Regeneration of injured skeletal muscle after the injury

Abstract

Muscle injuries are one of the most common traumas occurring in sports. Despite their clinical importance, few clinical studies exist on the treatment of these traumas. Thus, the current treatment recommendations for muscle injuries have either been derived from experimental studies or been tested only empirically. Although non operative treatment should almost always be the 1(st) choice as it results in good functional outcomes in the majority of athletes with muscle injuries, the consequences of failed treatment can be very dramatic, possibly postponing an athlete's return to sports for weeks or even months. Moreover, the recognition of some basic principles of skeletal muscle regeneration and healing processes can considerably help in both avoiding the imminent dangers and accelerating the return to competition. Accordingly, in this review, the authors have summarized the prevailing understanding on the biology of muscle regeneration in hopes of extending these findings to clinical practice in an attempt to propose an evidence-based approach for the diagnosis and optimal treatment of skeletal muscle injuries.

Keywords: NSAID; contusion; eccentric exercise; immobilization; skeletal muscle; strain.

Figures

Figure 1.

The regeneration of a shearing injury. (A) Torn myofiber and BL. (B) Contraction band and demarcation membrane seal the torn fiber ends. Satellite cells (SC) begin to proliferate and inflammation reaction begins. (C) SCs differentiate into myoblasts and fibroblasts begin to produce collagens and form scar tissue. (D) Myoblasts fuse into myotubes. (E) Myotubes fuse with the surviving parts of the torn fibers and start to form new MTJs. (F) Fully regenerated fiber with organized scar tissue and MTJs attached to it.

Figure 2.

A schematic presentation of fetal development (A1-B1-C-D) and regeneration of myofibers via the activation of satellite cells (A2-B2-C-D or A3-B3-C-D). Satellite cells have been set aside underneath the basal lamina during the fetal development (A2 and A3) to be used in growth and repair. After injury, the committed satellite cells (csc) immediately begin differentiation into myoblasts (mb) without prior cell division (B2), while the stem satellite cells (ssc) first divide, and only then one of the daughter cells differentiates into a myoblast (B3), whereas the other replenishes the pool of stem satellite cells (B4). Myoblasts fuse into myotubes (mt), which then grow and mature into myofibers, the sarcoplasm of which becomes filled with contractile filamentous proteins organized as myofibrils and with the myonuclei located subsarcolemmally. mpc, myogenic precursor cell.

Figure 3.

A) In strains not only the myofibers rupture but also their basal lamina as well as mysial sheaths and blood vessels running in the endo- or perimysium are torn. The ruptured myofibers become necrotized only over a short distance. B) The injured part of the ruptured myofiber inside the remaining old basal lamina is replaced by the regenerating myofiber, which then begins to penetrate into the connective tissue scar between the stumps of the ruptured myofibers. C) The maturation of the regenerating myofibers includes formation of a mature contractile apparatus and attachment of the ends of the regenerated myofibers to the intervening scar by newly formed MTJs. The retraction of the scar pulls the ends closer to each other, but they appear to stay separated by a thin layer of connective tissue to which the ends remain attached by newly formed MTJs.

Figure 4.

Comparison of skeletal muscle healing by immobilization vs active, early mobilization. The injured muscle were immobilization by cast for two after which the cast were removed in the mobilization group (MO) and the exercise protocol was started. The cast immobilization continued in the IMMO-group until day 21. As can be seen, the injured skeletal muscle regains the strength fast when the active early mobilization is started, whereas no regeneration takes place if the inactivity (immobilization) persists highlighting the importance of the active rehabilitation of the injured skeletal muscle.