Soft tissue injuries, especially skeletal muscle ones, are very common in daily life. Besides military personnel exposed to a wide series of combat-related trauma 
, civilian categories such as athletes, construction workers, or simply people behind the wheel are frequently victims of these kinds of incidents 
. Unfortunately, VML occurs in a large percentage of muscle-related trauma, often leading to the development of chronic disability 
. Actual therapies consist in wound debridement and surgical reconstruction by using free muscle flaps and physical training 
. However, in the majority of the cases, these approaches are unsatisfactory, and the recovery of both aesthetically and functionality is completely inadequate 
. For these reasons, there is a need for reconstructive therapies based on skeletal muscle tissue engineering. Whereas preclinical studies on animal models are very promising, especially those conducted on rodents (Costantini et al., 2021 doi: 10.15252/emmm.202012778),
actual clinical treatments based on acellularized scaffolding are not enough to achieve a promising therapeutic approach 
. Thus, the real challenge today is still the jump up from these cells-based therapeutic strategies to human size. At the present time, studies on large animal models are few, and the preliminary outcomes are not at all encouraging 
. In addition, although the literature is exhaustive on the issues related to VML in terms of incidence 
, implication, current therapies, and emerging reconstructive strategies, some aspects need to be further investigated at a scientific level, such as consequences of volumetric loss on the prosthesis socket, the reduction of the contact surface on a prosthesis, and effects of re-innervation tagging on a reconstructed mass (Figure 1
). We are confident that skeletal muscle tissue engineering is the right way to resolve the highly disabling pathology that negatively affects the quality of life of people suffering from VML-related pathologies. Furthermore, this reconstructive approach would be notably useful for replenishing prosthesis sockets and then enhance contacts and innervation surfaces for functional amelioration.
Schematic representation of cell-based reconstructive approach to volumetric muscle loss (VML) recovery.
However, the translation of tissue engineering strategies to clinical practice is still a challenging task. In particular, there are three main limitations to overcome: (i) finding the optimal muscle progenitor source that show both myogenic potential and high proliferation rates to obtain a sufficient amount of cells; (ii) achieving a 3D tissue with an adequate density, dimensions and cell alignment to be comparable with a native muscle tissue architecture; (iii) promoting the in vivo integration and survival of an implanted tissue through rapid vascularization and innervation