August 2026
Abstract
Highlights
What are the main findings?
- PEMF stimulation promotes tenocyte proliferation across acute inflammatory models and enhances wound closure capacity, with PEMFs significantly improving wound closure in IL-1β-treated cells under acute low-dose inflammation.
- PEMF effects on inflammatory mediators, including IL-6, IL-8, GM-CSF, CCL2 and CCL5, vary according to the intensity and duration of the inflammatory stimulus.
What is the implications of the main finding?
- PEMFs are likely to support tenocyte regenerative behaviour during acute or mild inflammatory phases, suggesting that an evaluation of the inflammatory status is a critical determinant of treatment efficacy.
Abstract
Tendinopathy is a prevalent musculoskeletal condition characterised by chronic inflammatory and degenerative changes. Pulsed electromagnetic fields (PEMFs) represent a promising biophysical therapeutic modality, yet their effects across different inflammatory states of tendinopathy remain poorly characterised. To evaluate PEMF biological effects on human tenocytes, three in vitro models differing in IL-1β dose and duration were tested: acute low-dose (0.1 ng/mL, 96 h), acute high-dose (1 ng/mL, 96 h), and prolonged (0.1 ng/mL, 9 days). At the transcriptional level, PEMFs significantly reduced IL-6 and IL-8 mRNA overexpression in the acute low-dose model and CCL2 upregulation in the prolonged model. At the secretome level, PEMFs reduced GM-CSF and IL-8 secretion in the acute high-dose model, and suppressed CCL2 and CCL5 protein secretion in the prolonged model. MMP activity was not modulated by PEMFs in any condition. PEMFs consistently increased tenocyte proliferation across both the acute models. Finally, in wound healing assays, non-inflamed tenocytes exposed to PEMFs showed significantly enhanced wound closure compared to IL-1β-treated cells across all models; in the acute low-dose model, PEMFs also significantly improved wound closure in IL-1β-treated cells at an early timepoint, whereas no such effect was observed in cells exposed to high-dose or prolonged inflammation. PEMFs exert context-dependent effects, promoting healing primarily during acute or mild inflammation. These findings suggest that the inflammatory stage of tenocytes may influence PEMF responsiveness in vitro, highlighting the importance of considering this variable in the design of future clinical studies evaluating PEMF therapy for tendinopathy.
1. Introduction
Tendinopathy is a spectrum of chronic tendon disorders affecting both the general population and athletes, characterised by persistent pain, localised swelling, and impaired function. The condition accounts for approximately 30% of referrals to musculoskeletal practitioners and represents a substantial socioeconomic burden [1]. Although historically classified as a degenerative disorder driven by mechanical overload and failed healing, increasing evidence has reframed tendinopathy as a disease with a significant inflammatory component, involving complex crosstalk between structural, cellular, and molecular mechanisms [2,3]. The transition from healthy to pathological tendon is characterised by extracellular matrix (ECM) disorganisation, hypercellularity, and a profound phenotypic shift in tenocytes, which lose their tenogenic identity and acquire a catabolic and pro-inflammatory profile [4,5].
Interleukin-1β (IL-1β) has emerged as a pivotal mediator in tendinopathy pathogenesis. This pro-inflammatory cytokine is upregulated in diseased tendon tissue and promotes a catabolic cascade in tenocytes, including upregulation of cyclooxygenase-2 (COX2), prostaglandin E2 (PGE2), and matrix metalloproteinases (MMPs), alongside downregulation of critical tenogenic transcription factors such as scleraxis (SCX) [4,6]. Moreover, IL-1β perpetuates inflammatory cycles through activation of NF-κB and MAPK signalling pathways, and has been implicated in the loss of tendon stem/progenitor cell identity [7].
Current conservative and surgical treatments for tendinopathy demonstrate limited efficacy, underscoring the need for novel therapeutic strategies. Pulsed electromagnetic fields (PEMFs) represent a non-invasive biophysical intervention with established applications in bone healing and increasing evidence supporting their role in soft tissue repair. In a previous study, our group demonstrate that in a rat model of collagenase-induced Achilles tendinopathy, daily PEMF exposure improved tendon fibre organisation and restored physiological tissue architecture, particularly when applied during the mid-acute phase of disease [8]. PEMFs are thought to modulate cellular behaviour through interactions with membrane-associated receptors, particularly A2A adenosine receptors, and the subsequent attenuation of pro-inflammatory signalling pathways [9,10]. In vitro studies in tenocytes have already demonstrated PEMF-mediated reductions in IL-6, IL-8, COX-2, and MMP expression, together with increased type I collagen synthesis [9,11,12].
Within the broader landscape of engineering strategies for musculoskeletal tissue regeneration, PEMFs represent a non-genetic approach to directing tenocyte behaviour through controlled physical stimulation, providing a complement to biomaterial and cell-based regenerative strategies.
However, a critical limitation of the existing studies is their reliance on single, acute inflammatory models, which fail to recapitulate the heterogeneity and the different stages of tendinopathy. Chronic tendinopathy encompasses distinct inflammatory phases, from acute reactive stages, characterised by rapid cytokine upregulation and acute ECM remodelling, to prolonged degenerative states associated with sustained low-grade inflammation and loss of tenogenic commitment, which may respond differently to biophysical stimulation [1,4]. No study to date has systematically compared PEMF effects across inflammatory models of varying dose and duration in human tenocytes.
The present study therefore aimed to comprehensively evaluate PEMF effects on human tenocytes using three distinct IL-1β-based inflammatory models encompassing inflammatory conditions ranging from acute to more sustained, prolonged stages of tendinopathy: an acute low-dose model, an acute high-dose model, and a prolonged model. PEMF effects were assessed in terms of gene expression profiles, secretion of inflammatory mediators, MMP activity, cell migration, and proliferation, with the overarching aim of defining the inflammatory context in which PEMF stimulation exerts the most relevant biological activity.
Continue Reading: https://pmc.ncbi.nlm.nih.gov/articles/PMC13565733/
