Evaluation of biological sex on endstage pathobiology and regenerative treatment of volumetric muscle loss

Volumetric muscle loss (VML) is a severe injury resulting in substantial skeletal muscle loss, leading to a complex pathology that culminates in suboptimal tissue repair and significant long-term functional deficits. This study employs a rodent model of VML to investigate the impact of biological sex on the injury pathobiology and its potential influence on the response to autologous minced muscle grafting (MMG) as a regenerative therapy. While no significant differences were observed between the end-stage male and female responses to VML, both male and female subjects appeared to benefit from MMG treatment. Females demonstrated improved neuromuscular function, while males exhibited reduced fibrosis at the site of injury. Additional differences in the wound healing response included distinct variations in myofiber characteristics, with females exhibiting a lower proportion of Type 2a fibers and elevated levels of myogenin. These findings suggest that regenerative therapies, such as MMG, may exhibit sex-specific benefits. Future studies will further explore sexual dimorphism in the acute response to injury to identify potential therapeutic targets that may yield greater therapeutic efficacy for each sex.