Abstract

Skeletal muscle tissue has inherent capacity for regeneration in response to minor injuries. However, in the case of severe trauma, tumor ablations, or in congenital muscle defects, these myopathies can cause irreversible loss of muscle mass and function, a condition referred to as volumetric muscle loss (VML). The natural muscle repair mechanisms are overwhelmed, prompting the search for new muscle regenerative strategies, such as using biomaterials that can provide regenerative signals to either transplanted or host muscle cells. Recent studies involve the use of suitable biomaterials which may be utilized as a template to guide tissue reorganization and ultimately provide optimum micro-environmental conditions to cells. These strategies range from approaches that utilize biomaterials alone to those that combine materials with exogenous growth factors, and ex vivo cultured cells. A number of scaffold materials have been used in the development of grafts to treat VML. In this brief review, we outline the natural skeletal regeneration process, available treatments used in the clinic for muscle injury and promising tissue bioengineering and regenerative approaches for muscle loss treatment.

Highlights

  • Skeletal muscle tissue has inherent capacity for regeneration in response to minor injuries

  • Under circumstances of severe injuries – muscle mass loss greater than 20%1 – tissue repair response is incapable of adequate tissue regeneration, and may lead to extensive and irreversible fibrosis, scarring, and loss of muscle function[4]

  • Major trauma with lasting functional impairment sustained from motor vehicle accidents, combat- or sport-related injuries, aggressive tumor ablation, prolonged denervation and other causes is defined as volumetric muscle loss (VML)[4,5,6,7]

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Summary

Conclusion

Skeletal muscle regeneration is a complex and highly regulated process involving the activation and interplay of various processes, such as the inflammatory response, growth factor and survival signaling, stem cells-mediated repair regeneration of muscle cells and fibroblast infiltration with or without scar tissue formation[2]. The major limitations in VML injury repair of the affected muscle are the complete destruction/removal of the basal lamina and the loss of other structural muscle constituents, such as the damage to the stem cell niche (e.g. satellite cells)[2]. Fibroblasts will infiltrate the injury site (as early as the inflammatory phase) and help regeneration by providing support and replacing the damaged connective tissue[13].

Current Treatments
Challenges and limitations
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