A 30% Volumetric Muscle Loss Does Not Result in Sustained Functional Deficits After a 90-Day Recovery in Rats

Volumetric muscle loss (VML) is defined as the loss of skeletal muscle tissue which exceeds the body’s repair capabilities leading to sustained functional deficits over time. Some etiologies leading to VML include traumatic injuries, congenital diseases, and degenerative myopathies. Currently, the lack of standardized animal models prevents an appropriate estimation of the severity of injury capable of exceeding self-regeneration. Recent work in our laboratory has shown that a 30% VML does not create a sustained functional loss in rats after 3 months. Therefore, the purpose of this study was to evaluate the percentage threshold of muscle loss that results in permanent functional deficits. We surgically created models of 30, 40, and 50% VML injuries in the tibialis anterior (TA) of rats, and subsequently evaluated TA function and structure after a 90-day recovery period. TA muscle force production was measured in situ by stimulating the sciatic nerve to obtain a maximum tetanic force. Results revealed that the maximum force produced by rats with a 30% VML was not significantly different from the uninjured muscle, while the maximum force of the 40% and 50% VML groups was significantly lower in comparison to the uninjured muscle. Overall, this study further supports our observations, suggesting that a 30% VML rat model is not suitable for VML studies. Thus, increasing VML percentages might provide an improved standardized and clinically relevant model for VML that produces a long-term deficit in muscle self-regeneration, while providing a strong base for future tissue engineering techniques in medicine. Lay Summary The lack of a standardized animal model limits studies addressing volumetric muscle loss. Previous work in our laboratory has shown that a loss of 30% muscle mass does not create a prolonged deficit in the muscle’s functional properties. Thus, the purpose of this study was to determine the percentage of muscle loss necessary to produce a long-term deficit in the functional properties of the injured muscle. Our results suggest that a minimum of 40% muscle loss is needed to produce a significant sustained deficit in muscle force production. Future work in rats will involve the use of a 40% or more VML injury. We will focus on addressing these larger VML injuries by implanting engineered muscle tissue into the injury site to restore muscle function to pre-injury levels.