## 4 Future Perspectives  
Future clinical indications are still at the stage of in vitro studies in particular regarding the dynamic behavior of cellular structures. However, current evidence seems to suggest that these treatment approaches will become increasingly widespread in the clinical setting. These evolutions do not concern only BME, OCD, fractures, and nonunions, but many other conditions, such as tendons painful conditions. PEMFs treatment on BME is known to promote osteogenic activity, and to prevent subchondral bone collapse. This treatment appears the more effective the earlier BME is diagnosed [7; 13]. Future perspectives should focus not only on the BME cellular mechanisms in response to PEMFs, but also on exploring new clinical and imaging tools to make early diagnosis. PEMFs seems to play a role in helping stem cells to differentiate into mature hyaline cartilage cells, in particular by decreasing pro-inflammatory cytokines releases [29; 31]. These properties have been reported in vitro with bone marrow-derived mesenchymal stem cells [29; 31], but in the future should be evaluated also in vivo, comparing different sources of stem cells: bone marrow, adipose tissue, synovial membrane, etc. The role of PEMFs is well established in the treatment of fractures, and nonunion. However, future perspectives should focus on histological analysis to better to understand how the bone healing process works, both in physiological and pathological settings. Randomized controlled trials would be a worthwhile endeavor. Tendons, as well as fasciae [52], may benefit from PEMFs therapy. Tendons painful conditions in response to overuse are known as tendinopathies: in addition to degenerative aspects, inflammatory mediators have been found to be sometimes present [57; 58]. [PERSON] et al. [58] studied the interaction between inflammation and matrix remodeling in human tendon cells (TCs) and demonstrated that the attempt of TCs to counteract the catabolic/inflammatory state induced by IL-1\(\beta\) is in part mediated by A2A, Rs and reinforced by PEMF treatment [58]. These findings demonstrated that A2A, Rs have a role in the promotion of the TC anabolic/reparative response to PEMFs and to IL-1\(\beta\). [PERSON] et al. [59; 60] studied the effect of PEMF treatment (1.5 mT, 75 Hz) on chronic tendinopathy, a degenerative process causing pain and disability [59; 60]. PEMF'seffect was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of patients, under different experimental conditions. Authors found that PEMF, in a dose-dependent manner, enhance the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model. In tendon regeneration, the use of PEMFs together with mesenchymal stem cells (MSCs) is another intriguing option, but still investigational. [PERSON] et al. [61] investigated the effect of PEMF on MSCs isolated from the human umbilical cord (UC-MSCs) and found that PEMF exposure generates a biophysical preconditioning effect on UC-MSCs, promoting the expression of tenogenic markers and anabolic cytokines involved in tendon regeneration [61]. These results have a clinical relevance, suggesting a possible large-scale clinical application of this approach as an adjuvant non-invasive therapy in the early postoperative period of tendon surgical repair. In addition, a study conducted on culture of tendon derived cells from healthy donors, who underwent knee anterior cruciate ligament reconstruction with autologous hamstring, showed that PEMFs may represent a possible tool for enhancing and accelerating the physiological ligamentization process during the postoperative period of tendon reconstruction [62]. The role of PEMF in improving the tendon healing process was also evaluated in a rat model of collagenase-induced Achilles tendonopathy [63; 64].