Current standard of care for VML is typically based on surgicalinterventionwithautologousmusclegraftandphysical therapy. Further clinically used strategies include acupunctureandapplicationofscaffolds. 2.1.SurgicalTechniques. SurgicaltreatmentforVMLincludes mainlyscartissuedebridementand/ormuscletransposition [33]. Autologous muscle transfer is commonly performed in a clinical situation, when there are large areas of muscle loss following trauma, tumor resection, or nerve injury, whichimpairstheirreplaceablemotorfunction[34,35].The surgeonsgrafthealthymusclefromadonorsiteunaffectedby theinjurytorestorethelostorimpairedfunction[36].When no adjacent muscle is available because of high-level nerve injuriesorseveretrauma,autologousmuscletransplantation together with neurorrhaphy, in the form of free functional muscle transfer, can be applied [37, 38]. The most popular autologous muscles are latissimus dorsi muscle and gracilis muscle. Latissimus dorsi muscle transfer has been shown to be safe and efficient for restoration of elbow flexion after injuries [34]. In the case of a synovial sarcoma affecting the right gluteus medius and minimus muscles, the function of theaffectedhipabductioncouldbefullyreconstructedwith
a free neurovascularlatissimus dorsi muscle transplantation [39]. Free gracilis muscle transfer is commonly utilized to restoreelbowflexionafterpan-brachialplexusinjury[40].It isalsoappliedformuscleweaknessafterfacialpalsyorpelvic floor reconstruction [41, 42]. Although functional muscle flapscanleadtoatleastdecentfunctionalresults,theycause substantialdonorsitemorbidityandinadequateinnervation [43]. Moreover, as many as 10% of these reconstructive surgeriesresultincompletegraftfailureduetocomplications suchasinfectionandnecrosis[44].Sometimes,thesourceof autologousmusclesforgraftingisaproblem,ifthepatientis severelyinjured. 2.2. Physical Therapy. Exercise has the ability to prevent a decreaseofskeletalmusclemass[45].Thus,inadditiontosurgicaltechniques,physicaltherapyisanoninvasive/minimally invasive way to promote muscle tissue repair and regeneration. It is especially used for rehabilitationafter injuries and muscletissuetransfer,ortotreatchronicmuscleloss. Physicalrehabilitationaimsatstrengtheningtheremaining muscles. This has been shown to accelerate muscle healing/regeneration by modulating the immune response, release of growth factors, promoting vascularization, and reducing scar formation [46–48]. Functional performance of nonrepaired VML injured muscle could be significantly improved with physical rehabilitation in the form of voluntarywheelrunning[49].Interventionstoenhanceangiogenesis including exercise and massage are potential strategies toacceleratenewmuscleformationinclinicallytransplanted muscle grafts or other surgical situations [50]. It has been reported that physical exercise can upregulate the IGF-1 signaling pathway and decrease myostatin in muscle tissue ofanimalsandhumans,thuspreventingmuscleatrophy[51– 53].
Physical therapy can indeed improve muscle repair and recovery;however,itisunabletofacilitatesubstantialmuscle regeneration within the defect areas in VML. In addition, patientswithseverediseasesorinjuriesarefrequentlyunable tomakeconsistentexercise,whichlimitsphysicaltherapyas atreatmentforVML