The repair capacity spectrum of human skeletal muscle injury from sports to surgical trauma settings.

Skeletal muscle injury and repair have been a major research focus for more than a century. Muscle injuries are defined by their cause and anatomical location and lie on a spectrum in terms of repair outcomes. From contraction-induced necrosis, which initiates regenerative myogenesis for complete restoration of tissue architecture and function to, at the other end of the spectrum, traumatic volumetric muscle loss (VML), where substantial portions (or the whole) of a muscle are lost, leaving the patient with permanent physical disability. Strain injuries are found between these two extremes and are characterised by healing with scar tissue formation and a high re-rupture rate. Across these injury types, a discriminating feature for a successful outcome is the preservation of the extracellular matrix (ECM) architecture of the muscle-tendon complex, in particular the myotendinous junction (MTJ). Numerous experimental models, imaging techniques and molecular analyses have led to a thorough understanding of how muscle stem cells interact with immune, vessel and stroma-associated cells during regenerative myogenesis. Paradoxically, treatment of muscle strain injury and VML has not improved, and regenerative engineering approaches remain a distant hope. Important issues for this field include matching the level of detail that exists for animal muscle regeneration with human data and identifying the site of tissue disruption during strain injury. We propose that a closer collaboration between cell biologists, physiologists, sports medicine practitioners and orthopaedic surgeons is required to improve patient outcomes, particularly for strain injuries and VML.