**27. The adherence of the myofiber to the ECM**

At the moment in which a myofiber loses its continuity also the continuity of the unit "tendonmuscle-tendon" is interrupted at the point of breakage itself and the contractile force cannot be transmitted through the gap which has been created between the stumps of the fibers. In such a situation, in fact, during muscular contraction the stumps are simply pushed further

**25. The re-vascularization of the injured muscle**

38 Muscle Injuries in Sport Medicine

restoration of the aerobic mechanism.

restabilized.

**26. The regeneration of intramuscular nerves**

**27. The adherence of the myofiber to the ECM**

A fundamental process in the field of reparation of the injured muscle, is represented by the re- vascularization of the injured area (Snow, 1973; Järvinen, 1976; Józsa et al., 1980;). The restoration of vascularization in the injured area, represents the first sign of reparation and it is a pre-requisite for the successive morphological and functional recuperation of the injured muscle. The new capillary network has origin of the survived trunks of the blood vessels which go towards the centre of the trauma area (Järvinen, 1976) and they go to supply the same area with an adequate amount of oxygen allowing, in such a way, the successive functional restoration of the aerobic metabolism, which represents, in its turn, a fundamental stage in the field of repair process of the myofibers. The young myotubes are supplied with few mito‐ chondria and only show a moderate functional capacity in the field of the energetic aerobic restoration mechanism but they contextually present a clear increase in the energetic anaerobic restoration mechanism (Järvinen and Sorvari, 1978). In any case, during the final phases of tissue repair, the aerobic metabolism makes up the principle energetic resource for the multinuclear myofibers (Järvinen and Sorvari, 1978). This particular repair procedure, also supplies a plausible explanation of why the regeneration of the myofibres doesn't progress further than the precocious formation phase of slim myotubes, up until when the growth of a sufficient capillary network can't assure the necessary oxygen contribution to a satisfying functional

Similarly to what happens in the course of the process of re-vascularization, the healing of the skeletal muscle may be blocked by a failure in the regeneration of intramuscular nerves (Hurme et al., 1991; Rantenen et al., 1995; Vaittinen et al., 1999; Vaittinen et al., 2001). The regeneration of the myofiber continues from the phase of myotubes formation also in absence of innervations; but if innervations were not completed correctly, a process of atrophy would inevitably occur (Rantanen et al., 1995). In the case of neurogenic denervation, or the breakage of the axon, the re-innervation process requires the growth of a new axon, distally with respect to the breakage area. However, since the moment the axons usually undergo go thorug a breakage inside or around the muscle, the nerve-muscle contact is, generally, rapidly raidly

At the moment in which a myofiber loses its continuity also the continuity of the unit "tendonmuscle-tendon" is interrupted at the point of breakage itself and the contractile force cannot be transmitted through the gap which has been created between the stumps of the fibers. In such a situation, in fact, during muscular contraction the stumps are simply pushed further

**Figure 8.** Schematic representation of a breakage trauma of the skeletal muscle. The injured muscle fiber contract and the gap between the stumps, or the central zone CZ; initially begins to fill with the hematoma. The muscular fibers are necrotic inside their basal lamina, of a distance which is usually between 1 and 2 millimeters. Inside this segment gen‐ erally, with time, complete repair occurs (repair zone RZ; we prefer, in this case, the term "repair zone" to the term "regeneration zone" used by anglo-saxon autors. The reason of this choice derives from the different biological con‐ cept between the term "repair" and "regeneration", already illustrated at the beginning of the chapter), whereas in the part of the muscle which is not injured by trauma, we may observe only changes of reactive type (survival zone SZ). Each muscular fiber is innerved, in a single and precise site,by a neuromuscular junction (NMJs, full point in the dia‐ gram). Since the muscular fibbers generally break from one or the other side with respect to the line of NMJs of the same fiber, the accessory stumps of fibre 1 and of the fibres that go from 3 to 5, of the "ad" side (right), remain in‐ nerved, whereas their accessory stumps on side"ab" (left), remain denerved. At the same time the accessory stump of fibre 2 has remained denerved, because its NMJ is found in the RZ zone. The re-innervation of the accessory stump will come about through the penetration of a new axon sprout through the scar zone in formation (CZ) and so thanks to the formation of a new NMJ (represented by the white point in the diagram ). Fibre 2 will go back to its normal reinnervation when the repair process in zone RZ is completed.

