally induced for tendinopathy with type I collagenase injection and exposed to PEMFs for 8 h/day. Gastrocnemius extracts from untreated or PEMF-treated rats were analyzed with LC-MS/MS, and proteomics differential analysis was conducted through label-free quantitation. PEMF-treated animals exhibited decreased glycolysis and increased LDHB expression, enhancing NAD signaling and ATP production, which boosted respiratory chain activity and fatty acid beta-oxidation. Antioxidant protein levels increased, controlling ROS production. PEMF therapy restored PGC1alpha and YAP levels, decreased by tendinopathy. Additionally, myosins regulating slow-twitch fibers and proteins involved in fiber alignment and force transmission increased, supporting muscle recovery and contractile function. Our findings show that PEMF treatment modulates NAD signaling and oxidative phosphorylation, aiding muscle recovery through the upregulation of YAP and PGC1alpha and increasing slow myosin isoforms, thus speeding up physiological recovery.

Foot and ankle injuries are common in many sports. One of the main athletes issues is the time for sport resumption after trauma. Recently, extensive efforts have been made to speed up the athletes’ return-to-sport and to prevent joint degeneration. Among the conservative treatment options, biophysical stimulation with pulsed electromagnetic fields (PEMFs) is listed. This narrative review aims to outline current applications of PEMFs in main foot and ankle sport-related injuries, in particular in the treatment of bone marrow edema, osteochondral defects, fractures, and nonunions. Despite further high-quality studies on foot and ankle injuries are needed, PEMFs seem to be a valid aid to enhance the endogenous osteogenesis, to resolve the bone marrow edema, to inhibit the joint inflammation, preserving articular cartilage degeneration, and to relieve pain.

Phalangeal fractures are common events among the upper limbs accounting for 10% of all human body fractures. Fracture complete healing process may persevere several months or years. Most phalangeal fractures present favorable union within 3 to 6 weeks. In the literature, biophysical stimulation has yielded favorable outcomes in the treatment of hand fractures. A survey involving hospitals in the US reported the use of biophysical stimulation (72%) in relation to nonhealing fractures at three months after trauma. A noninvasive procedure such as biophysical stimulation may be preferential prior to consideration of invasive procedures. In this retrospective study, we analyzed 80 phalangeal fractures, 43 of which did not show any radiographic sign of healing 30 days after surgery; on radiograms, we calculated radiographic data and the total active motion (TAM) for clinical comparison. All radiographic images were evaluated using Adobe Photoshop CS3 (version 10.0, Adobe Systems Inc., San Jose, CA, USA). We calculated the index of relative bone healing each month after surgery starting from 30 days, which was considered as T1, and followed up for a total of 6 months after stimulation (T6) with better results in stimulated groups. We concluded that prompt administration of biophysical stimulation supports fracture healing and yields an important improvement in the union rate compared with nontreatment. Above all, our patients experienced less injury-related distress between the fracture and repair period, which consequently reduced immobilization time, envisaging an early rehabilitation interval, with a better patient hand outcome.

Background: To assess pain relief and clinical outcomes in patients undergoing unicompartmental knee arthro-plasty (UKA) stimulated with pulsed electromagnetic fields (PEMFs) compared to a control group.Methods: A prospective randomised controlled trial (RCT) was performed in which 72 patients undergoing medial UKA were randomised into a control group or an experimental PEMFs group. The patients allocated to the experimental group were instructed to use PEMFs for 4 h per day for 60 days. They were evaluated before a surgery and then during the time points corresponding to 1 month, 2 months, 6 months, 12 months, and 36 months after the surgery. No placebo group was included in the RCT. Clinical assessment included the Visual Analogue Scale (VAS) for pain, Oxford Knee Score (OKS), the Short Form 36 (SF-36) health survey questionnaire, and joint swelling. During each follow-up visit, the consumption of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) was recorded.Results: The VAS decreased on follow-up visits in both the groups; a statistically significant difference between the groups was observed during the 6 (p = 0.0297), 12 (p = 0.0003), and 36 months (p = 0.0333) follow-ups in favour of the PEMFs group. One month after UKA, the percentages of patients using NSAIDs in the PEMFs and control group were 71% and 92%, respectively (p = 0.0320). At the 2 months point, 15% of the patients in the PEMFs group used NSAIDs compared to 39% in the control group (p = 0.0317). The objective knee girth evaluation showed a statistically significant difference at 6 (p = 0.0204), 12 (p = 0.0005), and 36 (p = 0.0005) months with improved values observed in the PEMFs group. The subjective assessment of the swelling demon-strated a statistically significant difference at 2 (p = 0.0073), 6 (p = 0.0006), 12 (p = 0.0001), and 36 (p = 0.0011) months with better values noted in the PEMFs group. Last, the OKS result was significant higher in the experimental group during all the follow-ups (1mth: p = 0.0295; 2mths: p = 0.0012; 6mths: p = 0.0001; 12mths: p < 0.0001; 36mths: p = 0.0061).Conclusions: The use of PEMFs leads to significant pain relief, better clinical improvement, and lower NSAIDs consumption after medial UKA when compared to the control group.Level of evidence: II.

