The effect of autologous repair and voluntary wheel running on force recovery in a rat model of volumetric muscle loss.

Abstract

What is the central question of this study? Following large traumatic loss of muscle tissue (volumetric muscle loss; VML), permanent functional and cosmetic deficits present themselves and regenerative therapies alone have not been able to generate a robust regenerative response: how does the addition of rehabilitative therapies affects the regenerative response? What is the main finding and its importance? Using exercise along with autologous muscle repair, we demonstrated accelerated muscle force recovery response post-VML. The accentuated force recovery 2weeks post-VML would allow patients to return home sooner than allowed with current therapies. Skeletal muscle can regenerate from damage but is overwhelmed with extreme tissue loss, known as volumetric muscle loss (VML). Patients suffering from VML do not fully recover force output in the affected limb. Recent studies show that replacement tissue (i.e., autograph) into the VML defect site plus physical activity show promise for optimizing force recovery post-VML. The purpose of this study was to measure the effects of autologous repair and voluntary wheel running on force recovery post-VML. Thirty-two male Sprague-Dawley rats had 20% of their left tibialis anterior (LTA) excised then replaced and sutured into the intact muscle (autologous repair). The right tibialis anterior (RTA) acted as the contralateral control. Sixteen rats were given free access to a running wheel (Wheel) whereas the other 16 remained in a cage with the running wheel locked (Sed). At 2 and 8weeks post-VML, the LTA underwent force testing; then the muscle was removed and morphological and gene expression analysis was conducted. At 2weeks post-injury, normalized LTA force was 58% greater in the Wheel group compared to the Sed group. At 8weeks post-VML, LTA force was similar between the Wheel and Sed groups but was still lower than the uninjured RTA. Gene expression analysis at 2weeks post-VML showed the wheel groups had lower mRNA content of interleukin (IL)-1β, IL-6 and tumour necrosis factor α compared to the Sed group. Overall, voluntary wheel running promoted early force recovery, but was not sufficient to fully restore force. The accentuated early force recovery is possibly due to a more pro-regenerative microenvironment.