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



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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.