In vivo evaluation of decellularized skeletal muscle matrices for skeletal muscle repair: A systematic review

Volumetric muscle loss is the significant loss of skeletal muscle volume beyond the innate regenerative capacity, resulting in functional impairment. The current standard of care combines muscle autografting with physical therapy but is often insufficient to reach full recovery. Decellularized skeletal muscle (DSM) provides an interesting alternative to repair volumetric muscle loss. The native structure and composition of the extracellular matrix in these acellular implants provide a blueprint for muscle regeneration. Moreover, DSM can be combined with cells to facilitate the regeneration of the skeletal muscle defect. This systematic review provides a complete and thorough overview of the state-of-the-art applications and efficacy of DSM matrices in skeletal muscle repair in vivo, selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Technical information on the different methods to create DSM implants and the implantation studies is provided. Moreover, details on the evaluation of the structural and functional regeneration of the muscle defect after implantation of the DSM are described. Results reveal a large heterogeneity in the analysis of regeneration upon DSM implantation. This heterogeneity makes it difficult to fully assess the efficiency of DSM to regenerate skeletal muscle, hampering further translation of this technique. Therefore, we suggest a multi-level evaluation method to assess (i) muscle regeneration, (ii) vascularization, (iii) innervation of the regenerated muscle, and (iv) functional regeneration in a quantitative way.