Regenerative medicine for skeletal muscle loss: a review of current tissue engineering approaches

Skeletal muscle is capable of regeneration following minor damage, more significant volumetric muscle loss (VML) however results in permanent functional impairment. Current multimodal treatment methodologies yield variable functional recovery, with reconstructive surgical approaches restricted by limited donor tissue and significant donor morbidity. Tissue-engineered skeletal muscle constructs promise the potential to revolutionise the treatment of VML through the regeneration of functional skeletal muscle. Herein, we review the current status of tissue engineering approaches to VML; firstly the design of biocompatible tissue scaffolds, including recent developments with electroconductive materials. Secondly, we review the progenitor cell populations used to seed scaffolds and their relative merits. Thirdly we review in vitro methods of scaffold functional maturation including the use of three-dimensional bioprinting and bioreactors. Finally, we discuss the technical, regulatory and ethical barriers to clinical translation of this technology. Despite significant advances in areas, such as electroactive scaffolds and three-dimensional bioprinting, along with several promising in vivo studies, there remain multiple technical hurdles before translation into clinically impactful therapies can be achieved. Novel strategies for graft vascularisation, and in vitro functional maturation will be of particular importance in order to develop tissue-engineered constructs capable of significant clinical impact.