Abstract
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.
Similar content being viewed by others
References
Corona BT, Wenke JC, Ward CL. Pathophysiology of volumetric muscle loss injury. Cells Tissues Organs. 2016;202(3–4):180–8.
Garg K, Ward CL, Hurtgen BJ, Wilken JM, Stinner DJ, Wenke JC, et al. Volumetric muscle loss: persistent functional deficits beyond frank loss of tissue. J Orthop Res, 33s. 2015;33:40–6.
Anderson SE, et al. Determination of a critical size threshold for volumetric muscle loss in the mouse quadriceps. Tissue Eng Part C Methods. 2019;25(2):58–70.
Turner NJ, Badylak SF. Regeneration of skeletal muscle. Cell Tissue Res. 2012;347:759–74.
VanDusen KW, Syverud BC, Williams ML, Lee JD, Larkin LM. Engineered skeletal muscle units for repair of volumetric muscle loss in the tibialis anterior muscle of a rat. Tissue Eng Part A. 2014;20(21–22):2920–30.
Rodriguez BL, et al. The maturation of tissue-engineered skeletal muscle units following 28-day ectopic implantation in a rat. Regen Eng Transl Med. 2018;4:1–9.
Mertens JP, Sugg KB, Lee JD, Larkin LM. Engineering muscle constructs for the creation of functional engineered musculoskeletal tissue. Regen Med. 2014;9(1):89–100.
Aguilar CA, Greising SM, Watts A, Goldman SM, Peragallo C, Zook C, et al. Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury. Cell Death Dis. 2018;4:33.
Wu X, Corona BT, Chen X, Walters TJ. A standardized rat model of volumetric muscle loss injury for the development of tissue engineering therapies. Biores Open Access. 2012;1(16):280–90.
National Research Council. Guide for the care and use of laboratory animals. Washington D.C: The National Academies Press; 2011.
Syverud BC, Gumucio JP, Rodriguez BL, Wroblewski OM, Florida SE, Mendias CL, et al. A transgenic tdTomato rat for cell migration and tissue engineering applications. Tissue Eng Part C Methods. 2018;24(5):263–71.
Larkin LM, Davis CS, Sims-Robinson C, Kostrominova TY, Remmen HV, Richardson A, et al. Skeletal muscle weakness due to deficiency of CuZn-superoxide dismutase is associated with loss of functional innervation. Am J Phys Regul Integr Comp Phys. 2011;301:R1400–7.
Burkholder TJ, Fingado B, Baron S, Lieber RL. Relationship between muscle fiber types and sizes and muscle architectural in the mouse hindlimb. J Morphol. 1994;221:177–90.
Edgar Erdfelder, Franz Faul, Axel Buchner. GPOWER: A general power analysis program. Behav Res Methods Instrum Comput. 1996;28(1):1–11
Acknowledgments
The authors would like to acknowledge Margaret Hogan, Alexander Wood, and Matthew Nguyen for their technical support and recommendations.
Funding
This study received funding from NIH/NIAMS 1R01AR067744-01.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Vega-Soto, E.E., Rodriguez, B.L., Armstrong, R.E. et al. A 30% Volumetric Muscle Loss Does Not Result in Sustained Functional Deficits After a 90-Day Recovery in Rats. Regen. Eng. Transl. Med. 6, 62–68 (2020). https://doi.org/10.1007/s40883-019-00117-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40883-019-00117-2