**2. Muscle healing**

Muscle injuries are debilitating injuries, especially for athletes who risk setbacks in their career. A subcutaneous muscle tear can be caused by direct trauma, such as a contusion from a blunt object or strains, or by indirect trauma such as ischemia or a neurological dysfunction [2]. In any case these injuries are difficult to treat and unfortunately there are no clear and defined guidelines to help the physician [3].

From a biological point of view muscles have been shown to be particularly active and capable of excellent tissue regeneration. The gap between the muscle fibers is filled thanks to the myocyte cell reactivity, the presence of replicative phase cells and the production of connective tissue scar.

The healing process of muscle injury consists of three phases: the degeneration-inflammation phase, the reparative phase and the remodeling-fibrosis phase (Figure 1).

The first phase (first few days post-injury) is characterized by inflammatory stimulation caused by the cellular debris and the pro-inflammatory molecules that are released as a result of necrosis of the injured tissue; also the severed blood vessels release blood within the tissue forming hematoma, which in turn stimulates the inflammatory response. This cascade of events results in the release of cytokines, interleukins, adhesion molecules (e.g., P-selectin, Lselectin, E-selectin), Tumor Necrosis Factor alpha and growth factors (e.g. insulin-like growth factor 1 IGF-1, hepatocyte growth factor HGF, EGF, epidermal growth factor, transforming growth factor alpha and TGF beta, platelet-derived growth factor PDGF) that promote inflammation, cell migration and stimulate progress to the next stage [2 - 3]

The reparation phase (from day 7-10 to week three-four post-injury) begins with the cleaning of the tissue formed in the acute phase by macrophages that engulf the injured tissue and allow the regeneration of tissue within the lesion: it stimulates the proliferation of striated muscle tissue, the neo-angiogenesis within the neo-tissue and stimulates the production of connective scar tissue. The cells that are more active from the point of view of replication (myogenic precursor cells, or satellite cells) are located between the basal lamina and the plasma mem‐ branes of each individual myofiber; once they are released by the lesion of the basal lamina and activated by growth factors, they differentiate into myoblast and replicate forming multinucleated myotubes and possibly myofibers.

The final phase, the remodeling-fibrosis, involves the maturation of the neo-muscle tissue and the reorganization of the scar tissue, and is strongly driven by mechanical stress and the stress of the surrounding tissue that drive the neo-tissue to organize in the most functional way possible for contraction. The connective tissue produced is partly demolished, gradually leaving more space for the connections between the myofibers [4].

Some authors tend to wide the indication for surgical treatment to lesions greater than 50% of the thickness of the muscle belly and the debate is still open because of the few tests to date available, but certainly the indication is strengthened by the absence of synergistic muscles

The aim of this chapter is to perform a review of the literature in order to identify the muscle

Muscle injuries are debilitating injuries, especially for athletes who risk setbacks in their career. A subcutaneous muscle tear can be caused by direct trauma, such as a contusion from a blunt object or strains, or by indirect trauma such as ischemia or a neurological dysfunction [2]. In any case these injuries are difficult to treat and unfortunately there are no clear and defined

From a biological point of view muscles have been shown to be particularly active and capable of excellent tissue regeneration. The gap between the muscle fibers is filled thanks to the myocyte cell reactivity, the presence of replicative phase cells and the production of connective

The healing process of muscle injury consists of three phases: the degeneration-inflammation

The first phase (first few days post-injury) is characterized by inflammatory stimulation caused by the cellular debris and the pro-inflammatory molecules that are released as a result of necrosis of the injured tissue; also the severed blood vessels release blood within the tissue forming hematoma, which in turn stimulates the inflammatory response. This cascade of events results in the release of cytokines, interleukins, adhesion molecules (e.g., P-selectin, Lselectin, E-selectin), Tumor Necrosis Factor alpha and growth factors (e.g. insulin-like growth factor 1 IGF-1, hepatocyte growth factor HGF, EGF, epidermal growth factor, transforming growth factor alpha and TGF beta, platelet-derived growth factor PDGF) that promote

The reparation phase (from day 7-10 to week three-four post-injury) begins with the cleaning of the tissue formed in the acute phase by macrophages that engulf the injured tissue and allow the regeneration of tissue within the lesion: it stimulates the proliferation of striated muscle tissue, the neo-angiogenesis within the neo-tissue and stimulates the production of connective scar tissue. The cells that are more active from the point of view of replication (myogenic precursor cells, or satellite cells) are located between the basal lamina and the plasma mem‐ branes of each individual myofiber; once they are released by the lesion of the basal lamina and activated by growth factors, they differentiate into myoblast and replicate forming

The final phase, the remodeling-fibrosis, involves the maturation of the neo-muscle tissue and the reorganization of the scar tissue, and is strongly driven by mechanical stress and the stress

phase, the reparative phase and the remodeling-fibrosis phase (Figure 1).

inflammation, cell migration and stimulate progress to the next stage [2 - 3]

multinucleated myotubes and possibly myofibers.

that can decrease the workload to the muscle and therefore aid healing.

injury which indicate surgical treatment and its results.

**2. Muscle healing**

222 Muscle Injuries in Sport Medicine

tissue scar.

guidelines to help the physician [3].

**Figure 1.** The diagram summarizes the three phases of muscle laceration healing. Note that reparation has a peak around the second week and concludes by the third- fourth week [2].

Fibroblasts that colonize the lesion and produce extracellular matrix play a key role in lesion healing. The connective tissue that is formed fills the gap created by the lesion with a threedimensional plot that not only guides the proliferation of muscle cells and blood, but allows the transmission and the distribution of mechanical stresses thus acting as a sort of brace and allowing the functional use of the muscle before the lesion is completely healed. It was observed that animal muscles, thanks to this connective tissue, already after 14 days the scar that had formed in complete tears was mechanically more resistant than the surround‐ ing muscle [4]. It should be kept in mind that in human tissue healing times are longer and recovery is less complete but the sequence and function of the repair steps are the same [5].

This scar tissue is extremely important but it can also be an obstacle to proper healing: in fact, if there is too much of it, instead of promoting, it may prevent tissue proliferation leading to incomplete recovery [3]. A proper healing of muscle tissue is centered on the correct balance between fibroblastic proliferation and myoblast proliferation: the first promote the connective tissue that must act as a scaffold for the repopulation of the lesion by the myoblasts. When the lesion is too large, however, the gap between the proximal and the distal stump is filled with granulation tissue which results in connective tissue scar [6, 7] leaving little room for myoblast proliferation. It is possible that in the final phase (remodeling) structural improvements of the scar may occur but they are only minor [5].

The healing of the lesion depends not only on cell reactivity and the amount of scar tissue, but is closely linked to many other factors. The innervation of the tissue remaining promotes tissue viability: an excessive presence of denervated myocytes downstream of the lesion impairs proper healing [1]. Other aspects to be considered are the supply of oxygen from the sur‐ rounding tissue, the vascular proliferation and neo-angiogenesis within the lesion in the posttrauma stage, the percentage and the pattern with which the myoblasts go to form the myotubes and the collagen crosslinking [8].
