Cartilage chondroprotection and repair with pulsed electromagnetic fields: I-ONE therapy |
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Authors: | Ruggero Cadossi Stefania Setti Milena Fini |
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Institution: | (1) IGEA SpA, Clinical Biophysics, Via Parmenide 10/A, 41012 Carpi, MO, Italy;(2) Laboratory of Preclinical and Surgical Studies, Research Institute Codivilla-Putti, Rizzoli Orthopaedic Institute, Bologna, Italy; |
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Abstract: | Articular cartilage is a complex tissue characterised by chondrocytes that are embedded within an organised dense extracellular
matrix of collagen and proteoglycan. Under physiologic condition, articular metabolism is slow, but under pathological condition
turnover can increase and the matrix undergoes faster mechanical failure and deterioration, resulting in cartilage degeneration.
Moreover, modest damage of the articular cartilage, resulting from trauma or less invasive surgical procedure, produces an
inflammatory reaction of the joint cartilage, which can cause irreversible degeneration through the increase in catabolic
cytokines synthesis and the decrease in anabolic activity of chondrocytes. Pro-inflammatory cytokines increase the synthesis
of matrix-degrading enzymes and limit the production of proteoglycans. It is known that physical stimuli modulate cartilage
metabolism. In particular, pulsed electromagnetic fields (I-ONE therapy, Igea, Carpi, Italy) allow to treat homogenously the
whole cartilage surface and thickness and the underlying subchondral bone. In vitro I-ONE therapy increases the binding between
adenosine and A2A adenosine receptor on human neutrophils cell membrane, on bovine chondrocytes and on fibroblast-like synoviocytes. It has
been shown that drugs with A2A adenosine receptor agonist activity prevent articular cartilage degeneration in animals. We hypothesised that the adenosine
agonist effect of I-ONE therapy can also prevent cartilage degeneration. In a recent study, De Mattei et al. demonstrated
how I-ONE therapy can strongly inhibit the release of PGE2 in bovine synovial fibroblasts exerting an anti-apoptotic effect on cells. Ex vitro, in bovine full thickness articular cartilage explants, I-ONE therapy induces the largest increase in proteoglycan synthesis
and in IGF-1 synthesis, when cartilage is exposed to specific parameters of pulsed electromagnetic fields. These effective
parameters were subsequently used in in vivo experiments. The effect of I-ONE therapy was investigated on Dunkin Hartley osteoarthritic
knee by Mankin score and by histomorphometric and densitometric analysis; I-ONE therapy prevented cartilage degeneration and
subchondral bone sclerosis. Osteochondral grafts were performed in the knees of sheep; I-ONE therapy favoured osteochondral
grafts integration and prevented cyst-like resorption area formation, which can compromise the stability of graft and the
success of the technique. To support the in vitro results, biochemical analyses of the synovial fluid were also performed
in this animal model. The amount of inflammatory catabolic cytokines (IL-1β and TNF-α) in the synovial fluid of I-ONE treated
animals was significantly lower than in control animals. On the contrary, TGF-β1 was significantly higher in stimulated animals
than it was in controls. These results demonstrate not only the capability of I-ONE therapy to control the inflammatory reaction
but also its capability to favour cartilage anabolic activity. These results provide the rational to design clinical studies
to demonstrate the possibility to transfer the treatment to humans. Two randomised, prospective, double-blind clinical studies
(Level I), one conducted to patients treated by arthroscopy with condroabrasion and/or perforations at the knee and the other
after anterior cruciate ligament reconstruction, demonstrated that biophysical stimulation with I-ONE therapy leads to complete
patient’s recovery in a significantly shorter time (P < 0.005). Moreover, a significant number of treated patients made lower use of anti-inflammatory drugs than the patients
in the placebo group. We did not observe negative side effects, patient’s compliance was good and treatment was well accepted.
I-ONE therapy significantly reduces patients’ recovery time, joint swelling and has a chondroprotective effect over articular
cartilage. I-ONE treatment is a new therapy for the joint preservation. |
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