High intensity resistance training induced angiogenesis and muscle hypertrophy enhance skeletal muscle regeneration in volumetric muscle loss rats

Skeletal muscle has an outstanding regenerative capacity when damaged muscle mass is less than 20%. The volumetric muscle loss (VML) injury, muscle loss beyond self-repair capacity, results in functional and morphological disability. This study investigated the effect of myofibers injection into a decellurized extracellular matrix (ECM) with resistance training on skeletal muscle growth following a VML injury. Male fisher 344 and 2 month old F344-Tg (UBC-EGFP) rats, as myofiber donors, were used in this study. Approximately 20% of the mass of the lateral gastrocnemius (LGAS) was excised, which was replaced by ECM in same dimensions. 30 myofibers were injected into the injury site in 7 days of post injury, Ladder climbing began at 10 days post defect surgery, and rats were subjected to climb a ladder every third day with weight for 6 weeks. Following 56 days of recovery, EXE group (5122±92μm2) increased cross sectional area of intact muscle area significantly compared to ECM (4668±79μm2), FIB (4795±82μm2), and FIB+EXE (47642±97μm2) groups. Quantification of the number of blood vessel larger than 20μm in the entire area showed a significant difference only in EXE group (46±4.2) compared to ECM group (35±3.89). EXE group (34±3.2) significantly increased the number of blood vessel compared to ECM group (22±3.3). A significant difference in connective tissue area in middle region of the ECM was quantified between EXE (45±1.6%) and ECM (69±1.9%) groups (Figure 10). Moreover, small muscle fiber area within ECM was significantly higher in EXE group (1.39±30.15 μm2) than ECM and FIB groups (0.67±0.15μm2). The data suggest that ECM transplantation with resistance training can repair a volumetric muscle loss injury by hypertrophy, angiogenesis, and myofiber infiltration through entire ECM regions.