aside. The final part of the myofibers in repair which attempt to pass through the scar tissue, maintains a visible growth cone for a relatively long period during the repair process (Hurme et al., 1991; Hurme and Kalimo, 1992), this represents a period of time during which the final part of the myofibers cannot adhere firmly to the scar tissue. However, the myofibers in the course of repair strengthen their adherence to the ECM in both parts of their lateral profile, both in their intact part and in the part of re-growth (Kääriänen et al., 2000; Sorokin et al., 2000; Allikian et al., 2004) (Figure 9), This strengthening of the lateral adherence reduces both the movement of the stumps and the push on the still fragile scar, reducing in such a way the risk of re-breakage and allowing, at the same time, some use of the injured muscle before the healing process is complete (Kääriänen et al., 2001; 2002). It appears very interesting the fact of how mechanical stress is a pre-requisite for the process of lateral adherence, as recently some studies have suggested that they show how the phenomena does not come about in absence of the latter (Kääriänen et al., 2001). In a more advanced phase of the repair process a strong terminal adherence at the end of each stump is stabilized, which consists in the same type of molecule associated with integrin and distrofin that we can observe in a normal MJT (Song et al.., 1992; Kääriänen et al., 2000a; 2000b; 2001; 2002) (Figure9). Contextually, the original (prelesion) unit "tendon-myofiber-tendon, is replaced by two consecutive units of "tendonmyofiber-mini MTJ " type separated by the scar. These two consecutive units contract at the same time, thanks to the fact that both are re-innerved by the same nerve (Rantanen et al., 1995). In the ECM, on a level of the place of the new MTJs, elastic and adhesive molecules are profusely expressed, whose role is to absorb the strength created by the muscular contractions (Hurmea and Kalimo, 1992; Järvinen et al., 2000). At this point of the repair process, having re-established solid terminal adhesions through these mini MTJs, the myofibers no longer need lateral adhesions of strengthening and, consequently, the strong expression of integrin decreases on a level of the lateral sarcolemma (Kääriänen et al., 2000a). The scar gradually diminishes in dimension, in such a way the stumps come close to each other and in the end the myofibers become intertwined, even though, not fully reunited (Kääriänen et al., 1998; 2000a; Vaittinen et al., 2002) (figure9 box C).

**28. Conclusions**

**Author details**

Gian Nicola Bisciotti1

**References**

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approach to the treatment of muscle injuries.

and Cristiano Eirale1,2

2 Kinemove Rehabilitation Centers, Pontremoli, Parma, La Spezia, Italy

Proceedings of the Royal Society B 139: 104-117, 1951

Today there are only a few clinical studies concerning the treatment of muscular lesions, for this reason the principles of current treatments are mainly based on experimental studies or only on empirical evidence. The experimental studies have shown that the biological basis of the processes that occur during muscle repair are identical regardless of the primary cause of the injury (contusion, elongation or tear). This emphasizes the importance of understanding the basic principles of muscle repair, which represent the essential pre-requisite for a correct

Etiology, Biology and Treatment of Muscular Lesions

http://dx.doi.org/10.5772/56602

41

1 Qatar Orthopaedic and Sport Medicine Hospital, FIFA Center of Excellence, Doha, Qatar

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**Figure 9.** At the beginning of the healing process of the injured skeletal muscle (Box A ) the expression of cellular adhesion of the integrin α7β1 molecules is enriched in the terminal part of the fibers of the damaged muscle in regen‐ eration phase, whereas only a small amount of the latter are present in the lateral profile of the myofiber. A dramatic increase in the expression of integrin α7β1 happens along the lateral aspect of the plasmatic membrane (Box B ), both in the intact part and in the part in growth phase of the injured myofibers, at the moment in which the muscular fibers in repair phase penetrate the injured tissue. In such a way, the integrin α7β1 supplies stability to the muscular fibers in growth phase which are missing in adhesion in their terminal part. The expression of the integrin α7β1 returns to nor‐ mal levels in the lateral sarcolemma (Box C) contextually to the normality of the re-distribution of the integrin α7β1 in the terminal part of the fibers in repair, when the latter form new myotendon junctions and adhere to the scar.