In recent years, applications regarding the use of Pulsed ElectroMagnetic Fields (PEMFs) have been growing thanks to important therapeutic implications found through in vitro and in vivo experiments. Experimental results converge in identifying a transmembrane receptor, e.g., the adenosine receptor A(2A), as a potential target for PEMFs application. This family of receptors plays a central role in a broad range of physiological processes which has made them important targets for structural biology. However, in silico modeling of this important receptor in presence of an external magnetic field is lacking. This paper provides an analysis for global and local molecular effects, especially for two main residues implicated in the so-called salt bridge interaction, that occurs in the extracellular part of the receptor when a static magnetic field with 1 T in intensity is applied.

It is estimated that approximately 5% to 10% of fractures will evolve into nonunions. Nonunions have a significant impact on patient quality of life and on socioeconomic costs. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive therapy widely used within the orthopedic community to accelerate the healing of fresh fractures, to minimize delayed healing, and to promote healing of nonunions. In this case series, 46 nonunions and 19 fresh fractures were treated with LIPUS for at least three months or until fracture healing. Bone healing was assessed both at a radiological and a functional level. Of the nonunions healed, 89% had a mean healing time of 89 ± 53 days. In the group of fresh fractures, the healing percentage was 95% with a mean healing time of 46 ± 28 days. LIPUS treatment is proven to be safe and well tolerated; there were no adverse events related to the use of the device, even in the presence of internal fixations and infections. LIPUS therapy should be considered a low-risk option both as an adjunct to surgery or as a standalone therapy in the management of nonunion and fresh fractures.

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.

Osteoarthritis (OA) is the most prevalent degenerative joint disease and the main cause of pain and disability in elderly people. OA currently represents a significant social health problem, since it affects 250 million individuals worldwide, mainly adults aged over 65. Although OA is a multifactorial disease, depending on both genetic and environmental factors, it is reported that joint degeneration has a higher prevalence in former athletes. Repetitive impact and loading, joint overuse and recurrent injuries followed by a rapid return to the sport might explain athletes’ predisposition to joint articular degeneration. In recent years, however, big efforts have been made to improve the prevention and management of sports injuries and to speed up the athletes’ return-to-sport. Biophysics is the study of biological processes and systems using physics-based methods or based on physical principles. Clinical biophysics has recently evolved as a medical branch that investigates the relationship between the human body and non-ionizing physical energy. A physical stimulus triggers a biological response by regulating specific intracellular pathways, thus acting as a drug. Preclinical and clinical trials have shown positive effects of biophysical stimulation on articular cartilage, subchondral bone and synovia. This review aims to assess the role of pulsed electromagnetic fields (PEMFs) and extracorporeal shockwave therapy (ESWT) in the prevention and treatment of joint degeneration in athletes.

