Recovery from volumetric muscle loss injury: A comparison between young and aged rats

• Comparison between young and aged rats to volumetric muscle loss injury (VML).
• Age does not exacerbate the post-VML functional response.
• Age affects ECM composition and results in a more fibrotic post-VML environment.

Termed volumetric muscle loss (VML), the bulk loss of skeletal muscle tissue either through trauma or surgery overwhelms the capacity for repair, leading to the formation of non-contractile scar tissue. The myogenic potential, along with other factors that influence wound repair are known to decline with age. In order to develop effective treatment strategies for VML injuries that are effective across a broad range of patient populations, it is necessary to understand how the response to VML injury is affected by aging. Towards this end, this study was conducted to compare the response of young and aged animal groups to a lower extremity VML injury. Young (3 months, n = 12) and aged (18 months, n = 8) male Fischer 344 rats underwent surgical VML injury of the tibialis anterior muscle. Three months after VML injury it was found that young TA muscle was on average 16% heavier than aged muscle when no VML injury was performed and 25% heavier when comparing VML treated young and aged animals (p < 0.0001, p < 0.0001). Peak contractile force for both the young and aged groups was found to decrease significantly following VML injury, producing 65% and 59% of the contralateral limbs' peak force, respectively (p < 0.0001). However, there were no differences found for peak contractile force based on age, suggesting that VML affects muscle's ability to repair, regardless of age. In this study, we used the ratio of collagen I to MyoD expression as a metric for fibrosis vs. myogenesis. Decreasing fiber cross-sectional area with advancing age (p < 0.005) coupled with the ratio of collagen I to MyoD expression, which increased with age, supports the thought that regeneration is impaired in the aged population in favor of fibrosis (p = 0.0241). This impairment is also exacerbated by the contribution of VML injury, where a 77-fold increase in the ratio of collagen I to MyoD was observed in the aged group (p < 0.0002). The aged animal model described in this study provides a tool for investigators exploring not only the development of VML injury strategies but also the effect of aging on muscle regeneration.