## 4 Discussion  
This is the first study to report a case of conservative treatment of non-surgical MCL injury with US-guided f-ESWT. The spontaneous healing of tendons and ligaments is slow and often incomplete [14,15]. Moreover, prolonged immobilization should be avoided, since it has been demonstrated to enhance collagen degradation and bone resorption at the ligament insertion point [16]. However, due to the extra-articular location, MCL has a high healing potential compared with intra-articular ligaments (such as anterior cruciate ligament of the knee); therefore, most of the injuries can be treated conservatively and they rarely require a surgical intervention [8]. Despite this, due to the histological and volumetric characteristics of the mass of healing tissue, the chemical and biomechanical properties of the injuries MCL often fail to return to normal [17]. Among conservative therapies for the management of tendon injuries, ESWTs (and in particular f-ESWT) have gained increasing interest in recent years due to the induced biological responses, including tissue regeneration, wound healing, angiogenesis, and bone remodelling. Additionally, f-ESWT may also alleviate pain by stimulating analgesia [9]. However, to the best of our knowledge, few articles have described the effects of f-ESWT on ligament injury of in vitro and in vivo models, and no scientific works have been published regarding the usefulness of f-ESWT in the treatment of ligament injuries in humans [18,19]. Figure 2: The 4-month follow-up ultrasound (US) examination of the MCL at the site of the previous injury (arrow). Tendons and ligaments are types of fibrous connective tissue that connect muscle to bone and bone to bone, respectively. They represent crucial structures for the transmission of forces and the stabilization of the musculoskeletal system. Structurally and physiologically, tendons and ligaments are very similar. Additionally, the delineation between the two is not always clear and many of their characteristics overlap and differ at the same time (ECM composition, collagen I/collagen III and collagen/elastin ratio composition, orientation of collagen fibers) [20; 21; 22]. For this reason, it seems plausible to use the same type of physical energy as a form of conservative treatment even in the case of ligamentous injuries. Previous studies have demonstrated the potential of ESWT in promoting bone healing and increasing the realignment of tendon and ligament fibers in vivo [23]. The hypothesis of f-ESWT leading to tissue regeneration is based on the mechanotransduction model: a mechanical stimulus applied to the cytoskeleton stimulates protein biosynthesis and proliferation. In vitro studies showed a protective role in leucytes and an increased synthesis of type I collagen. Moreover, a significant increase in glycosaminoglycans (GAGs) and protein synthesis in tendons was observed [12]. These actions seems to be related to specific cellular signaling pathway activation, thus leading to increase in ATP release and activation, enhancing cell proliferation, differentiation, and regeneration [24; 25]. [PERSON] et al. evaluated the effects of ESWT on extra-cellular matrix components of affected ligaments in the hind limbs of horses, using ultrasonographic, ultrastructural, and immunocytochemical techniques [13]. Four weeks after treatment, ESWT-treated tissue demonstrated smaller, newly formed collagen fibrils and a greater expression of transforming growth factor beta (TGF-\(\beta\)), indicating that ESWT appears to facilitate the healing process. Moreover, a TGF-\(\beta\)1 inhibitor activity on macrophage-mediated ECM degradation during wound healing has been demonstrated [26]. Another study reported that low-energy f-ESWT can lead to M2 macrophage phenotype differentiation, which is typically characterized by anti-inflammatory properties. Indeed, M2 macrophage activity induces IL-4, IL-5, IL-9, and IL-13 biosynthesis, as well as collagen synthesis, angiogenesis, and tissue remodeling [27].