Pulsed electromagnetic fields (PEMFs) are emerging as an innovative, non-invasive therapeutic option in different pathological conditions of the central nervous system, including cerebral ischemia. This study aimed to investigate the mechanism of action of PEMFs in an in vitro model of human astrocytes, which play a key role in the events that occur following ischemia. 1321N1 cells were exposed to PEMFs or hypoxic conditions and the release of relevant neurotrophic and angiogenic factors, such as VEGF, EPO, and TGF-β1, was evaluated by means of ELISA or AlphaLISA assays. The involvement of the transcription factor HIF-1α was studied by using the specific inhibitor chetomin and its expression was measured by flow cytometry. PEMF exposure induced a time-dependent, HIF-1α-independent release of VEGF from 1321N1 cells. Astrocyte conditioned medium derived from PEMF-exposed astrocytes significantly reduced the oxygen-glucose deprivation-induced cell proliferation and viability decrease in the neuron-like cells SH-SY5Y. These findings contribute to our understanding of PEMFs action in neuropathological conditions and further corroborate their therapeutic potential in cerebral ischemia.

Background: Lumbar spinal fusion (LSF) is used to treat lumbar degenerative disorders. Methods to improve the functional recovery of patients undergoing LSF is one of the main goals in daily clinical practice. The objective of this study is to assess whether biophysical stimulation with capacitively coupled electric fields (CCEF) can be used as adjuvant therapy to enhance clinical outcome in LSF-treated patients. Methods: Forty-two patients undergoing LSF were assessed and randomly allocated to either the active or to the placebo group. Follow-up visits were performed at 1, 3, 6, and 12 months after surgery; long-term follow-up was performed at year 10. Visual analogue scale (VAS), the Oswestry Disability Index (ODI), and the 36-item Short Form Health Survey (SF-36) questionnaire were recorded. Results: This study demonstrates a significant improvement in CCEF-treated patients at 6 and 12 months' follow-up for SF-36, and at 12 months' follow-up for ODI values. Based on SF-36 and ODI scores, we reported a significantly higher percentage of successful treatments at 12 months in the active compared with the placebo group. Moreover, in a subset of patients at 10 years' follow-up, a significant difference was reported in VAS and ODI scores between groups. Conclusions: The results demonstrate that 3 months of CCEF treatment immediately after surgery is effective in reducing ODI and improving SF-36 score, and that these benefits can be maintained up to 12 months. In a subset of patients, these positive outcomes are retained up to 10 years.

Neuroprotective effects of pulsed electromagnetic fields (PEMFs) have been demonstrated both in vivo and in vitro. Moreover, preliminary clinical studies have been conducted and suggested PEMFs as a possible alternative therapy to treat acute ischemic stroke. In this work, we show that it's possible to build-up a patient semi-specific head model, where the 3D reconstruction of the ischemic lesion of the patient under treatment is inserted in the head of the human body model "Duke" (v.1.0, Zurich MedTech AG). The semi-specific model will be used in the randomized, placebo-controlled, double-blind study currently ongoing. Three patients were modelled and simulated, and results showed that each ischemic lesion experiences a magnetic flux density field comparable to the one for which biological effects have been attested. Such a kind of dosimetric analysis reveals a reliable tool to assess the correlation between levels of exposure and the beneficial effect. Thus, once the on-going double blind study is complete it will prove if PEMFs treatment triggers a clinical effect, and we will then be able to characterize a dose-response curve with the methodology arranged in this study.

Although the rate of patients reporting satisfaction is generally high after joint replacement surgery, up to 23% after total hip replacement and 34% after total knee arthroplasty of treated subjects report discomfort or pain 1 year after surgery. Moreover, chronic or subacute inflammation is reported in some cases even a long time after surgery. Another open and debated issue in prosthetic surgery is implant survivorship, especially when related to good prosthesis bone ingrowth. Pulsed Electro Magnetic Fields (PEMFs) treatment, although initially recommended after total joint replacement to promote bone ingrowth and to reduce inflammation and pain, is not currently part of usual clinical practice. The purpose of this review was to analyze existing literature on PEMFs effects in joint replacement surgery and to report results of clinical studies and current indications. We selected all currently available prospective studies or RCT on the use of PEMFs in total joint replacement with the purpose of investigating effects of PEMFs on recovery, pain relief and patients' satisfaction following hip, knee or shoulder arthroplasty. All the studies analyzed reported no adverse effects, and good patient compliance to the treatment. The available literature shows that early control of joint inflammation process in the first days after surgery through the use of PEMFs should be considered an effective completion of the surgical procedure to improve the patient's functional recovery.