The objective of this study was to determine whether donor muscle age influences structural and functional recovery following transplantation into a volumetric muscle loss (VML) injury. We hypothesized that juvenile skeletal muscle, with its higher satellite cell content and enhanced myogenic potential, would yield superior regenerative and functional outcomes compared to adult muscle when used as a transplant source. Methods: Male Lewis rats received full thickness VML injuries to the tibialis anterior (TA) muscle, followed by transplantation of minced juvenile or adult muscle tissue from ubiquitous green fluorescent protein (GFP) rats, or no treatment. Prior to transplantation, donor muscles were analyzed for myofiber morphology, satellite cell density, and primary myoblast behavior in culture. Seven weeks after transplantation, functional recovery was measured by stimulating the peroneal nerve to elicit maximal TA contraction (mN·m), this was followed by histological assessment of GFP + fiber integration, cross-sectional area (CSA, µm 2 ), and satellite cell distribution. Results: Juvenile donor muscle contained ~15-fold more satellite cells per square millimeter than adult tissue and demonstrated greater myotube formation in vitro (+60–80% MyHC + area). In vivo, both donor ages increased peak torque by 36–50% relative to untreated VML, restored myofiber number to control levels, and produced comparable percentages of GFP + integrated donor fibers (~11–13% TA CSA). However, all VML groups exhibited persistently small myofiber CSA (< 1,400 µm 2 vs. 2,569 ± 334 µm 2 in controls), and no significant functional differences emerged between juvenile and adult recipients. Satellite cell density increased substantially within the transplant area for both donor ages, and juvenile recipients showed slightly higher proportions of centralized nuclei, indicating active regeneration but limited hypertrophy. Conclusion: juvenile skeletal muscle possesses clear cellular advantages ex vivo, yet these intrinsic benefits did not translate into superior short-term functional recovery following transplantation. Both donor ages partially restored muscle architecture and strength, suggesting that additional biological or rehabilitative stimuli may be required to unlock the full regenerative potential of transplanted tissue. This work underscores the importance of donor characteristics while also highlighting the constraints imposed by the VML injury environment. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Payne et al. (Fri,) studied this question.