The frank loss of a large volume of skeletal muscle (i.e., volumetric muscle loss; VML) can lead to functional debilitation and presents a significant problem to civilian and military medicine.....In the current study, we further extend our recent progress.....in the development of tissue engineered muscle repair (TEMR) constructs (i.e., muscle derived cells (MDCs) seeded on a bladder acellular matrix (BAM) preconditioned with uniaxial mechanical strain) for the treatment of VML. TEMR constructs were implanted into a VML defect in a tibialis anterior muscle of Lewis rats and observed out to 12 weeks post-injury. The salient findings of the study were: 1) TEMR constructs exhibited a highly variable capacity to restore in vivo function of injured TA muscles, wherein TEMR positive responders (n = 6) promoted a ≈61% improvement but negative responders (n = 7) resulted in no improvement compared to non-repaired controls, 2) TEMR positive and negative responders exhibited differential immune responses that may underlie these variant responses, 3) BAM scaffolds (n = 7) without cells promoted an ≈26% functional improvement compared to uninjured muscles, 4) TEMR positive responders promoted muscle fiber regeneration within the initial defect area while BAM scaffolds did so only sparingly. These findings indicate that TEMR constructs can improve the in vivo functional capacity of the injured musculature at least in part by promoting generation of functional skeletal muscle fibers. In short, the degree of functional recovery observed following TEMR implantation (BAM + MDCs) was 2.3X-fold greater than that observed following implantation of BAM alone. As such, underscores the potential benefits of including a cellular component in the tissue engineering strategy for VML injury.