Three Phases of Muscle Injury and Healing

DESTRUCTION PHASE:

Initial rupture and necrosis of myofibers

• However, within hours the propagation of necrosis is halted to a local process (similar to a "fire door" mechanism)

Hematoma formation occurs between the ruptured stumps of the myofibers

Blood vessels tear and release inflammatory cells

• Later, inflammation is amplified as “wound hormones” are released by satellite cells and necrotized myofibers – these act as chemotactants, signaling for further inflammation

*Note: Repair and Remodeling Phases Are Concomitant – simultaneously supportive and competitive


REPAIR PHASE:

Phagocytosis of necrotized tissue

• Initially, polymorphonuclear leukocytes are the most abundant cells but within the first day, these are replaced by monocytes/macrophages which proteolyse and phagocytose the necrotic tissue

Regeneration of myofibers

• Pool of satellite cells beneath the basal lamina (present since fetal development) proliferate in response to injury, differentiate into myoblasts, and join together to form multinucleated myotubes (these myotubes then fuse with the injured myofiber that survived the trauma)
• Undifferentiated stem cells which are extralaminally within the connective tissue give rise to determined myoblasts and differentiate to myotubes
• Regeneration of intramuscular nerves is also necessary as a lack of reinnervation of the myofiber results in atrophy

Production of a connective tissue scar

• Initial injury results in a hematoma but within the first day, the hematoma is invaded by inflammatory cells (including phagocytes)
• Blood-derived fibrin and fibronectin cross-link to form a scaffold and anchorage site for the invading fibroblasts
• Fibroblasts then start synthesizing the proteins and proteoglycans of the ECM to restore the integrity of the connective tissue framework
• Fibronectin is followed by Type III collagen. (Type I collagen production is initiated days later).
• The initially large granulation tissue (scar) eventually condenses into a small mass made up mostly of Type I
• The scar is initially the weakest point but infusion of TYPE I collagen (and the cross-link formation with maturation) makes it stronger (tensile strength) than the adjacent myofibers by day 10 post-injury. Therefore, reinjury ISN'T simply the "breaking up of scar tissue"

Capillary in-growth into injured area

• Vascularization is the first sign of regeneration and required for subsequent recovery process
• New capillaries have only a moderate capacity for aerobic metabolism and, therefore, rely on anaerobic means
• BUT during the final stages of regeneration, aerobic metabolism is needed (principle energy pathway) for the regeneration of myofibers - Regeneration does not progress beyond the newly formed thin myotube stage unless a sufficient capillary in-growth has ensured the required supply of oxygen for the aerobic metabolism 

REMODELING PHASE:

Maturation of the regenerated myofibers

Contraction and reorganization of the scar tissue 

• Myofibers that survived form branches as well as try to pierce through the scar on either side. The branches adhere to the connective tissue (scar) to form mini-Muscle Tendon Junctions. As mentioned above, the scar, therefore becomes stronger than its adjacent myofibers, rendering the myofibers more susceptible to injury if reaggravated
• Reinforced lateral adhesions (branches) also form to reduce the movement of the stumps and reduce the pull on the fragile scar. These lateral adhesions are formed as a result of intentional mechanical stress (free/forced mobilizations)
• Overtime the scar progressively diminishes bringing the stumps closer together – until the myofibers become interlaced (though likely not reunited)

Recovery of the functional capacity of the muscle

• Depends on severity of injury and nature of hematoma (intra vs inter muscular hematoma) of the injured muscle

*The above review was a brief summary of Jarvinen's review on Muscle Injuries in the Americal Journal of Sports Medicine